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Objective To investigate the effects of Fuzheng Quxie Prescription(mainly with the actions of supporting healthy qi and dispelling pathogens)combined with neoadjuvant chemotherapy on tumor recurrence,serum thymidine kinase 1(TK1)level and immune function in patients with triple-negative breast cancer(TNBC).Methods Eighty patients with TNBC of qi and yin deficiency type were randomly divided into a combination group and a control group,with 40 patients in each group.The control group was treated with AC-T sequential chemotherapy(Doxorubicin combined with Cyclophosphamide plus sequential Docetaxel),and the combination group was treated with Fuzheng Quxie Prescription on the basis of treatment for the control group.One course of treatment covered 21 days,and the two groups were treated for 4 consecutive courses.The changes of traditional Chinese medicine(TCM)syndrome scores,Karnofsky Performance Status(KPS)score,levels of tumor markers of carbohydrate antigen 125(CA125),carbohydrate antigen 153(CA153)and TK1,and T lymphocyte subset levels in the two groups were observed before and after the treatment.Moreover,the clinical efficacy and tumor metastasis and recurrence in the two groups were compared.Results(1)After 4 courses of treatment,the total effective rate of the combination group was 87.50%(35/40),and that of the control group was 67.50%(27/40),and the intergroup comparison(tested by chi-square test)showed that the efficacy of the combination group was significantly superior to that of the control group(P＜0.05).(2)After treatment,the TCM syndrome scores in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the KPS scores were significantly increased compared with those before treatment(P＜0.05),and the decrease of TCM syndrome scores and the increase of KPS scores in the combination group were significantly superior to that in the control group(P＜0.05 or P＜0.01).(3)After treatment,the serum CA125,CA153 and TK1 levels of patients in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease of serum CA125,CA153 and TK1 levels in the combination group was significantly superior to that in the control group(P＜0.01).(4)After treatment,the T lymphocyte subset CD3+,CD4+ levels and CD4+/CD8+ ratio in the two groups were significantly increased compared with those before treatment(P＜0.05),and the CD8+ level was significantly decreased compared with that before treatment(P＜0.05).The post-treatment intergroup comparison showed that the increase of the T lymphocyte subset CD3+,CD4+ levels and CD4+/CD8+ ratio as well as the decrease of the CD8+ level in the combination group was all significantly superior to that in the control group(P＜0.05 or P＜0.01).(5)The one-year follow-up showed that the tumor recurrence rate and tumor metastasis rate in the combination group were 7.50%(3/40)and 12.50%(5/40)respectively,significantly lower than 25.00%(10/40)and 35.00%(14/40)in the control group,and the differences were statistically significant when comparing between the two groups(P＜0.05).Conclusion The combination of neoadjuvant chemotherapy with Fuzheng Quxie Prescription has a better therapeutic effect on TNBC patients with qi and yin deficiency syndrome,which can effectively improve the immune function of the patients,decrease the level of serum tumor markers,improve the quality of life of the patients,and reduce the incidence of tumor recurrence and metastasis.
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Biological toxins are toxic molecules produced by specific microorganisms,plants or animals.Due to their wide range of sources and high toxicity,the availability of protein and non-protein toxins is becoming increasingly important,some of which are used for military purposes and developed as biotoxin warfare agents.In this paper,the classification and mechanism of action of biological toxins are discussed.In addition,the strategies for prevention and control of biological toxins as well as their therapeutic applications are reviewed.
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Objective To investigate the clinical characteristics and risk factors of thyroid dysfunction(TD)in malignant tumor patients treated with immune checkpoint inhibitors(ICIs).Methods A total of 157 cancer patients who were hospitalized and received ICIs treatment in the First People's Hospital of Yunnan Province from January 2019 to June 2022 were collected and divided into the normal thyroid function group and abnormal thyroid function group based on whether TD had occurred.Fifty-eight patients with the normal thyroid function and 58 patients with the abnormal thyroid function were selected,and 58 healthy adults who underwent the physical examination in our hospital were randomly selected as the control group.The baseline data on the gender,age,tumor and ICIs type,history of surgery before medication,history of radiotherapy and chemotherapy,and the related indicators of liver and kidney function,blood lipids,thyroid hormone levels and so on were collected.The relevant indicators of the three groups were statistically analyzed,and the normal thyroid function group and abnormal thyroid function group were compared to evaluate the clinical characteristics and related risk factors of TD caused by ICIs.Results 1.Among 157 patients treated with ICIs,58 cases(36.9%)had thyroid dysfunction,including 39 cases of hypothyroidism(including subclinical hypothyroidism),9 cases of hyperthyroidism(including subclinical hyperthyroidism),and 10 cases of pure related antibody abnormality.2.The analysis of the data of the normal thyroid function group,the abnormal thyroid function group and the control group showed that the age,thyroid stimulating hormone(TSH),and thyroid function of the three groups were significantly different.TSH)baseline level,free triiodothyronine(FT3)baseline level and aspartate transaminase(AST)baseline level were statistically different(P<0.05).There were significant differences in TSH baseline and radiotherapy history between the normal thyroid function group and the abnormal thyroid function group(P<0.05);Multivariate analysis showed that the radiotherapy history(OR=7.291,95% CI= 1.579-33.663,P<.05),baseline TSH level(OR=3.917,95% CI= 1.697-9.038,P<0.05)were the independent risk factors for thyroid dysfunction in cancer patients after ICIs treatment.Conclusion Hypothyroidism is the most common type of TD caused by ICIs in cancer patients.The baseline TSH level and the history of radiotherapy are the independent risk factors for thyroid dysfunction.
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Objective To analyze the frailty of patients with long-term maintenance dialysis(MD)and its influencing factors,and to explore the correlation of different dialysis modalities with the re-infection of novel coronavirus infection(COVID-19)and frailty syndrome.Methods Patients with regular dialysis in Nephrology Department of the Second Affiliated Hospital of Kunming Medical University from February to June 2023 were selected.A cross-sectional survey was conducted to collect clinical data of the patients,including dialysis modality(i.e.maintenance hemodialysis,abbreviated as hemodialysis,and continuous ambulatory peritoneal dialysis,abbreviated as peritoneal dialysis),and whether with re-infection of COVID-19.Patients were divided into 3 groups using Fried's frailty phenotype(FP):non-frailty group,pre-or-intermediate frailty group,and frailty syndrome group.The clinical characteristics of the FP were compared among the three groups.The correlation of frailty with clinical data,dialysis modality,re-infection of COVID-19 in each group was compared.Multifactorial logistic regression was used to analyze the factors influencing the development of frailty syndrome in patients.Results A total of 246 dialysis patients were included in this study,with 77(31.3%)in the non-frailty group,83(33.7%)in the pre-frailty group and 86(35.0%)in the frailty syndrome group.The frailty syndrome group showed characteristics of advanced age,high pre-dialysis creatinine level,low serum albumin level and combined pleural effusion(all P＜0.05).There was no statistically significant difference in the comparison of frailty between the hemodialysis and peritoneal dialysis group(P = 0.960).COVID-19 re-positive patients had higher frailty score than non-re-positive patients.Multifactor logistic regression showed that age,COVID-19 re-infection of COVID-19,serum albumin,pre-dialysis creatinine,and pleural effusion were factors influencing the development of frailty syndrome in dialysis patients(P＜0.05).Conclusion There is high incidence of frailty syndrome in dialysis patients,and there is no correlation of frailty with dialysis modality.High serum albumin level is a protective factor for the development of frailty syndrome in patients,whereas re-infection of COVID-19,advanced age,high pre-dialysis blood creatinine level and pleural effusion are risk factors for the development of frailty syndrome.
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Objective To determine the time point when porcine pancreatic elastase(PPE)induced abdominal aortic aneurysm(AAA)reaches the regression phase in mice and observe the histological characteristics of AAA in regression phase.Methods AAAs were induced by transient intraluminal infusion of PPE in C57BL/6J mice.The diameters of the mouse abdominal aortas were measured before PPE infusion and sacrifice time,day 14 for AAA progression phase or day 56 for regression phase after PPE infusion,respectively.The histological characteristics of the aneurysm lesion site on day 14 and day 56 after surgery were compared and analyzed.Results The diameters of the abdominal aortas were significantly increased in both day 14 and day 56 after PPE infusion groups(diameter growth rate 147％and 155％,respectively)as compared to the baseline diameters.In the day 14 group,the infused aortas showed typical AAA characteristics,such as elastin break/degradation,medial smooth muscle cells depletion,and inflammatory cell diffused infiltration.In the day 56 group after PPE infusion,although the artery diameter did not change significantly as compared to the day 14 group,histology showed that elastin was partially repaired,new smooth muscle cells were added to the damaged aorta media,the infiltrated inflammatory cells were significantly subsided,and the adventitia neovascularization was reduced,showing a significant feature of the disease regression phase.Conclusion In the PPE-induced mouse AAA model,day 56 after surgery is an appropriate time point for observing aneurysm regression,and the histological characteristics of the regression are obvious.
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Objective To study the effect of geniposide(Gen)on the proliferation,migration and angiogenesis of human retinal vascular endothelial cells(hRVECs)induced by high glucose and explore its mechanism.Methods The hRVECs were intervened with different concentrations(0,1,5,10,20,40 and 80 mg·L-1)of Gen for 24 h,and Cell Counting Kit-8(CCK-8)was used to detect the effect of Gen on the proliferation activity of hRVECs.The hRVECs were di-vided into the control group,high glucose(25 mmol·L-1)group,low,middle and high Gen concentration(5,10 and 20 mg·L-1)groups,bevacizumab(BEV,250 μg·L-1)group and high Gen concentration+BEV(250 pg·L-1)group.Cell proliferation activity was detected by CCK-8.The cell migration ability was detected by scratch test.The tube formation ability of cells was detected by the in vitro tube formation assay.The protein expression levels of vascular endothelial growth factor-A(VEGF-A),soluble VEGF receptor-1(sFlt-1),matrix metalloproteinase 2(MMP-2)and matrix metallo-proteinase 9(MMP-9)in cells were detected by Western blot.Results Compared with 0 mg·L-1 Gen,there was no sta-tistically significant difference in the effect of Gen with concentrations of 1,5,10,20,40 and 80 mg·L-1 on the prolifera-tion activity of hRVECs(all P＞0.05).Compared with the control group,the proliferation activity and migration ability of hRVECs in the high glucose group were significantly enhanced(both P＜0.05),the cell circular structure increased,the protein expression levels of VEGF-A,MMP-2 and MMP-9 significantly increased(all P＜0.05),and the protein expression level of sFlt-1 significantly decreased(P＜0.05).Compared with the high glucose group,the proliferative activity and mi-gration ability of cells in all Gen concentration groups and BEV group significantly decreased(all P＜0.05),the circular structure of cells was reduced,the protein expression levels of VEGF-A,MMP-2 and MMP-9 significantly decreased(all P＜0.05),and the protein expression level of sFlt-1 significantly increased(P＜0.05).Compared with the high Gen concentra-tion group,the high Gen concentration+BEV group showed a significant decrease in cell proliferation activity(P＜0.05),a decrease in cell circular structure,a significant decrease in VEGF-A,MMP-2 and MMP-9 protein expression levels(all P＜0.05),and a significant increase in sFlt-1 protein expression level(P＜0.05).Conclusion Gen can inhibit the high glucose-induced proliferation,migration and angiogenesis of hRVECs,and its mechanism may be related to the regulation of VEGF/sFlt-1 axis balance.
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Objective:To determine the incidence of adrenal incidentalomas(AIs) in patients with diabetes mellitus and the metabolism profiles.Methods:A total of 615 hospitalized patients with diabetes mellitus in the Department of Endocrinology and Metabolism of Peking University People′s Hospital from March 2020 to May 2021 were retrospectively included in this study. AIs were screened by unenhanced chest computed tomography(CT) retrospectively and subsequently confirmed by multiplanar reconstruction. Participants′ physical indicators, metabolic profiles, and adrenal function parameters were collected. Unpaired t test, Mann-Whitney U test, and Chi-Square test were adopted to compare the metabolism profiles between diabetes mellitus patients with or without AIs. Regression models were used to estimate the correlations between AIs and the metabolism profiles such as blood glucose, blood lipids, blood pressure, and the adrenal function parameters.Results:Twenty-seven out of 615 participants were detected with AIs(4.4%). Patients with AIs had higher body mass index, waist circumference, and hip circumference than patients without AIs [(29.4±5.1)kg/m 2vs(26.8±3.8)kg/m 2,P=0.018; (102.3±11.7)cm vs(95.8±10.3)cm, P=0.002; (107.3±10.1)cm vs(101.4±7.6)cm, P=0.008]. The levels of serum uric acid and urinary albumin/creatinine ratio were also significantly increased in patients with AIs [(409.6±118.1)μmol/L vs(357.4±100.6)μmol/L, P=0.009; 21.25(7.49, 180.24)mg/g vs 8.60(4.71, 34.56)mg/g, P=0.010]. Besides, individuals with AIs were also associated with a higher risk of co-existing hypertension( P=0.045). Conclusion:The incidence of AIs in patients with diabetes is 4.4%. The presence of AIs in patients with diabetes may associated with increased risk of obesity and hypertension.
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AIM To prepare the nanosuspensions of naringenin phospholipids complex,and to investigate their in vivo pharmacokinetics.METHODS High-pressure homogenization method was applied to preparing the nanosuspensions of phospholipids complex.With stabilizer type,stabilizer-phospholipids complex consumption ratio,homogeneous pressure and homogeneous frequency as influencing factors,particle size,PDI and Zeta potential as evaluation indices,the formulation was optimized by single factor test.The morphology was observed under transmission electron microscope,after which X-ray powder diffraction analysis was performed,solubility,oil-water partition coefficient,dissociation rate of phospholipids complex and accumulative release rate were determined.Twenty-four rats were randomly assigned into four groups and given intragastric administration of the 0.5%CMC-Na suspensions of naringenin and its phospholipids complex,nanosuspensions and nanosuspensions of phospholipids complex(30 mg/kg),respectively,after which blood collection was made at 0,0.25,0.5,1,1.5,2,3,4,5,6,8,10,12 h,HPLC was adopted in the plasma concentration determination of naringenin,and main pharmacokinetic parameters were calculated.RESULTS The optimal formulation was determined to be 50 mg for naringenin consumption,PVP K30+TPGS(1 ∶ 1)as stabilizer,3 ∶ 1 for stabilizer-phospholipids complex consumption ratio,100 MPa for homogeneous pressure,and 10 times for homogeneous frequency,respectively.The obtained spherical-like or oval nanosuspensions of phospholipids complex demonstrated the average particle size,PDI and Zeta potential of(260.53±25.86)nm,0.160±0.024 and(-31.08±1.37)mV,respectively.Naringenin existed in the nanosuspensions of phospholipids complex in an anamorphous state,along with increased solubility,oil-water partition coefficient and dissociation rate of phospholipids complex,and the accumulative release rate reached more than 90%within 4 h.Compared with raw medicine and nanosuspensions,the nanosuspensions of phospholipids complex displayed shortened tmax(P<0.05)and increased Cmax,AUC0-t,AUC0-∞(P<0.05,P<0.01),the relative bioavailability was enhanced to 4.38 times.CONCLUSION The nanosuspensions of phospholipids can enhance naringenin's solubility and dissolution rate,and promote its in vivo absorption.
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Objective:To explore the impact of different six-character qigong training modes on respiratory muscle function early after a stroke.Methods:Sixty-six stroke survivors in the early stage of recovery were randomly divided into a control group, a modified training group, and an ancient training group, each of 22. In addition to routine rehabilitation training, the control group received conventional respiratory training. The modified training and ancient training groups were trained in modified six-character qigong or ancient six-character qigong, respectively, for two weeks. Before the treatment, after the two weeks and one month later, maximum inspiratory pressure (MIP) and maximum expiratory pressure (MEP), forced expiratory volume in one second, forced vital capacity, peak expiratory flow, maximum mid-expiratory flow, and peak inspiratory flow were measured. Diaphragm mobility during quiet inspiration and maximum inspiration were also quantified.Results:After 2 weeks of treatment and at 1 and 3 months after the end of the treatment, all three groups showed significant improvement in MIP, MEP and the pulmonary ventilation indicators, but the average improvement in the modified training group was significantly greater than in the other two groups. Their average diaphragm mobility was also significantly greater.Conclusion:Modified six-character qigong respiratory training is more effective than its ancient counterpart in improving respiratory muscle function, pulmonary ventilation, and diaphragm mobility early after a stroke, with effects which persist for at least one month.
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OBJECTIVE To study the pharmacokinetics of Esketamine hydrochloride nasal spray in rats and ciliary toxicity to maxillary mucosa of bullfrog. METHODS The plasma concentration of esketamine hydrochloride in rats was determined by LC-MS/ MS after intravenous injection of esketamine hydrochloride solution and nasal administration of esketamine hydrochloride； the pharmacokinetic parameters were calculated by using Phoenix WinNonlin 8.1.0 software. Using the maxillary mucosa of isolated bullfrog as a model， the morphological changes of maxillary mucosa were investigated， and the duration and recovery of ciliary oscillation were recorded after nasal administration of esketamine hydrochloride. RESULTS The peak of blood concentration occurred 2 min after nasal administration of esketamine hydrochloride； cmax was （814.58±418.80） ng/mL， AUC0－∞ was （203.75± 92.76） ng·h/mL， and the absolute bioavailability was 60.68%. After nasal administration of esketamine hydrochloride， it was observed that the cilia of bullfrog were arranged neatly， the edges were clear， the cilia tissue structure was complete and the cilia moved actively. The cilia movement time was （178.17±13.30） min for the first time， and after the cilia moved again， the ciliary movement time measured again was （24.50±9.19）min with a relative movement percentage of 53.56%. CONCLUSIONS Esketamine hydrochloride nasal spray has a rapid onset of action， high bioavailability， and low ciliary toxicity.
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Diabetic foot is one of the common chronic complications， the most common cause of hospitalization， and even the main cause of disability and death among diabetic patients. In the process of disease occurrence， development， and treatment， patients experience complex changes in physical， psychological， and social relationships. Their understanding and practice of the disease is a constant process of construction and change， which contains strategic practices influenced by factors such as disease progression， family relationships， culture and traditions of social， and doctor-patient interactions. Based on the research concepts in the field of medical anthropology， this paper applied field research methods such as survey interviews and participatory observation， and took the rich and varied and personalized narrative of diabetic foot patients as the entry point to understand their unique and detailed disease stories， as well as focused on answering the changes in the views of illness， treatment， family， society， and the body outlook experienced by diabetic foot patients. This paper aimed to provide a new perspective for understanding this group， as well as offer valuable insights for improving their treatment and management， which will help promote the overall health and quality of life with diabetic foot patients.
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Background Coal workers' pneumoconiosis (CWP) is a serious occupational lung disease and one of the prescript occupational diseases in China. Epithelial-mesenchymal transition (EMT) is involved in the diffuse fibrosis of lung tissue of pneumoconiosis patients, and its mechanism may be related to the polarization of macrophages regulated by let-7c. Objective To investigate the effect of let-7c on the regulation of macrophage polarization in EMT in rats induced by coal dust exposure with different content of free SiO2. Methods SD rats were randomly divided into a control group, a 5% SiO2 group, a 30% SiO2 group, and a 99.9% SiO2 group, with 16 rats in each group. The rats in each group were tracheally titrated with 100 μL of 20 mg·mL−1 suspension (5% SiO2, 30% SiO2, and 99.9% SiO2) or normal saline, respectively. Alveolar lavage fluid was collected at the ends of the 1st month and the 3rd month. The relative expression levels of M1 or M2 markers, CD86 or CD206, in alveolar macrophages (AMs) were detected by immunofluorescence. The inflammation and fibrosis of lung tissue were observed by hematoxylin-eosin (HE) staining and Masson staining. The expression levels of transforming growth factor-β1 (TGF-β1), E-cadherin, and vimentin were detected by Western blotting. The expression levels of let-7c and c/EBP-δ genes were detected by real-time fluorescence quantitative PCR. Results The HE and Masson staining results showed that compared with the control group, the degree of pulmonary fibrosis in the 5% SiO2 group, the 30% SiO2 group, and the 99.9% SiO2 group gradually increased with the increase of dust exposure time. Compared with the control group, the expressions of CD86 and CD206 in the 5% SiO2 group, the 30% SiO2 group, and the 99.9% SiO2 group gradually increased at the end of the 1st month (F=330.904, 146.801, P<0.05), and the expression of CD86 in each group decreased gradually at the end of the 3rd month (F=331.781, P<0.05), but the expression of CD206 increased (F=1164.190, P<0.05). At the end of the 1st month, the expressions of TGF-β1 (F=8.847, P<0.05) and vimentin (F=13.275, P<0.05) gradually increased, and the expression of E-cadherin (F=6.253, P<0.05) gradually reduced in the 5% SiO2 group, the 30% SiO2 group, and the 99.9% SiO2 group. At the end of the 3rd month, the expressions of TGF-β1 (F=16.833, P<0.05) and vimentin (F=55.021, P<0.05) increased, and the expression of E-cadherin (F=12.790, P<0.05) gradually decreased in all groups. The PCR results showed that compared with the control group, the expression of let-7c mRNA in the 5% SiO2 group, the 30% SiO2 group, and the 99.9% SiO2 group increased at the ends of the 1st month and the 3rd month (F=11.251, 28.136, P<0.05). The expression of c/EBP-δ mRNA decreased in all groups at the ends of the 1st month and the 3rd month (F=49.204, 177.090, P<0.05). Conclusion In response to dust stimulation, let-7c promotes EMT by modulating macrophage polarization, which is involved in the formation of pulmonary fibrosis and thus influences the progression of CWP .
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Aim To screen and study the expression of long non-coding RNA (IncRNA) in rats with middle cerebral artery occlusion (MCAO) with MCAO treated with Tao Hong Si Wu decoction (THSWD) and determine the possible molecular mechanism of THSWD in treating MCAO rats. Methods Three cerebral hemisphere tissue were obtained from the control group, MCAO group and MCAO + THSWD group. RNA sequencing technology was used to identify IncRNA gene expression in the three groups. THSWD-regulated IncRNA genes were identified, and then a THSWD-regu-lated IncRNA-mRNA network was constructed. MCODE plug-in units were used to identify the modules of IncRNA-mRNA networks. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) were used to analyze the enriched biological functions and signaling pathways. Cis- and trans-regulatory genes for THSWD-regulated IncRNAs were identified. Reverse transcription real-time quantitative pol-ymerase chain reaction (RT-qPCR) was used to verify IncRNAs. Molecular docking was used to identify IncRNA-mRNA network targets and pathway-associated proteins. Results In MCAO rats, THSWD regulated a total of 302 IncRNAs. Bioinformatics analysis suggested that some core IncRNAs might play an important role in the treatment of MCAO rats with THSWD, and we further found that THSWD might also treat MCAO rats through multiple pathways such as IncRNA-mRNA network and network-enriched complement and coagulation cascades. The results of molecular docking showed that the active compounds gallic acid and a-mygdalin of THSWD had a certain binding ability to protein targets. Conclusions THSWD can protect the brain injury of MCAO rats through IncRNA, which may provide new insights for the treatment of ischemic stroke with THSWD.
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Objective To investigate the relationship between nuclear factor(NF)-κB signaling pathway and gender differences in alcoholic liver fibrosis. Methods C57BL/6 N mice at 7-8 weeks of age were randomly divided into: male normal group, male model group, female normal group and female model group of 20 mice each. The normal group was fed with control liquid diet for 8 weeks, and the model group was fed with alcoholic liquid diet for 8 weeks combined with 31.5% ethanol gavage (5g/kg twice a week) to establish an alcoholic liver fibrosis model. The mice were executed at the end of 8 weekends, and the alanine aminotransferase (ALT), aspartate aminotransferase (AST) activity, estradiol (E
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Six compounds were isolated from the roots of Ephedra sinica Stapf using various chromatographic techniques such as silica gel column chromatography, thin layer chromatography and semi-preparative HPLC. Their chemical structures were identified by analysis of physicochemical properties and spectral data, and determined as (Z)-docosanylferulate (1), (E)-docosanylferulate (2), bis (2-ethylheptyl) phythalate (3), 2,2′-oxybis (1,4-di-tert-butylbenzene) (4), diisobutyl phthalate (5), bis (2-ethylhexyl) phthalate (6). Among them, compound 1 is a new compound, compounds 2-4 were first isolated from Ephedra. A corticosterone-induced PC-12 cell injury model was used for compound activity screening. The results showed that compounds 1 and 5 significantly improved corticosterone-induced PC-12 cell injury and significantly increased 5-HT7 receptor protein expression in the cells, indicating potential antidepressant activity.
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This study investigated the effect of different carrier materials on the in vitro properties of progesterone solid dispersions. The solid dispersions of the insoluble drug progesterone were prepared by hot melt extrusion technique using rheological properties as the index of investigation, and the in vitro properties of the solid dispersions were characterized. Scanning electron microscope revealed solid dispersions with rough surfaces and agglomerated microstructures into irregular lumpy particles. Differential scanning calorimetry and powder X-ray diffraction showed the change of progesterone crystalline form in solid dispersions from crystalline to amorphous state. In vitro dissolution studies showed that solid dispersions prepared with different carrier materials can effectively improve the dissolution rate of drugs. The results of the study showed that the type of carrier material had a significant effect on the in vitro properties of solid dispersions, providing a reference for the study of solid dispersions in the controlled release of insoluble drugs.
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Needle-free injection technology (NFIT) refers to the drug delivery systems in which drugs are propelled as high-speed jet streams using any of the pressure source to penetrate the skin to the required depth. NFIT is a promising drug delivery system as it enables the injection of liquids, powders, and depot/projectiles, and has the advantages of preventing needle stick accidents, improving drug bioavailability, eliminating needle-phobia, increasing vaccine immunity, simplifying operations and is convenient for patients to use. NFIT and its research background, the structure and classification of needle-free jet injectors (NFJI), drugs that can be delivered using NFJI and the factors affecting the injection effect are comprehensively reviewed in this paper. The limitations and potential development directions are summarized to provide a theoretical basis for the application and development of NFIT.
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AIM: To investigate the effect of unilateral endoscopic dacryocystorhinostomy on binocular surface indexes.METHODS: Totally 45 cases with monocular primary acquired nasolacrimal duct obstruction(PANDO)who successfully underwent endoscopic dacryocystorhinostomy between 1 December 2022 and 31 July 2023 were enrolled in the study. Ocular surface indexes, including the non-invasive tear break-up time(NIBUT), Sj&#xF6;gren's International Collaborative Clinical Alliance ocular staining score(SICCA OSS), Korb score of lid wiper and Schirmer test scores, were collected preoperatively and at 0.5, 1 and 3 mo post-operatively. Subsequently, various indexes were compared at each time point between the operated and healthy eyes pre- and post-operatively.RESULTS: There was no significant differences between operated and healthy eyes in NIBUT, SICCA OSS, Korb scores and Schirmer test(all P>0.05). Furthermore, the Korb scores of operated eye at 0.5, 1 and 3 mo post-operatively were significantly lower than the preoperative value(P=0.034, 0.044, 0.027). Moreover, the Schirmer test score of the operated eye at 1 mo post-operatively was significantly lower than the preoperative value(P=0.0461).CONCLUSION:After a successful endoscopic dacryocystorhinostomy, tear drainage is restored, however, ocular surface damage worsens. These changes typically peak at 1 mo post-operatively before gradually improving.
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Objective A model for studying oral ulcers induced by betel nut-extract was constructed in rats.Changes in the structure and diversity of oral flora were observed to explore the involvement of oral flora and local inflammatory factors in the pathogenesis of oral ulcers induced by betel nut-extract and to provide theoretical support for the prevention and treatment of oral ulcers in the clinic.Methods Thirty SD rats were randomly divided into normal,model and intervention groups(Guilin watermelon cream,8 mg/d for 7 days),with 10 rats/group.The oral mucosa of rats was subcutaneously injected with 10 g/mL of betel nut-extract to generate an oral ulcer model.The histomorphological changes were observed,and ulcer area and ulcer scores were assessed.Local oral tissue tumor necrosis factor-α(TNF-α),interleukin(IL)-2 and IL-8 levels were determined.Oral mucosal tissues were sampled for HE staining and analyzed for the structural distribution of oral flora and the diversity of microbial communities using high-throughput sequencing method.Results Compared with rats in the normal group,those in the model group had an increased ulcer area,significantly increased ulcer scores(P＜0.01),and significantly increased levels of TNF-α,IL-2 and IL-8 in the oral mucosal tissues(P＜0.01).The amount Streptococcus(P＜0.05)and Veillonella(P＜0.001)in the oral saliva of the model group rats was significantly reduced.The model group rats showed oral mucosal epithelial cell hyperplasia or focal necrosis,mucosal lamina propria edema,and hemorrhage accompanied by mass neutrophil and monocyte infiltration.Compared with the model group rats,the intervention group rats had significantly reduced ulcerated area(P＜0.05,P＜0.01)and ulcer scores(P＜0.05).And oral mucosal tissue levels of TNF-α(P＜0.01),IL-2(P＜0.05)and IL-8(P＜0.05),as well as significantly increased Streptococcus(P＜0.001)and Veillonella(P＜0.01)and significantly reduced Staphylococcus(P＜0.01)in the oral saliva.The degree of lesions in the oral mucosal tissues was significantly improved in the intervention group.Conclusions Betel nut-extract can be used to successfully reproduce a rat model of oral ulcer,and it is speculated that the development of oral ulcers after exposure to betel nut-extract may be related to an imbalance in the oral flora and local tissue inflammatory mediators.
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OBJECTIVE To study the protective effect of saikosaponin b2(SSb2)on corticosterone(CORT)induced PC12 cell injury and its mechanism.METHODS ① PC12 cells were divided into the cell control group(24 h of culture with RPMI-1640 medium),CORT group(24 h of culture with CORT 100-800 μmol·L-1)and SSb2 group(24 h of culture with SSb2 1.5625,3.125,6.25,12.5,25,50 and 100 μmol·L-1).MTT assay was used to detect the cell survival rate.②PC12 cells were divided into the cell control group(24 h of culture with RPMI 1640 medium),model group(24 h of culture with CORT 400 μmol·L-1),and model+SSb2 group(3 h pretreatment with SSb2 1.5625,3.125,6.25,12.5 and 25 μmol·L-1,removal of the supernatant before cells were co-incubated with CORT 400 μmol·L-1 and corresponding concentrations of SSb2 for 24 h).MTT assay was used to detect the cell survival rate while micro-plate assay was used to detect the lactate dehydrogenase(LDH)leakage rate of PC12 cells.③PC12 cells were divided into the cell control group,model group and model+SSb2 12.5 μmol·L-1 group.AnnexinV-FITC/PI flow cytometry assay was used to detect PC12 cell apoptosis,ultra-perfor-mance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS)cell metabonomics was used to detect metabolic profile changes and colorimetric assay was employed to detect the glutamic acid content and glutaminase activity in PC12 cells.RESULTS Compared with the cell control group,the cell viability decreased to(55±6)%(P<0.01)when the concentration of CORT was 400 μmol·L-1.When the concentration of SSb2 was higher than 50 μmol·L-1,there was significant toxicity to PC12 cells(P<0.01).②Compared with the cell control group,the cell survival rate was signif-icantly decreased(P<0.01),while the release rate of LDH was significantly increased(P<0.01)in the model group.Compared with the model group,the cell survival rate significantly increased(P<0.05,P<0.01),while the LDH release rate significantly decreased(P<0.01)in the model+SSb2 group.③ Com-pared with the cell control group,cell apoptosis was significantly increased in the model group(P<0.05).Compared with the model group,cell apoptosis was significantly decreased(P<0.05)in the model+ SSb2 group.Metabolomics results show that SSb2 significantly back-regulated nine differential metabo-lites of glutamate,creatine,N-acetylaspartate,L-tyrosine,citric acid,L-isoleucine,lactic acid,glutamine and choline.Further network analysis of the key metabolites regulated by SSb2 yielded five major metabolic pathways:D-glutamine and D-glutamate metabolism,phenylalanine,tyrosine and tryptophan biosynthesis,alanine,aspartate and glutamate metabolism,tyrosine metabolism and arginine biosynthesis.Compared with the cell control group,the content of glutamate and activity of glutaminase were significantly decreased in the model group(P<0.01).Compared with the model group,the content of glutamate(P<0.01)and activity of glutaminase(P<0.05)were significantly increased in the model+SSb2 group.CONCLUSION SSb2 has a neuroprotective effect on CORT-injured PC12 cells,and the mechanism of which is related to inhibition of apoptosis and regulation of metabolic disorders.