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Objective:To investigate the efficacy of pulp revascularization in the treatment of pulp necrosis with periapical periodontitis in young permanent teeth and its effect on the levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in gingival crevicular fluid.Methods:From January 2021 to August 2021, 72 young patients with permanent teeth exhibiting pulp necrosis and apical periodontitis who were treated at Haiyang People's Hospital were included in this study. These patients were subsequently divided into a study group ( n = 35) and a control group ( n = 37), depending on their respective treatment methods. The control group underwent conventional apical angioplasty, whereas the study group underwent pulp revascularization. A comparative analysis was conducted to assess the clinical efficacy of both treatments. Additionally, levels of VEGF and bFGF in gingival crevicular fluid were measured before and after surgery, and these values were compared between the two groups. Relevant clinical indicators and the incidence of adverse reactions were also compared between the study and control groups. Results:The overall response rate in the study group was 94.3% (33/35), which was significantly higher than 70.3% (26/37) in the control group ( χ2 = 7.01, P < 0.05). Prior to surgery, there were no notable differences in VEGF level, bFGF level, root length, or root canal thickness between the two groups (all P > 0.05). However, after surgery, VEGF level, bFGF level, root length, and root canal thickness in the study group were (43.25 ± 4.87) ng/L, (40.72 ± 4.83) ng/L, (8.95 ± 0.27) mm, and (3.08 ± 0.24) mm, respectively. These values were (39.90 ± 4.80) ng/L, (36.05 ± 4.66) ng/L, (8.55 ± 0.18) mm, and (2.90 ± 0.20) mm, respectively, in the control group. There were significant differences in VEGF level, bFGF level, root length, and root canal thickness between the two groups ( t = 2.96, 4.18, 5.67, 2.88, all P < 0.05). After surgery, the scores for apical inflammation, root development, and Visual Analogue Scale (VAS) in the study group were significantly higher than those in the control group ( t = 7.61, 4.83, 9.47, all P < 0.001). The incidence of adverse reactions in the study group was 2.9% (1/35), which was significantly lower than 21.6% (8/37) in the control group ( χ2 = 5.79, P < 0.05). Conclusion:Pulp revascularization exhibits superior curative effects compared with conventional apical angioplasty for the treatment of pulp necrosis and apical periodontitis in young permanent teeth. This treatment effectively alleviates pain, markedly improves tooth function, and has a low incidence of adverse reactions, highlighting its clinical value as a therapeutic option.
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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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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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ObjectiveThis study aimed to identify a potential miRNA-mRNA axis in neurofibromatosis type 2 (NF2)-negative meningiomas, investigate their target relationships, and determine their biological functions. MethodsThe GSE17792 dataset, which contains data related to NF2-negative meningiomas, was downloaded from the Gene Expression Omnibus (GEO) database. The limma package of R software was used to determine the differentially expressed miRNAs (DeMiRNAs). The miRWalk 2.0 database was applied to obtain the target genes of DeMiRNAs. The Search Tool for the Retrieval of Interacting Genes (STRING) database was utilized to build protein-protein interaction (PPI) networks, and hub genes were identified via Cytoscape software. The expression and biological roles of the screened miRNAs were further validated. ResultsAltogether, 86 DeMiRNAs, consisting of 52 upregulated and 34 downregulated miRNAs, were found in NF2-negative meningioma tumor samples compared with arachnoid tissue controls. Fourteen miRNAs associated with 274 target genes were identified among these DeMiRNAs, and miRNA-target gene networks were constructed based on these data. Analysis with cytoHubba showed that two miRNAs (hsa-miR-650 and hsa-miR-623) were among the top 20 key hub genes in the PPI network. Further qRT-PCR experimental verification suggested that the expression of hsa-miR-650 was significantly higher in NF2-negative meningiomas than in normal brain tissues. Downregulation of hsa-miR-650 inhibited the proliferation and induced the apoptosis of NF2-negative meningioma cells. Finally, RAC1 was identified as a target of hsa-miR-650. ConclusionHsa-miR-650 acts as a tumor promoter and might function as a therapeutic target for patients with NF2-negative meningiomas.
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OBJECTIVE To evaluate the palatability and chewability of chewable tablets， and provide reference for the quality evaluation of various types of chewable tablets. METHODS Using self-made Glucosamine hydrochloride chewable tablets as the model drug， the quality test was conducted. The in vitro simulation system for chewable tablets was established by using a texture analyzer and rheometer， and an oral simulation experiment was conducted on chewable tablets. The texture analyzer was used to measure the force required for chewing and simulate the static disintegration process of chewable tablets； the rheometer was adopted to measure the viscoelasticity， thixotropy， and deformability of chewable tablets during the chewing process. RESULTS The disintegration time limit， principal component content， and dissolution of self-made Glucosamine hydrochloride chewable tablets all met the limit requirements. The in vitro simulation results of the texture analyzer showed that self-made chewable tablets were easy to chew in both axial and radial directions， and the force required for chewing was within the range of the chewing force of the teeth； chewable tablets could disintegrate at an appropriate time without being chewed and only taken in the oral cavity. The in vitro simulation results of the rheometer showed that the chewable tablets in the oral cavity exhibited a behavior of elasticity as the main factor and viscosity as the secondary factor through the continuous stirring of the tongue， and the viscosity of the chewable tablets gradually decreased with tongue stirring or tooth chewing； when chewing with teeth， the internal force of the chewing tablets decreased， causing plastic deformation and crushing. After being crushed， the shape couldn’t be restored， making it easy to chew and swallow. CONCLUSIONS The combination of texture analyzer and rheometer can be used to simulate the oral chewing process and evaluate the palatability and chewability of self-made Glucosamine hydrochloride chewable tablets. This model can provide reference for the evaluation of various chewable tablets.
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Aim To investigate the regulatory role and mechanism of resveratrol in inhibiting autophagy and promoting apoptosis in choroidal melanoma cells. Methods Choroidal melanoma cells (MUM2B) were divided into control and experimental groups, and treated with different concentrations of resveratrol (0, 10, 20,40,60,80 μmol ·L
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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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This study aimed to explore the infrared manifestation and role of brown adipose tissue(BAT) in phlegm-dampness me-tabolic syndrome(MS), and to provide objective basis for clinical diagnosis and treatment of phlegm-dampness MS. Subjects were selected from the department of endocrinology and ward in the South District of Guang'anmen Hospital, China Academy of Chinese Medical Sciences from August 2021 to April 2022, including 20 in healthy control group, 40 in non phlegm-dampness MS group and 40 in phlegm-dampness MS group. General information, height and weight of the subjects were collected and body mass index(BMI) was calculated. Waist circumference(WC), systolic blood pressure(SBP) and diastolic blood pressure(DBP) was measured. Triglyceride(TG), high density lipoprotein cholesterol(HDL-C), fasting blood glucose(FBG), fasting insulin(FINS), leptin(LP), adiponectin(ADP) and fibroblast growth factor-21(FGF-21) were detected. The infrared thermal image of the supraclavicular region(SCR) of the subjects before and after cold stimulation test was collected by infrared thermal imager and the changes of infrared thermal image in the three groups were observed. In addition, the differences in the average body surface temperature of SCR among the three groups were compared, and the changes of BAT in SCR were analyzed. The results showed compared with the conditions in healthy control group, the levels of WC, SBP, DBP, TG and FPG in MS groups were increased(P<0.01), and the HDL-C level was decreased(P<0.01). Compared with non phlegm-dampness MS group, phlegm-dampness MS group had higher conversion score of phlegm dampness physique(P<0.01). According to the infrared heat map, there was no difference in the average body surface temperature of SCR among the three groups before cold stimulation. while after cold stimulation, the average body surface temperature of SCR in MS groups was lower than that in healthy control group(P<0.05). After cold stimulation, the maximum temperature of SCR and its arrival time in the three groups were as follows: healthy control group(3 min)>non phlegm-dampness MS group(4 min)>phlegm-dampness MS group(5 min). The thermal deviation of SCR was increased and the average body surface temperature of left and right sides were higher(P<0.01) in healthy control group and non phlegm-dampness MS group, while the thermal deviation of SCR did not change significantly in the phlegm-dampness MS group. Compared with that in healthy control group, the elevated temperature between left and right sides was lower(P<0.01, P<0.05), and compared with that in non phlegm-dampness MS group, the elevated temperature of left side was lower(P<0.05). The changes of the average body surface temperature of SCR in the three groups were in the order of healthy control group>non phlegm-dampness MS group>phlegm-dampness MS group. Compared with the conditions in healthy control group and non phlegm-dampness MS group, FINS, BMI and FGF-21 levels were increased(P<0.01,P<0.05), while ADP level was decreased(P<0.01, P<0.05) in phlegm-dampness MS group. Moreover, the LP level in phlegm-dampness MS group was higher than that in non phlegm-dampness MS group(P<0.01). It was observed in clinical trials that after cold stimulation, the average body surface temperature of SCR in MS patients was lower than that of the healthy people; the thermal deviation of SCR did not change significantly in the phlegm-dampness MS patients, and the difference in their elevated temperature was lower than that in the other two groups. These characteristics provided objective basis for clinical diagnosis and treatment of phlegm-dampness MS. With abnormal BAT related indicators, it was inferred that the content or activity of BAT in SCR of phlegm-dampness MS patients were reduced. There was a high correlation between BAT and phlegm-dampness MS, and thus BAT might become an important potential target for the intervention in phlegm-dampness MS.
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Humans , Metabolic Syndrome , Adipose Tissue, Brown , Mucus , Adiponectin , Body Mass IndexABSTRACT
Objective:To formulate clinical commissioning procedures, items, and testing method for Flexitron afterloader hardware and software and establish relevant quality control procedures in order to meet national standards and clinical requirements.Methods:Clinical commissioning included hardware, treatment planning system (TPS), and end-to-end (ETE) full-process testing. The radioactive source positioning accuracy was measured using a source position check ruler. The accuracy and linearity of dwell time were evaluated using three method: stopwatch timing, ion chamber measurement, and video analysis. The accuracy of source position simulator, connecting tubes, source position check ruler, and other measuring tools was tested using a high-precision ruler. Films were used for calibration of marker lines and applicators. The electrometer and well chamber were used to calibrate the radioactive source activity. The display and reconstruction accuracies of the TPS were evaluated using physical image data. ETE testing was conducted using a custom-made phantom for scanning, planning, and dose measurement.Results:The accuracy testing result of the commissioning items were within acceptable limits. The deviation in source activity measurements was 0.21%, and the ETE point dose measurement deviation was 2.32%, both of which met the clinical requirements. However, there was a 2 mm difference between the nominal and measured values of the magnetic resonance marker line in the accuracy testing items. Therefore, adjustments were required when using marker line for catheter reconstruction based on magnetic resonance images.Conclusions:By summarizing the clinical commissioning experience of the Flexitron afterloader, this study has developed quality control method and baseline levels of result of afterloader and TPS items, which provides a reference for the commissioning before clinical use.
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Brachytherapy (BT) provides the opportunity to deliver highly potent radiation doses to the tumor, while more effectively sparing the surrounding organs at risk (OAR) due to the proximity of radiation sources to the tumor target and rapid fall-off of the source dose profile. As an important part of radiotherapy for cervical cancer, BT plays an irreplaceable role. The BT process is complex and can be divided into a series of steps. Long time waiting for patients in the state of implantation of the applicator may cause changes in the position of the applicator relative to the tumor and the movement of the OAR. In recent years, artificial intelligence (AI) has made great progress in the medical field. Machine learning and neural network have been widely applied in all aspects of BT, such as implantation of the applicator, image acquisition, segmentation of target area and OAR, reconstruction of the applicator, plan optimization, and treatment delivery, etc. In addition, BT significantly reduces the overall time, improves the homogeneity of operation, and enhances the accuracy of treatment. In this article, the application, development prospects, and challenges of AI in the BT of cervical cancer in recent years were reviewed, aiming to provide novel ideas for the application of AI in BT.
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Objective:To explore the efficacy and adverse effects of 177Lu-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid- D-Phe1-Tyr3-Thr8-octreotide (DOTATATE) in patients with neuroendocrine neoplasms (NEN). Methods:From 2019 to June 2021, 36 patients (26 males, 10 females; age (43.5±12.9) years) with metastatic NEN who were treated with 177Lu-DOTATATE in the Affiliated Hospital of Southwest Medical University were retrospectively analyzed. Toxicities were assessed by using the common terminology criteria for adverse events (CTCAE) version 5.0. Disease progression and tumor response were determined according to the response evaluation criteria in solid tumors (RECIST) version 1.1. Prognostic factors for progression-free survival (PFS) and overall survival (OS) were analyzed by Cox proportional-hazards model. Results:Of 36 patients, the median follow-up time was 19.8 months, the median PFS was 24 months, and the median OS was not reached. The WHO grade Ⅲ (hazard ratio ( HR)=3.59, 95% CI: 1.10-11.73, P=0.025; OS: HR=7.85, 95% CI: 1.50-41.10, P=0.004), 18F-FDG positive (PFS: HR=3.05, 95% CI: 1.04-8.93, P=0.033; OS: HR=5.90, 95% CI: 1.04-33.49, P=0.025), and received systemic chemotherapy before peptide receptor radionuclide therapy (PRRT) (PFS: HR=2.79, 95% CI: 1.01-7.73, P=0.039; OS: HR=5.56, 95% CI: 1.01-30.57, P=0.026) were prognostic factors for PFS and OS. Transient side effects included fatigue (27.8%, 10/36), nausea (5.6%, 2/36), and the most common laboratory toxicities were lymphocytopenia (11.1%, 4/36), followed by mild renal toxicity (8.3%, 3/36) and mild liver injury (5.6%, 2/36). Conclusions:PRRT with 177Lu-DOTATATE is an effective and well-tolerated treatment in patients with NEN. PFS and OS are shorter in patients who are WHO grade Ⅲ NEN, 18F-FDG positive, and received systemic chemotherapy before PRRT.
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Objective:To investigate the influence of SARS-CoV-2 infection on patients after emergency cardiovascular surgery.Methods:The clinical data of 43 patients who underwent emergency cardiac surgery and returned to the center for cardiac intensive care for treatment after surgery from December 1, 2022 to January 31, 2023 at Beijing Anzhen Hospital were retrospectively collected, and patients were divided into SARS-CoV-2 group(22 cases) and non-SARS-CoV-2 group(21 cases) according to whether they were infected by SARS-CoV-2. Postoperative laboratory and test results, as well as complication rates and in-hospital mortality were recorded for all patients.Results:Compared with patients in the non-SARS-CoV-2 group, patients in the SARS-CoV-2 group had significantly lower postoperative lymphocyte counts( P<0.05), significantly higher ALT and AST( P<0.05), and significantly higher postoperative new-onset atrial fibrillation, abnormal liver function, and ICU time( P<0.05), and postoperative AST and postoperative LVEF were risk factors for patients with poor prognosis. Conclusion:Emergency cardiovascular surgery in patients with SARS-CoV-2 infection has an increased incidence of postoperative complications, leading to increased ICU hours in patients.
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The end of the COVID-19 infection peak in 2022 prompts a backlog of cardiovascular surgical patients to gradually return to the hospital, resulting in a surge in cardiovascular surgeries. However, against the backdrop of the COVID-19 pandemic, the clinical practice of cardiovascular surgery faces many problems. Therefore, organized by Beijing Anzhen Hospital, experts in cardiovascular surgery and related fields have formulated hospital expert experience on perioperative treatment principles of cardiovascular surgery for patients infected with COVID-19. This article summarizes the clinical decision-making of patients requiring cardiovascular surgery after COVID-19 infection, and advises on the corresponding recommendations according to the existing evidence-based medical evidence as well as the actual clinical practice experience of relevant experts. The main content of the article includes special requirements for cardiovascular surgical treatment indications in patients with COVID-19 infection, selection of surgical timing, special requirements of preoperative, intraoperative and postoperative management, etc., which aims to provide COVID-19-infected patients with guidance on rational decision-making when receiving cardiovascular surgery.
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Objective To analyze the clinical phenotypes and mutation types of children with X-linked Alport syndrome(XLAS)with mutations in COL4A5 gene,and to explore the relationship between children with XLAS and nephrotic syndrome nephritic type.Methods Thirty-two children with COL4A5 gene mutations detected by second-generation sequencing and finally diagnosed with Alport syndrome at Guangzhou Red Cross Hospital affiliated with Jinan University and the First People's Hospital of Guangzhou between April 2016 and April 2023 were included,and their clinicopathological features and gene mutation characteristics were retrospectively analyzed.Results The mean age of onset of disease in children with XLAS was(3.68±2.07)years old,the mean age at diagnosis(6.56±2.95)years old,12 cases(37.5%)started with isolated hematuria,8 cases(25%)started with hematuria and proteinuria,12 cases(37.5%)started with nephrotic syndrome nephritic phenotype,and the positive family history of the children was found in 11 cases(34.4%),ocular lesions were found in 3 cases(9.37%),ear lesions in 6 cases(18.75%),and 7 cases(21.87%)were found to have developed chronic kidney disease(CKD)in the later follow-up.21 children underwent renal tissue puncture biopsy,and electron microscopy showed thinning of the basement membrane(diffuse or segmental)in 13 cases(61.9%),and uneven thickness of the basement membrane in 8 cases(38.09%);light microscopy showed thinning of the basement membrane in 13 cases(61.9%);light microscopy showed thinning of the basement membrane in 8 cases(38.09%);and light microscopy showed thinning of the basement membrane in 3 cases(11.5%).(38.09%);light microscopy:focal segmental glomerulosclerosis(FSGS)in 2 cases(9.52%),mesangial proliferative glomerulonephritis(Ms PGN)in 11 cases(52.38%),and minimal change disease(MCD)in 8 cases(38.09%).The type of mutation was categorized as missense mutation in 12 cases(37.5%),shear site mutation in 9 cases(28.12%),nonsense mutation in 6 cases(18.75%),deletion mutation in 3 cases(9.37%),and code shift mutation in 2 cases(6.25%).Genetic mutations were present in 22 cases(68.75%);spontaneous mutations were present in 10 cases(27.02%).Conclusions Children with XLAS have atypical clinical manifestations and pathologic features in the early stage of the disease,and the progress is slow,and some of them are easy to be misdiagnosed as nephrotic syndrome nephritis type in the early stage,so it is important to improve the genetic test for this disease as early as possible,and to make reason-able drug choices to predict the prognosis scientifically.
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Objective:To investigate the clinical characteristics of patients with multiple myeloma (MM) combined with kidney injury and the risk factors associated with the occurrence of kidney injury.Methods:The clinical data of 96 newly treated MM patients in Heze Municipal Hospital from January 2017 to June 2021 were retrospectively analyzed, and the patients were divided into the kidney injury group (33 cases) and the non-kidney injury group (63 cases) based on whether the blood creatinine was >177 μmol/L at the time of diagnosis. The general data and laboratory results of the two groups were compared. The risk factors for kidney injury in MM patients were analyzed by logistic regression method, and the receiver operating characteristic (ROC) curve was drawn to assess the predictive value of each risk factor for the occurrence of kidney injury in MM patients.Results:Compared with the non-kidney injury group, hemoglobin was lower in the kidney injury group, and white blood cell count, blood uric acid, urea nitrogen, β 2-microglobulin (β 2-MG), cystatin C, the proportion of patients with light chain type, and the proportion of patients with international staging system (ISS) stage Ⅲ were higher in the kidney injury group, and the differences were statistically significant (all P < 0.05). Thirty-four patients underwent fluorescence in situ hybridization (FISH) test, and 22 cases (64.7%) had abnormal results. In the non-kidney injury group, genetic testing were performed in 26 cases, and the results were abnormal in 14 cases, including 11 cases (42.3%) of IgH rearrangement, 4 cases (15.4%) of RB1 deletion, 4 cases (15.4%) of 1q21 amplification, and 1 case (3.8%) of P53 deletion; in the kidney injury group, 8 cases underwent genetic testing, and all results were abnormal, including 6 cases (75.0%) of IgH rearrangement, 5 cases (40.0%) of RB1 deletion, and 2 cases (25.0%) of 1q21 amplification. The rate of RB1 mutation in the kidney injury group was higher than that in the non-kidney injury group, and the difference was statistically significant ( χ2 = 4.43, P = 0.035). Logistic regression analysis showed that elevated blood uric acid ( OR = 1.009, 95% CI 1.002-1.016, P = 0.015) and ISS stage Ⅲ ( OR = 16.401, 95% CI 1.174-229.164, P = 0.038), elevated white blood cell count ( OR = 1.833, 95% CI 1.020-3.294, P = 0.043), elevated β 2-MG ( OR = 1.320, 95% CI 1.009-1.728, P = 0.043), and decreased hemoglobin ( OR = 0.900, 95% CI 0.832-0.922, P = 0.008) were independent risk factors for the development of kidney injury in MM patients. According to the area under the ROC curve (AUC), blood uric acid (AUC = 0.775, 95% CI 0.675-0.875, P < 0.001), white blood cell count (AUC = 0.696, 95% CI 0.583-0.809, P = 0.002), β 2-MG (AUC = 0.822, 95% CI 0.732-0.911, P < 0.001), hemoglobin (AUC = 0.755, 95% CI 0.652-0.857, P < 0.001), and ISS stage Ⅲ (AUC = 0.763, 95% CI 0.669-0.856, P < 0.001) had predictive value for kidney injury in MM. Conclusions:MM patients have a high incidence of combined kidney injury, and active monitoring and control of risk factors may improve the outcome and prognosis of patients.
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Based on the dual needs of analgesia and anti-inflammation in trauma treatment, this study uses acetaminophen and moxifloxacin hydrochloride as active pharmaceutical ingredients and develops a composite bilayer tablet with a dual-phase drug release system by using binder jet 3D printing technology. Due to the complexity of the 3D printing process, there is an interaction between the various parameters. Through the optimization of the process, the relationship between the key process parameters can be determined more intuitively. In this study, the process of extended-release tablets was optimized to maintain the mechanical properties of the tablets while realizing the regulation of release. The full-factor experimental design of three central points 23 was used to analyze the factors that significantly affect the quality attributes of extended-release tablets and the interaction between factors. The optimal extended-release process parameters were obtained by the response optimizer: the inkjet quantity of the printing ink was 10 (about 13.8 pL), the powder thickness was 180 μm, and the running speed was 360 mm·s-1. The in vitro of release of 3D printed composite bilayer tablets showed that the in vitro of release of 3D printed tablets and commercially available tablets conformed to the Ritger-Peppas release model. The results of porosity showed that the immediate-release layer of the preparation has many pores and large pore size, and the dissolution of the immediate release layer within 15 min was greater than 85%. The internal pore size of the extended release layer is large, but it can still release slowly for up to 8 h, the mechanism may be related to the extended release of HPMC gelation. On the basis of verifying the rationality of the design goal of 3D printed composite bilayer tablets, this study also provides a theoretical basis for the preparation of 3D printing complex preparations.
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OBJECTIVE To analyze the efficacy and safety of polymyxin B in the treatment of carbapenem-resistant Klebsiella pneumoniae （CRKP）-bloodstream infection （BSI） in patients with hematologic malignancies. METHODS The medical records of patients with hematologic malignancies with CRKP-BSI who received polymyxin B for at least 3 days in our hospital from September 2019 to June 2021 were retrospectively analyzed. All patients were initially treated with a triple therapy namely polymyxin B+tigecycline+carbapenems for anti-infection therapy. RESULTS A total of 10 patients were enrolled as the study subjects. Eleven strains of CRKP were cultured in blood， including 10 strains of CRKP produced Klebsiella pneumoniae carbapenemase（KPC） and 1 strain of CRKP produced both KPC and metal-beta-lactamase； 9 strains were sensitive to colistin， 7 strains were sensitive to tigecycline， 5 strains were sensitive to amikacin and 2 strains were sensitive to compound sulfamethoxazole. All patients were accompanied by neutropenia， with an average duration of （14.1±6.4） days. They were all characterized by fever， chills and fatigue. After treatment， 6 patients were cured and discharged， 4 patients died of ineffective treatment of septic shock. No serious adverse events related to polymyxin B occurred in all patients. CONCLUSIONS Polymyxin B can be used as a therapeutic drug for CRKP-BSI in patients with hematological malignancies. No serious adverse event related to polymyxin B occurs during the treatment.
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Diabetic peripheral neuropathy (DPN) is one of the most common microvascular complications occurring in both type 1 and type 2 diabetes mellitus patients, which often results in patients suffering from severe hyperalgesia and allodynia. Up to now, the clinical therapeutic effect of DPN is still unsatisfactory. Metformin is an anti-diabetic drug that has been safely and widely used for the treatment of type 2 diabetes for decades. Studies have shown that metformin can improve pain caused by DPN, but its effects on the nerve conduction velocity and morphology of the sciatic nerve of DPN, and the mechanism for improving DPN are not clear. Therefore, the STZ-induced model of type 1 DPN in SD rats was used to study the effects of metformin on DPN, and to preliminarily explore its mechanism in this study. All animal experiments were carried out with approval of the Experimental Animal Welfare Ethics Committee of the Institute of Materia Medica (Chinese Academy of Medical Sciences and Peking Union Medical College). After the model was established successfully, STZ diabetic rats were randomly divided into a model group and a metformin treatment group, and 10 normal SD rats were selected as the normal control group, and the rats were intragastrically administered for 12 weeks. The results showed that metformin significantly reduced blood glucose, glycosylated hemoglobin, food consumption and water consumption in STZ rats. Metformin markedly increased the motor nerve conduction velocity and mechanical stabbing pain threshold, prolonged the hot plate latency threshold, and improved the pathological morphological abnormalities of the sciatic nerve in STZ rats. In addition, metformin increased the content of glutathione (GSH), enhanced the activities of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), and reduced the content of malondialdehyde (MDA) in serum and sciatic nerve of STZ diabetic rats, as well as regulating the expression of genes related to oxidative stress in the sciatic nerve. Metformin obviously reduced the levels of pro-inflammatory factors such as tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 in the serum in STZ rats, and inhibited the gene expression of these inflammatory factors in the sciatic nerve. In summary, metformin significantly increased nerve conduction velocity, improved sciatic nerve morphological abnormalities and pain in DPN rats, which may be related to its effect in improving oxidative stress and reducing inflammation.
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Aim To investigate the role of TGF-β/Smad signaling pathway in rheumatoid arthritis (RA) - associated postinterstitial pulmonary fibrosis in mice. Methods The mouse model of RA was constructed by subcutaneous administration of complete Freund's adjuvant (CFA) and chicken II collagen (Col-II) to the tail root of mice. The blank group was given the same amount of distilled water, and the control group was given the same amount of glacial acetic acid (solvent). The degree of toe swelling (joint swelling degree and arthritis index) was monitored to evaluate the mouse modeling. The pathological changes of mouse lung tissues were observed by HE and Masson staining. The expression of TGF-β in lung tissues were observed by immunohistochemical staining. The level of hydroxyproline in lung tissues was measured by chemiluminescence method. The expressions of Smad2, Smad3 and phosphorylated p-Smad2 and phosphorylated p-Smad3 in lung tissues were detected by Western blot. Results Compared with blank group and solvent group, the joint swelling and arthritis index of model group significantly increased. Twenty-one days after administration, HE staining showed inflammatory changes in lung interstitium of the model group, Masson staining showed collagen fiber deposition and obvious fibrosis in lung interstitium of the model group, and immunohistochemical staining showed that the expression of TGF-β in cytoplasm of lung interstitial cells of the model group increased, which was brown and yellow. Meanwhile, hydroxyproline was significantly raised in lung tissue homogenate of the model group. Further WB analysis showed that compared with blank group and solvent group, the expression of p-Smad2 and pSmad3 in lung tissues of the model group was significantly up-regulated (P < 0. 05, P < 0. 01). Conclusions RA can give rise to pulmonary fibrosis, and the expressions of p-Smad2 and p-Smad3 are up-regulated, which is be pivotal in pulmonary fibrosis and RA-related post-interstitial pulmonary fibrosis.