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 and safety of automatic pressure-controlled pressure cupping in patients with lumbar disc herniation, and compare it with traditional cupping. METHODS: A total of 100 patients diagnosed with lumbar disc herniation from January 2022 to August 2024 were selected and divided into two groups:the automatic pressure-controlled pressure cupping group (controlled pressure cupping group) and the traditional cupping group (control group), 50 cases in each group. In the controlled pressure cupping group, there were 18 males and 32 females, with an age of (51.98±12.69) years;in the control group, there were 16 males and 34 females, with an age of (51.32±12.05) years. The visual analogue scale(VAS), comfort score, and lumbar range of motion were observed before treatment and after the 1st, 3rd, and 7th treatments to evaluate the efficacy and safety. RESULTS: All patients completed the treatment intervention, with complete follow-up data collected. No adverse reactions or complications occurred during treatment and follow-up. After the 3rd treatment, the VAS score of the controlled pressure cupping group was (2.38±0.49), which was lower than that of the control group (2.94±0.68), with a statistically significant difference (P<0.001). In the controlled pressure cupping group, the VAS scores after the 1st, 3rd, and 7th treatments were significantly better than those before treatment (P=0.026);in the control group, the VAS scores after the 3rd and 7th treatments were better than those before treatment, but the difference was not statistically significant(P=0.182). Repeated-measures analysis of variance (ANOVA) on VAS scores at different time points in both groups showed that there were statistically significant differences in inter-group, time, and interaction effects (P<0.05). After the 1st treatment, in the controlled pressure cupping group, 0 patients felt comfortable, 42 patients (84%) felt mild discomfort, and 8 patients (16%) felt moderate discomfort;in the control group, 0 patients felt comfortable, 28 patients (56%) felt mild discomfort, and 22 patients(44%) felt moderate discomfort;the difference between the two groups was statistically significant(P=0.005). After the 3rd treatment, in the controlled pressure cupping group, 30 patients(60%) felt comfortable, 20 patients (40%) felt mild discomfort, and 0 patients felt moderate discomfort; in the control group, 9 patients (18%) felt comfortable, 41 patients (82%) felt mild discomfort, and 0 patients felt moderate discomfort;the difference between the two groups was statistically significant(P<0.001). There was no statistically significant difference in comfort between the two groups after the 7th treatment(P>0.001). There was no statistically significant difference in lumbar range of motion between the two groups before and after treatment(P>0.05);compared with before treatment, the lumbar range of motion of both groups after treatment was significantly improved, with statistically significant differences (P<0.001). CONCLUSION Automatic pressure-controlled pressure cupping can effectively relieve symptoms in patients with lumbar disc herniation, with excellent safety.
Humans ; Female ; Male ; Intervertebral Disc Displacement/physiopathology* ; Middle Aged ; Adult ; Lumbar Vertebrae/physiopathology* ; Cupping Therapy/methods* ; Pressure ; Aged ; Treatment Outcome

OBJECTIVE: To investigate the effects of thymoquinone on the proliferation of acute myeloid leukemia (AML) cells and its molecular mechanism, so as to provide theoretical basis for the basic research on the anti-leukemia of traditional Chinese medicine. METHODS: The HL-60 and THP-1 cells were treated with thymoquinone at different concentration gradients, cell proliferation was detected by CCK-8 method, morphological changes were detected by Wright-Giemsa method, apoptosis was detected by Annexin V/PI double staining flow cytometry, and apoptosis and signal pathway protein expression were detected by Western blot. Real-time quantitative fluorescence PCR and Western blot were used to detect the expression changes of high mobility family members of SRY-related proteins (SOX). RESULTS: Thymoquinone inhibited the malignant proliferation of HL-60 and THP-1 cells, up-regulated the expression of pro-apoptotic protein Bax, down-regulated the expression of anti-apoptotic protein Bcl-2 and Survivin, and hydrolyzed Caspase-3 to induce the apoptosis of HL-60 and THP-1 cells. Thymoquinone could also significantly down-regulate the phosphorylation of PI3K, Akt and mTOR, and inhibit the malignant biological characteristics of HL-60 and THP-1 cells by inhibiting the activation of PI3K/Akt/mTOR pathway. After thymoquinone intervention in HL-60 and THP-1 cells, the expression of SOX2 and SOX4 could be down-regulated significantly. At low concentration ( < 10 μmol/L), the expression of SOX12 was weakly affected by thymoquinone. With increasing concentration, the expression of SOX12 could be down-regulated, however, thymoquinone had no effect on SOX11 expression. CONCLUSION Thymoquinone can inhibit the proliferation of AML cells, and its mechanism may be related to inhibiting the activation of PI3K/Akt/mTOR signaling pathway, regulating the expression of apoptotic proteins and core members of SOX family.
Humans ; Benzoquinones/pharmacology* ; Cell Proliferation/drug effects* ; Leukemia, Myeloid, Acute/metabolism* ; Apoptosis/drug effects* ; HL-60 Cells ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; bcl-2-Associated X Protein/metabolism* ; Cell Line, Tumor ; Phosphatidylinositol 3-Kinases/metabolism* ; THP-1 Cells

BACKGROUND:Osteochondral defect of the joint is a difficult problem faced by orthopedic surgeons,and traditional repair methods are difficult to obtain satisfactory curative effects.Hydroxyapatite-polyvinyl alcohol-based composite hydrogel material is a direction of current research. OBJECTIVE:To prepare hydroxyapatite-polyvinyl alcohol/collagen-chitosan-gelatin composite hydrogel material and characterize its physical characteristics,to verify its histocompatibility and cell adhesion and proliferation ability after implantation in vivo,and explore its repair effect on rabbit osteochondral defects. METHODS:The cylindrical porous poly(lactic acid)scaffold was prepared by 3D printing technology(the pore sizes were 1.2,1.4,1.6 and 1.8 mm,respectively).The poly(lactic acid)scaffold was injected with polyvinyl alcohol and hydroxyapatite mixed emulsion.After freezing thawing and dichloromethane dissolution,hydroxyapatite-polyvinyl alcohol hydrogel was prepared.Then,the collagen-chitosan-gelatin mixture was injected into the hydroxyapatite-polyvinyl alcohol hydrogel and crosslinked with genipin.Finally,the hydroxyapatite-polyvinyl alcohol/collagen-chitosan-gelatin composite hydrogel was prepared by alcohol cleaning and freeze-drying.The physical characteristics of the four groups of hydrogels were characterized,and the hydrogels with the best performance were screened for follow-up experiments.Hydroxyapatite-polyvinyl alcohol hydrogel and collagen-chitosan-gelatin composite hydrogel were implanted subcutaneously in SD rats.Hematoxylin-eosin staining and Masson staining were used to observe the adhesion growth of cells on the material surface.Osteochondral defect(diameter:5 mm,depth:6 mm)models were made in the femoral trochlea of bilateral knee joints of 15 rabbits.The composite hydrogel was implanted on the left side(experimental group),while no material was implanted on the right side(control group).Micro-CT and histology were used to evaluate the repair effect of osteochondral defects. RESULTS AND CONCLUSION:(1)Based on the results of porosity,water content,mechanical testing and scanning electron microscopy,it was concluded that the hydroxyapatite-polyvinyl alcohol/collagen-chitosan-gelatin composite hydrogel with a pore size of 1.2 mm was more consistent with the general characteristics of natural cartilage,which was used for subsequent experiments.(2)Hematoxylin-eosin staining and Masson staining exhibited that with the extension of subcutaneous implantation time of the materials,the adhesion of cells around the two materials increased significantly,and the proliferation of cells after the implantation of collagen-chitosan-gelatin was better,a large number of cells could be seen growing into the formed network structure,and the network structure was gradually degraded.(3)In the rabbit osteochondral defect experiment,8 weeks after surgery,Micro-CT examination demonstrated that the material implanted in the experimental group had good integration with the surrounding bone-cartilage,with some bone growth on the surface and inside,while the cartilage and subcartilage in the control group still had obvious defects,without effective repair.Hematoxylin-eosin staining and toluidine blue staining displayed that the composite hydrogel in the experimental group integrated with the surrounding articular cartilage 4-8 weeks after implantation.With the extension of time,new cartilage gradually formed on the surface of the material.At 12 weeks,most of the defect was covered by new cartilage,and good bone growth was also observed in the subcartilage.In the control group,the deep bone defects were mostly repaired and the superficial cartilage and subchondral bone defects were also repaired to a certain extent,but they were mainly replaced by fibrous tissue and part of fibrocartilage 12 weeks after surgery.(4)In conclusion,hydroxyapatite-polyvinyl alcohol/collagen-chitosan-gelatin composite hydrogel material can mimic the structure and function of natural cartilage,and can effectively repair osteochondral defects in animal experiments.

Objective To build the early predictive model for chronic kidney disease(CKD)in hypertension and diabetes patients in the community.Methods The CKD patients were recruited from 4 health care centers in 4 urban areas in Kunming.The control group was residents without hypertension and diabetes(n = 1267).The disease group was residents with hypertension and/or diabetes(n = 566).The questionnaire survey,physical examination,laboratory testing,and 5 SNPs gene types in the PVT1 gene.The risk factors,which were filtered with logistics regression,were used to build predictive models.Four machine learning algorithms were built:support vector machine(SVM),random forest(RF),Na?ve Bayes(NB),and artificial neural network(ANN)models.Results Thirteen indicators included in the final diagnostic model:age,disease type,ethnicity,blood urea nitrogen,creatinine,eGFR from MDRD,ACR,eGFR from EPI2009,PAM13 score,sleep quality survey,staying-up late,PVT1 SNP rs11993333 and rs2720659.The accuracy,specificity,Kappa value,AUC of ROC,and PRC of ANN are greater than those of the other 3 models.The sensitivity of RF is the highest among 4 types of machine learning.Conclusions The ANN predictive model has a good ability of efficiency and classification to predict CKD with hypertension and/or diabetes patients in the community.

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 monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

Objective To investigate the therapeutic effect of Xuebijing on anti-N-methyl-D-aspartate receptor(NMDAR)encephalitis mice and its effect on the changes of helper T cell 1(Th1)/helper T cell 2(Th2).Methods The experimental groups included control group,model group,low-dose Xuebijing(low-XBJ)group,high-dose Xuebijing(high-XBJ)group,with 10 mice in each group,except the control group,the other 3 groups of mice were treated with antigen injection and immune stimulation to establish anti-NMDAR encephalitis models,the mice in the low-XBJ and high-XBJ groups were intraperitoneally injected with 5 ml/kg and 10 ml/kg of Xuebijing injection,respectively,once every 12 hours for 3 consecutive days;After 2 weeks,HE staining was used to observe the pathological changes of mice brain tissue,Nissl staining was used to observe the morphological changes of mice neurons,TUNEL staining was used to detect the apoptosis of mice neurons,ELISA was used to detect the contents of tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,IL-4 and interferon-γ(IFN-γ)in serum and cerebrospinal fluid of mice,immunohistochemical staining and Western blotting were used to detect the expression of IFN-γ and IL-4 in brain tissue,flow cytometry was used to detect the distribution of Th1 and Th2 cells in peripheral blood,and the ratio of Th1/Th2 was calculated.Results Compared with the model group,hippocampal tissue damage was improved in low-XBJ group and high-XBJ group,the morphological changes of neurons were small,the morphology of Nissl bodies was more complete and the number of Nissl bodies was increased,the TUNEL positive rate of neurons decreased,the contents of TNF-α,IL-1β and IFN-γ in serum and cerebrospinal fluid decreased while the content of IL-4 increased,the percentage of IFN-γ positive cells and the relative expression of protein in brain tissue decreased,the percentage of IL-4 positive cells and the relative expression of protein increased,the proportion of cluster of differentiation(CD)4+IFN-γ+labeled Th1 cells and the ratio of Th1/Th2 in peripheral blood decreased,and the proportion of CD4+IL-4+labeled Th2 cells in peripheral blood of mice in high-XBJ group increased,the differences were statistically significant(P＜0.05).In addition,compared with the low-XBJ group,the improvement effect of the above detection indicators in the high-XBJ group was more obvious,and the differences were statistically significant(P＜0.05).Conclusion Xuebijing can improve hippocampal neuronal damage in anti-NMDAR encephalitis mice,which may play a therapeutic role by reducing the expression of IFN-γ,promoting the expression of IL-4 and maintaining the balance of Th1/Th2 cells.

Aim To clarify the anti-rheumatoid arthritis effect of Tibetan medicine Pulicaria insignis (P. insignis),sift out the active parts against rheumatoid arthritis,and investigate the mechanism. Methods Rat rheumatoid arthritis (CIA) model was established with bovine type II collagen and incomplete Freund's adjuvant. The effects of the total extract of P. insignis, macroporous resin eluted parts with different concentrations of ethanol and Tripterygium Glycosides (GTW) on the degree of foot swelling in CIA rats were observed,the levels of tumor necrosis factor (TNF-α), intd rheumaerleukin-1β (IL-1β) antoid factor (RF) in serum of rats were detected, the pathological changes of synovial tissues were investigated, and the effects on MAPK/p38/NF-κB, TLR4/NF-κB protein expressions were explored by Western blot. Results Compared with the model group, the total extract of P. insignis and the eluted part of macroporous resin 60% ethanol could significantly reduce the degree of joint swelling in CIA rats, effectively improve the pathological changes of rats synovium tissues, and significantly reduce the levels of rat tumor necrosis factor (TNF-α), interleukin-1β (IL-1β) and rheumatoid factor (RF) in serum inflammatory factors, and markedly decrease the expression of related inflammatory proteins (TLR4, NF-κB, Myd88, p-p38, p-IκBα, iNOS, etc) in synovial tissue. Conclusions (1) P. insignis can relieve the symptoms of joint inflammation in rats with rheumatoid arthritis, and the eluted part of macroporous resin 60% ethanol of P. insignis is the effective active part for anti-rheumatoid arthritis. (2) The total and partial extracts of P. insignis can relieve arthritis symptoms in CIA rats through inhibiting the MAPK/ p38/NF-κB and TLR4/NF-κB signaling pathways.

BACKGROUND: Patients with mass-forming pancreatitis (MFP) or pancreatic ductal adenocarcinoma (PDAC) presented similar clinical symptoms, but required different treatment approaches and had different survival outcomes. This meta-analysis aimed to compare the diagnostic performance of contrast-enhanced ultrasound (CEUS) and contrast-enhanced computed tomography (CECT) in differentiating MFP from PDAC. METHODS: A literature search was performed in the PubMed, EMBASE (Ovid), Cochrane Library (CENTRAL), China National Knowledge Infrastructure (CNKI), Weipu (VIP), and WanFang databases to identify original studies published from inception to August 20, 2021. Studies reporting the diagnostic performances of CEUS and CECT for differentiating MFP from PDAC were included. The meta-analysis was performed with Stata 15.0 software. The outcomes included the pooled sensitivity, specificity, positive likelihood ratio (+LR), negative likelihood ratio (-LR), diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) curves of CEUS and CECT. Meta-regression was conducted to investigate heterogeneity. Bayesian network meta-analysis was conducted to indirectly compare the overall diagnostic performance. RESULTS: Twenty-six studies with 2115 pancreatic masses were included. The pooled sensitivity and specificity of CEUS for MFP were 82% (95% confidence interval [CI], 73%-88%; I2  = 0.00%) and 95% (95% CI, 90%-97%; I2  = 63.44%), respectively; the overall +LR, -LR, and DOR values were 15.12 (95% CI, 7.61-30.01), 0.19 (95% CI, 0.13-0.29), and 78.91 (95% CI, 30.94-201.27), respectively; and the area under the SROC curve (AUC) was 0.90 (95% CI, 0.87-92). However, the overall sensitivity and specificity of CECT were 81% (95% CI, 75-85%; I2  = 66.37%) and 94% (95% CI, 90-96%; I2  = 74.87%); the overall +LR, -LR, and DOR values were 12.91 (95% CI, 7.86-21.20), 0.21 (95% CI, 0.16-0.27), and 62.53 (95% CI, 34.45-113.51), respectively; and, the SROC AUC was 0.92 (95% CI, 0.90-0.94). The overall diagnostic accuracy of CEUS was comparable to that of CECT for the differential diagnosis of MFP and PDAC (relative DOR 1.26, 95% CI [0.42-3.83], P  > 0.05). CONCLUSIONS CEUS and CECT have comparable diagnostic performance for differentiating MFP from PDAC, and should be considered as mutually complementary diagnostic tools for suspected focal pancreatic lesions.
Humans ; Contrast Media ; Bayes Theorem ; Tomography, X-Ray Computed/methods* ; Pancreatic Neoplasms/diagnostic imaging* ; Carcinoma, Pancreatic Ductal/diagnostic imaging* ; Sensitivity and Specificity ; Pancreatitis/diagnostic imaging* ; Ultrasonography/methods*