ABSTRACT
Molecular dynamics simulation technology relies on Newtonian mechanics to simulate the motion of molecular system of the real system by computer simulation. It has been used in the research of self-assembly processes illustration and macroscopic performance prediction of self-assembly nano-drug delivery systems (NDDS) in recent years, which contributes to the facilitation and accurate design of preparations. In this review, the definitions, catalogues, and the modules of molecular dynamics simulation techniques are introduced, and the current status of their applications are summarized in the acquisition and analysis of microscale information, such as particle size, morphology, the formation of microdomains, and molecule distribution of the self-assembly NDDS and the prediction of their macroscale performances, including stability, drug loading capacity, drug release kinetics and transmembrane properties. Moreover, the existing applications of the molecular dynamic simulation technology in the formulation prediction of self-assembled NDDS were also summarized. It is expected that the new strategies will promote the prediction of NDDS formulation and lay a theoretical foundation for an appropriate approach in NDDS studies and a reference for the wider application of molecular dynamics simulation technology in pharmaceutics.
ABSTRACT
Heat-sensitive moxibustion is the appropriate technique of the external treatment in traditional Chinese medicine and it is widely used in community because of its "easy learning, simple operation and clear curative effect". Pragmatic randomized controlled trial is a main intervention design in the real world study, which provides a high-level evidence for the effectiveness assessment of heat-sensitive moxibustion in community management. Focusing on the key links of randomization, e.g. block randomization, stratified randomization, cluster randomization, sample size allocation, allocation concealment and blinding, the paper elaborates the advantages, disadvantages and technical details of two-stage randomization with consideration of patient preference in pragmatic randomized controlled trials of heat-sensitive moxibustion in community. It facilitates improving the quality of evidence, reproducibility and methodological homogeneity among different trials.
Subject(s)
Humans , Hot Temperature , Moxibustion , Patient Preference , Random Allocation , Reproducibility of ResultsABSTRACT
Based on the community research experience of heat-sensitive moxibustion, this study explained technical recommendations for pragmatic randomized controlled trials (pRCTs) of heat-sensitive moxibustion in community from 7 aspects: selection of community research sites, ethical approval and registration, patient recruitment, training of standard operating procedures, ensuring patient compliance, quality control of follow-up visits and patient safety, which aimed to reduce the difficulty of research execution and improve the quality of pRCTs implementation and follow-up visits of heat-sensitive moxibustion.
Subject(s)
Humans , Follow-Up Studies , Hot Temperature , Moxibustion/methods , Randomized Controlled Trials as TopicABSTRACT
Objective To investigate the effects of nitroquine on the development of different stages of Plasmodium yoelii in Anopheles stephensi. Methods An. stephensi mosquitoes were fed with conventional sucrose water or sucrose water containing 100 μmol/L nitroquine one day prior to P. yoelii infection. Following starvation for 24 hours, mosquitoes were fed with the blood of Kunming mice infected with P. yoelii, and the number of oocysts was observed in the stomach of An. stephensi. After 6 days and 14 days of infection, the mosquitoes were starved for 24 hours, and then fed with conventional sucrose water or nitroquine treated sucrose water. The An. stephensi mosquitoes were starved for 24 hours 6 and 14 days post-infection with P. yoelii, and then fed with conventional sucrose water or nitroquine-containing sucrose water, the numbers of P. yoelii sporozoites were examined in the hemolymph and salivary glands of An. stephensi. Results Following exposure to nitroquine-containing sucrose water one day prior to P. yoelii infections, the number of P. yoelii oocysts was significantly lower in the An. stephensi stomach on day 7 (119.2 ± 16.1 vs. 207.3 ± 21.8; t = 3.207, P < 0.05). After conventional sucrose water was ceased for 24 hours on day 6, and An. stephensi was fed with nitroquine-containing sucrose water, the number of P. yoelii sporozoites peaked in the hemolymph on day 14 in the nitroquine treatment group (952.3 ± 22.7) and on day 12 in the sucrose water treatment group (1 287.0 ± 39.0), and there was a significant difference in the number of sporozoites in the salivary glands between the nitroquine treatment group and the sucrose water treatment group (9 467.0 ± 1 304.0 vs. 10 533.0 ± 758.7; t = 0.707, P = 0.506) on day 17. After conventional sucrose water was ceased for 24 hours on day 14, and An. stephensi was fed with nitroquine-containing sucrose water, the number of sporozoites in the salivary glands was significantly greater in the nitroquine treatment group than in the sucrose water treatment group (21 900.0 ± 2 613.0 vs. 10 533.0 ± 732.3; t = 4.188, P < 0.05). Conclusions Nitroquine treatment exhibits diverse effects the development of different stages of P. yoelii, and nitroquine treatment may reduce the transmission of P. yoelii in uninfected An. stephensi.
ABSTRACT
Particle design, based on the concept of "quality by design", combines the elements of microbiology, formulation science, heat and mass transfer, solid state physics, powder science, and nanotechnology. It is widely used to develop particles with excellent functional properties. Without affecting the active ingredients, the modification technology of traditional Chinese medicine (TCM) powder based on particle design theory, could improve the flowability, tabletability, disintegration and dissolution behavior, hygroscopicity, wettability, and other functional properties at the physical structure level. This greatly promotes the development of solid preparations of TCM. The present review aims to summarize and discuss the research progress of powder modification of TCM from the perspective of the theory of particle design, powder modification technology, equipment used for powder modification, application in TCM and modification mechanism mainly based on researches published in recent ten years. This review could provide ideas and theory basis for the development of particle design.
ABSTRACT
OBJECTIVES@#To investigate the efficacy and application value of plasma exchange as an adjuvant therapy in children with hemophagocytic syndrome (HPS).@*METHODS@#A prospective randomized controlled trial was designed. Forty children with severe HPS were enrolled, who were treated in the pediatric intensive care unit (PICU) of Hunan Children's Hospital from October 2018 to October 2020. The children were randomly divided into a plasma exchange group and a conventional treatment group using a random number table, with 20 children in each group. The children in the conventional treatment group received etiological treatment and conventional symptomatic supportive treatment, and those in the plasma exchange group received plasma exchange in addition to the treatment in the conventional treatment group. The two groups were compared in terms of general information, clinical symptoms and signs before and after treatment, main laboratory markers, treatment outcome, and prognosis.@*RESULTS@#Before treatment, there were no significant differences between the two groups in gender, age, course of the disease before admission, etiological composition, pediatric critical illness score, involvement of organ or system functions, and laboratory markers (P>0.05). After 7 days of treatment, both groups had remission and improvement in clinical symptoms and signs. After treatment, the plasma exchange group had significantly lower levels of C-reactive protein, procalcitonin, and serum protein levels than the conventional treatment group (P<0.05). The plasma exchange group also had significantly lower levels of alanine aminotransferase and total bilirubin than the conventional treatment group (P<0.05). The length of stay in the PICU in the plasma exchange group was significantly shorter than that in the conventional treatment group (P<0.05). The plasma exchange group had a significantly higher treatment response rate than the conventional treatment group (P<0.05). There were no significant differences between the two groups in the total length of hospital stay and 3-month mortality rate (P>0.05).@*CONCLUSIONS@#Plasma exchange as an adjuvant therapy is effective for children with severe HPS. It can improve clinical symptoms and signs and some laboratory markers and shorten the length of stay in the PICU, and therefore, it may become an optional adjuvant therapy for children with severe HPS.
Subject(s)
Child , Humans , Intensive Care Units, Pediatric , Lymphohistiocytosis, Hemophagocytic/therapy , Plasma Exchange , Plasmapheresis , Prospective StudiesABSTRACT
A total of 15 batches of the substance reference of Guizhi Jia Gegen Decoction(GZGGD) were prepared and the characteristic fingerprints of them were established. Furthermore, the similarity of the fingerprints and peak attributes were explored. The extraction rate, and the content and the transfer rate ranges of the index components, puerarin, paeoniflorin, liquiritin, and ammonium glycyrrhizate were determined for the analysis of the quality value transfer. The result demonstrated that the fingerprints of the 15 batches of the samples showed high similarity(>0.99). A total of 15 characteristic peaks were identified from the fingerprints, with 10 for Puerariae Lobatae Radix, 1 for Cinnamomi Ramulus, 2 for Paeoniae Radix Alba, and 2 for Glycyrrhizae Radix et Rhizoma. The content of puerarin was 11.05-18.35 mg·g~(-1) and the average transfer rate was 21.27%-39.49%. The corresponding figures were 7.95-10.90 mg·g~(-1) and 23.28%-43.23% for paeoniflorin, 3.25-4.95 mg·g~(-1) and 32.31%-61.27% for ammonium glycyrrhizate, and 3.65-5.80 mg·g~(-1) and 14.57%-27.05% for liquiritin. The extraction rate of the 15 batches of samples was in the range of 16.85%-21.78%. In this paper, the quality value transfer of the substance reference of GZGGD was analyzed based on characteristic fingerprint, content of index components, and the extraction rate. This study is expected to lay a basis for the quality control and further development of GZGGD.
Subject(s)
Ammonium Compounds , Benchmarking , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal , PaeoniaABSTRACT
This study aims to establish a rapid and sensitive UPLC-MS/MS method for simultaneously determining the content of strychnine and paeoniflorin in plasma and brain tissue of rats, and compare the pharmacokinetic behavior and brain tissue distribution of paeoniflorin combined with normal and toxic doses of strychnine in rats after percutaneous administration. Compared with those in the toxic-dose strychnine group, the AUC_(0-t), AUC_(0-∞), and C_(max) of strychnine decreased by 51.51%, 45.68%, and 46.03%, respectively(P<0.01), and the corresponding values of paeoniflorin increased by 91.41%, 102.31%, and 169.32%, respectively(P<0.01), in the compatibility group. Compared with the normal-dose strychnine group, the compatibility group showed insignificantly decreased C_(max), AUC_(0-t), and AUC_(0-∞) of strychnine, increased C_(max) and T_(max) of paeoniflorin(P<0.01), 66.88% increase in AUC_(0-t), and 70.55% increase in AUC_(0-∞) of paeoniflorin. In addition, the brain tissue concentration of strychnine decreased and that of paeoniflorin increased after compatibility. The combination of paeoniflorin with normal dose and toxic dose of strychnine can inhibit the percutaneous absorption of strychnine, and greatly promote the percutaneous penetration of paeoniflorin, whereas the interaction mechanism remains to be explored. The UPLC-MS/MS method established in this study is easy to operate and has good precision. It is suitable for in vivo study of pharmacokinetic behavior and brain tissue distribution of paeoniflorin and strychnine after percutaneous administration in rats, which provides reference for the safe and rational clinical use of strychnine and the combined use of drugs, and lays a solid foundation for the development of external preparations containing Strychni Semen.
Subject(s)
Animals , Rats , Administration, Cutaneous , Brain , Bridged-Ring Compounds/pharmacology , Chromatography, Liquid/methods , Glucosides , Monoterpenes , Rats, Sprague-Dawley , Strychnine , Tandem Mass Spectrometry/methods , Tissue DistributionABSTRACT
UPLC-Q-TOF-MS and serum pharmacochemistry were employed to study the migrating components in rat sera after intragastric administration of the water extracts of Puerariae Lobatae Radix(PLR) and Puerariae Thomsonii Radix(PTR). After the respective intragastric administration of PLR and PTR extracts, blood samples were collected from the orbital vein. The serum samples were treated by protein precipitation method with methanol and acetonitrile at a ratio of 1∶1 and then passed through Agilent ZORBAX RRHD SB-C_(18) column(3 mm×100 mm, 1.8 μm) and Agilent SB-C_(18) pre-column(3 mm×5 mm, 1.8 μm) with 0.1% formic acid aqueous solution(A)-acetonitrile(B) as the mobile phase. The elution was performed at the flow rate of 0.25 mL·min~(-1), the column temperature of 40 ℃, and the injection volume of 2 μL. By comparison of the total ion chromatogram and secondary fragment ion information of PLR and PTR water extracts, PLR-and PTR-containing sera, and blank serum, we found 42 migrating components(including 17 prototype components and 25 metabolites) in the sera of rats treated with PLR and 35 migrating components(including 15 prototype components and 20 metabolites) in the sera of rats treated with PTR. Thirty-three common components were shared by the two treatments, including 13 prototype components and 20 metabolites. The differences of migrating components in the PLR-and PTR-treated rat sera provide a scientific basis for further study of the active components and quality markers of PLR and PTR.
Subject(s)
Animals , Rats , Drugs, Chinese Herbal , Plant Roots , Pueraria , SerumABSTRACT
Due to the characteristics of confusing varieties of Chinese medicinal materials, different sources, complex chemical composition, non-standard preparation process, and non-standard pharmaceutical equipment, the quality of Chinese medicinal preparations is difficult to be controlled and evaluated effectively under the current quality control mode and method of Chinese medicinal preparation. The present study proposed an engineering quality view of Chinese medicine pharmacy and a strategy to control the quality of Chinese medicinal preparations based on the current situation. The "overall, dialectical, and dynamic" multi-factor engineering quality view, covering original medicinal materials, preparation technologies, pharmaceutical equipment, and Chinese medicinal preparations, ensures the traceable process, measurable procedures, and feedback quality. The quality control mode of Chinese medicinal preparation with controllable sources, standardized preparation technologies, green pharmaceutical equipment, and intelligent manufacturing is built up.
Subject(s)
Commerce , Drugs, Chinese Herbal , Medicine, Chinese Traditional , Pharmacy , Quality ControlABSTRACT
In this experiment, Panax notoginseng saponins chitosan nanoparticles(PNS-NPs) were prepared by self-assembly and their appearance, particle size, encapsulation efficiency, drug loading, polydispersity index(PDI), Zeta potential, and microstructure were characterized. The prepared PNS-NPs were intact in structure, with an average particle size of(209±0.258) nm, encapsulation efficiency of 42.34%±0.28%, a drug loading of 37.63%±0.85%, and a Zeta potential of(39.8±3.122) mV. The intestinal absorption of PNS-NPs in rats was further studied. The established HPLC method of PNS was employed to investigate the effects of pH, perfusion rate, and different drugs(PNS raw materials, Xuesaitong Capsules, and PNS-NPs). The absorption rate constant(K_a) and apparent permeability coefficient(P_(app)) in the duodenum, jejunum, ileum, and colon were calculated and analyzed. As illustrated by the results, the intestinal absorption of PNS-NPs was increased in the perfusion solution at pH 6.8(P<0.05), and perfusion rate had no significant effect on the K_a and P_(app) of PNS-NPs. The intestinal absorption of PNS-NPs was significantly different from that of PNS raw materials and Xuesaitong Capsules(P<0.05), and the intestinal absorption of PNS-NPs was significantly improved.
Subject(s)
Animals , Rats , Chitosan/pharmacology , Intestinal Absorption , Nanoparticles , Panax notoginseng/chemistry , Saponins/pharmacologyABSTRACT
OBJECTIVE@#To investigate the serum microRNA (miRNA) expression and examine the impact of miRNA expression profiles on T helper type 17 (Th17)/regulatory T cells (Treg) imbalance among patients with cystic echinococcosis, so as to provide insights into the illustration of the mechanisms underlying chronic Echinococcus granulosus infections, and long-term pathogenesis.@*METHODS@#Total RNA was extracted from the sera of cystic echinococcosis patients and healthy controls, and subjected to high-throughput sequencing with the Illumina sequencing platform. Known miRNAs were annotated and new miRNAs were predicted using the miRBase database and the miRDeep2 tool, and differentially expressed miRNAs were identified. The target genes of differentially expressed miRNAs were predicted using the software miRanda and TargetScan, and the intersection was selected for Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Among the differentially expressed miRNAs with the 20 highest fold changes, miRNAs that targeted genes relating to key transcription factors RORC and FOXP3 that determine the production of Th17 and Treg cells or their important regulatory pathways (PI3K-Akt and mTOR pathways) were matched.@*RESULTS@#A total of 53 differentially expressed miRNAs were screened in sera of cystic echinococcosis patients and healthy controls, including 47 up-regulated miRNAs and 6 down-regulated miRNAs. GO enrichment analysis showed that these differentially expressed miRNA were involved DNA transcription and translation, cell components, cell morphology, neurodevelopment and metabolic decomposition, and KEGG pathway analysis showed that the differentially expressed miRNA were mainly involved in MAPK, PI3K-Akt and mTOR signaling pathways. Among the differentially expressed miRNAs with the 20 highest fold changes, there were 3 miRNAs that had a potential for target regulation of RORC, and 15 miRNAs that had a potential to target the PI3K-Akt and mTOR signaling pathways.@*CONCLUSIONS@#Significant changes are found in serum miRNA expression profiles among patients with E. granulosus infections, and differentially expressed miRNAs may lead to Th17/Treg imbalance through targeting the key transcription factors of Th17/Treg or PI3K-Akt and mTOR pathways, which facilitates the long-term parasitism of E. granulosus in hosts and causes a chronic disease.
Subject(s)
Humans , Echinococcosis/genetics , Gene Expression Profiling , MicroRNAs/metabolism , Phosphatidylinositol 3-Kinases/genetics , Proto-Oncogene Proteins c-akt/genetics , T-Lymphocytes, Regulatory , TOR Serine-Threonine Kinases/genetics , Th17 Cells , Transcription Factors/geneticsABSTRACT
OBJECTIVE@#To investigate the dynamic changes of macrophage numbers and apoptosis during Schistosoma japonicum infection, and to investigate the possible mechanisms of macrophage apoptosis induced by S. japonicum soluble egg antigen (SEA).@*METHODS@#C57BL/6 mice at ages of 6~8 weeks were randomly divided into 4 groups, including three experimental groups and a normal control group. Each mouse in the experimental groups was infected with (12 ± 1) cercariae of S. japonicum via the abdominal skin, and all mice in an experimental group were sacrificed 3, 5, 8 weeks post-infection, respectively, while mice in the control group were not infected with S. japonicum cercariae and sacrificed on the day of S. japonicum infection in the experimental group. Mouse liver specimens and peritoneal exudation cells were sampled in each group, and the dynamic changes of macrophage numbers and apoptosis were detected. Mouse peritoneal macrophages were isolated, purified and treated with S. japonicum SEA, PBS and ovalbumin (OVA) in vitro, and the macrophage apoptosis was detected using flow cytometry. The mRNA and protein expression of BCL-2 protein family members were determined in macrophages using real-time quantitative PCR (qP-CR) and Western blotting assays, and the activation of caspase 3 was determined using flow cytometry and Western blotting. In addition, macrophages were in vitro treated with S. japonicum SEA in presence of a caspase inhibitor, H2O2 or N-acetyl-L-cysteine, and the apoptosis of macrophages was detected using flow cytometry.@*RESULTS@#The total macrophage numbers continued to increase in mouse liver [(0.873 ± 0.106) × 106, (2.737 ± 0.460) × 106 and (3.107 ± 0.367) × 106 cells, respectively; F = 81.900, P < 0.01] and peritoneal specimens [(5.282 ± 1.136) × 105, (7.500 ± 1.200) × 105 and (12.800 ± 0.800) × 105 cells, respectively; F = 55.720, P < 0.01] 3, 5 and 8 weeks post-infection with S. japonicum, and the numbers of apoptotic macrophages also continued to increase in mouse liver [(0.092 ± 0.018) × 106, (0.186 ± 0.025) × 106 and (0.173 ± 0.0270) × 106 cells; F = 57.780, P < 0.01] and peritoneal specimens [(0.335 ± 0.022) × 105, (0.771 ± 0.099) × 105 and (1.094 ± 0.051) × 105 cells; F = 49.460, P < 0.01] 3, 5 and 8 weeks post-infection with S. japonicum. The apoptotic rate of SEA-treated macrophages [(24.330 ± 0.784)%] was significantly higher than that of PBS-[(18.500 ± 1.077)%] and OVA-treated macrophages [(18.900 ± 1.350)%] (both P values < 0.01). There were no significant differences in the mRNA or protein expression of Bcl-2 [Bcl - 2 mRNA expression: (1.662 ± 0.943) vs. (1.000 ± 0.000), t = 1.215, P > 0.05; BCL protein expression: (0.068 ± 0.004) vs. (0.070 ± 0.005), t = 0.699, P > 0.05], Bax [Bax mRNA expression: (0.711 ± 0.200) vs. (1.000 ± 0.000), t = 2.507, P > 0.05; BAX protein expression: (0.089 ± 0.005) vs. (0.097 ± 0.003), t = 2.232, P > 0.05] and Bak [Bak mRNA expression: (1.255 ± 0.049) vs. (1.00 ± 0.00), t = 0.897, P > 0.05; BAK protein expression: (0.439 ± 0.048) vs. (0.571 ± 0.091), t = 2.231, P > 0.05] between in SEA- and PBS-treated macrophages. S. japonicum SEA induced macrophage apoptosis in the presence of a caspase inhibitor (F = 0.411, P > 0.05); however, SEA failed to induce macrophage apoptosis in the presence of H2O2 or NAC (F = 11.880 and 9.897, both P values < 0.05).@*CONCLUSIONS@#S. japonicum SEA may induce macrophage apoptosis through promoting reactive oxygen species expression during S. japonicum infections in mice.
Subject(s)
Animals , Mice , Apoptosis , Caspases , Hydrogen Peroxide , Macrophages , Mice, Inbred C57BL , RNA, Messenger , Schistosoma japonicum , Schistosomiasis japonica , bcl-2-Associated X ProteinABSTRACT
ObjectiveTo investigate the long-term safety of triptolide ferulic acid ethosome gel in percutaneous administration. MethodWe mixed triptolide with ferulic acid to make liposomes gel in different doses and then administrated the gel to SD rats of both sexes with intact skin and damaged skin for 12 weeks. The daily dosages calculated based on triptolide for the low-， middle-， and high-dose groups were 63.75， 127.50， 255.00 μg·kg-1， respectively. The body weight of each rat was measured weekly. The rats were sacrificed in the last week for the determination of serum biochemical parameters and organ indexes as well as the observation of histopathology. The toxicity was assessed based on the body weight and all the parameters and indexes. ResultAfter long-term administration， the body weight and serum biochemical parameters did not show significant difference between the gel-treated groups and the blank group with intact skin， which indicated that the percutaneous administration of triptolide and ferulic acid ethosomes gel was relatively safe. However， the rats in the high-dose group showed sparse hair and were easy to die in the case of unhairing with chloral hydrate at the late stage of the study. Comprared with the female rats with intact skin in the blank control group， the female rats with damaged skin in the middle-dose group showed decreased heart index （P<0.05）， which indicated certain cardiotoxicity. Moreover， damage appeared in skin and lung， which may be influeneced by dosage， sex， and skin state. ConclusionFerulic acid in combination with triptolide is relatively safe for percutaneous administration， whereas there are some risks of skin and lung damage in the case of long-term administration. Individualized administration scheme should be developed according to liver and kidney function and skin conditons to ensure the safety of clinical medication.
ABSTRACT
Objective: The study aimed to investigate the safety and feasibility of intrathoracic modified overlap method in laparoscopic radical resection of Siewert type II adenocarcinoma of the esophagogastric junction (AEG). Methods: A descriptive case series study was conducted. The clinical data of 27 patients with Siewert type II AEG who underwent transthoracic single-port assisted laparoscopic total gastrectomy and intrathoracic modified overlap esophagojejunostomy in Guangdong Provincial Hospital of Chinese Medicine from May 2017 to December 2020 were retrospectively analyzed. The intrathoracic modified overlap esophagojejunostomy was performed as follows: (1) The Roux-en-Y loop was made; (2) The jejunum side was prepared extraperitoneal for overlap anastomosis; (3) The esophagus side was prepared intraperitoneal for overlap anastomosis; (4) The overlap esophagojejunostomy was performed; (5) The common outlet was closed after confirmation of anastomosis integrity without bleeding; (6) A thoracic drainage tube was inserted into the thoracic hole with the diaphragm incision closed. The intraoperative and postoperative results were reviewed. Results: All 27 patients were successfully operated, without mortality or conversion to laparotomy. The operative time, digestive tract reconstruction time and esophageal-jejunal anastomosis time were (327.5±102.0) minute, 50 (28-62) minute and (29.0±7.4) minute, respectively. The blood loss was 100 (20-150) ml. The postoperative time to flatus and postoperative hospital stay were (4.7±3.7) days and 9(6-73) days, respectively. Three patients (11.1%) developed postoperative grade III complications according to the Clavien-Dindo classification, including 1 case of anastomotic fistula with empyema, 1 case of pleural effusion and 1 case of pancreatic fistula, all of whom were cured by puncture drainage and anti-infective therapy. Conclusions: The intrathoracic modified overlap esophagojejunostomy is safe and feasible in laparoscopic radical resection of Siewert type II AEG.
Subject(s)
Humans , Adenocarcinoma/surgery , Anastomosis, Surgical , Esophagogastric Junction/surgery , Feasibility Studies , Gastrectomy/methods , Laparoscopy/methods , Retrospective Studies , Stomach Neoplasms/pathologyABSTRACT
Objective: To investigate the effects of non-muscle myosin Ⅱ (NMⅡ) gene silenced bone marrow-derived mesenchymal stem cells (BMMSCs) on pulmonary extracellular matrix (ECM) and fibrosis in rats with acute lung injury (ALI) induced by endotoxin/lipopolysaccharide (LPS). Methods: The experimental research methods were adopted. Cells from femur and tibial bone marrow cavity of four one-week-old male Sprague-Dawley rats were identified as BMMSCs by flow cytometry, and the third passage of BMMSCs were used in the following experiments. The cells were divided into NMⅡ silenced group transfected with pHBLV-U6-ZsGreen-Puro plasmid containing small interference RNA sequence of NMⅡ gene, vector group transfected with empty plasmid, and blank control group without any treatment, and the protein expression of NMⅡ at 72 h after intervention was detected by Western blotting (n=3). The morphology of cells was observed by an inverted phase contrast microscope and cells labeled with chloromethylbenzoine (CM-DiⅠ) in vitro were observed by an inverted fluorescence microscope. Twenty 4-week-old male Sprague-Dawley rats were divided into blank control group, ALI alone group, ALI+BMMSC group, and ALI+NMⅡ silenced BMMSC group according to the random number table, with 5 rats in each group. Rats in blank control group were not treated, and rats in the other 3 groups were given LPS to induce ALI. Immediately after modeling, rats in ALI alone group were injected with 1 mL normal saline via tail vein, rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group were injected with 1×107/mL BMMSCs and NMⅡ gene silenced BMMSCs of 1 mL labelled with CM-DiⅠ via tail vein, and rats in blank control group were injected with 1 mL normal saline via tail vein at the same time point, respectively. At 24 h after intervention, the lung tissue was collected to observe intrapulmonary homing of the BMMSCs by an inverted fluorescence microscope. Lung tissue was collected at 24 h, in 1 week, and in 2 weeks after intervention to observe pulmonary inflammation by hematoxylin eosin staining and to observe pulmonary fibrosis by Masson staining, and the pulmonary fibrosis in 2 weeks after intervention was scored by modified Ashcroft score (n=5). The content of α-smooth muscle actin (α-SMA), matrix metalloproteinase 2 (MMP-2), and MMP-9 was detected by immunohistochemistry in 2 weeks after intervention (n=3), the activity of superoxide dismutase (SOD), malondialdehyde, myeloperoxidase (MPO) was detected by enzyme-linked immunosorbent assay at 24 h after intervention (n=3), and the protein expressions of CD11b and epidermal growth factor like module containing mucin like hormone receptor 1 (EMR1) in 1 week after intervention were detected by immunofluorescence staining (n=3). Data were statistically analyzed with one-way analysis of variance, Bonferroni method, and Kruskal-Wallis H test. Results: At 72 h after intervention, the NMⅡprotein expression of cells in NMⅡ silenced group was significantly lower than those in blank control group and vector group (with P values <0.01). BMMSCs were in long spindle shape and grew in cluster shaped like vortexes, which were labelled with CM-DiⅠ successfully in vitro. At 24 h after intervention, cell homing in lung of rats in ALI+NMⅡ silenced BMMSC group was more pronounced than that in ALI+BMMSC group, while no CM-DiⅠ-labelled BMMSCs were observed in lung of rats in blank control group and ALI alone group. There was no obvious inflammatory cell infiltration in lung tissue of rats in blank control group at all time points, while inflammatory cell infiltration in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group was significantly less than that in ALI alone group at 24 h after intervention, and alveolar wall turned to be thinner and a small amount of congestion in local lung tissue appeared in rats of the two groups in 1 week and 2 weeks after intervention. In 1 week and 2 weeks after intervention, collagen fiber deposition in lung tissue of rats in ALI alone group, ALI+BMMSC group, and ALI+NMⅡ silenced BMMSC group was significantly aggravated compared with that in blank control group, while collagen fiber deposition in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group was significantly improved compared with that in ALI alone group. In 2 weeks after intervention, modified Ashcroft scores for pulmonary fibrosis of rats in ALI alone group, ALI+BMMSC group, and ALI+NMⅡ silenced BMMSC group were 2.36±0.22, 1.62±0.16, 1.06±0.26, respectively, significantly higher than 0.30±0.21 in blank control group (P<0.01). Modified Ashcroft scores for pulmonary fibrosis of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group were significantly lower than that in ALI alone group (P<0.01), and modified Ashcroft score for pulmonary fibrosis of rats in ALI+NMⅡ silenced BMMSC group was significantly lower than that in ALI+BMMSC group (P<0.01). In 2 weeks after intervention, the content of α-SMA in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group were significantly decreased compared with that in ALI alone group (P<0.05 or P<0.01). The content of MMP-2 in lung tissue of rats in the 4 groups was similar (P>0.05). The content of MMP-9 in lung tissue of rats in ALI alone group was significantly increased compared with that in blank control group (P<0.01), and the content of MMP-9 in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group was significantly decreased compared with that in ALI alone group (P<0.01). At 24 h after intervention, the activity of malondialdehyde, SOD, and MPO in lung tissue of rats in ALI alone group, ALI+BMMSC group, and ALI+NMⅡ silenced BMMSC group were significantly increased compared with that in blank control group (P<0.01), the activity of malondialdehyde in lung tissue of rats in ALI+NMⅡ silenced BMMSC group and the activity of SOD in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group were significantly increased compared with that in ALI alone group (P<0.05 or P<0.01), and the activity of SOD in lung tissue of rats in ALI+NMⅡ silenced BMMSC group was significantly decreased compared with that in ALI+BMMSC group (P<0.01). The activity of MPO in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group was significantly decreased compared with that in ALI alone group (P<0.01), and the activity of MPO in lung tissue of rats in ALI+NMⅡ silenced BMMSC group was significantly decreased compared with that in ALI+BMMSC group (P<0.01). In 1 week after intervention, the protein expression of CD11b in lung tissue of rats in ALI+NMⅡ silenced BMMSC group was significantly increased compared with those in the other three groups (P<0.05 or P<0.01), while the protein expressions of EMR1 in lung tissue of rats in the four groups were similar (P>0.05). Conclusions: Transplantation of NMⅡ gene silenced BMMSCs can significantly improve the activity of ECM components in the lung tissue in LPS-induced ALI rats, remodel its integrity, and enhance its antioxidant capacity, and alleviate lung injury and pulmonary fibrosis.
Subject(s)
Animals , Male , Rats , Acute Lung Injury/therapy , Bone Marrow , Collagen/metabolism , Endotoxins , Extracellular Matrix , Lipopolysaccharides/adverse effects , Lung , Malondialdehyde/metabolism , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Mesenchymal Stem Cells/metabolism , Myosin Type II/metabolism , Pulmonary Fibrosis , Rats, Sprague-Dawley , Saline Solution/metabolism , Superoxide Dismutase/metabolismABSTRACT
This article analyzed the medical records of two patients with Vibrio vulnificus primary sepsis who were admitted to the First Affiliated Hospital of Naval Medical University and reviewed the latest literature. On November 6, 2019, a 54-year-old male patient was admitted to the hospital. The patient's lower limbs were red, swollen, and painful with ecchymosis and hemorrhagic bullae after he ate freshwater products. The emergency fasciotomy was performed 3 h after admission, and the multiple organ failure occurred after operation. The patient was given up treatment 24 h after admission. On August 12, 2020, a 73-year-old male patient was admitted to the hospital. He was in shock state on admission and had hemorrhagic bullae on his right lower limb after he ate seafood. At 3 h post admission, he underwent emergency surgical exploration and amputation of right thigh. Six days later, he received negative pressure wound treatment on the stump. On the 13th day post admission, his families forgo the active treatment and he died 15 d after admission. The two cases were both failed to be diagnosed at the first time, and the disease progressed rapidly. Necrotizing fasciitis and multiple organ failure occurred. After the diagnosis was confirmed, timely fasciotomy and high amputation were performed respectively. The microbiological examinations both reported Vibrio vulnificus. Although the 2 cases were not cured successfully, the course of disease and some indexes of patient with early amputation were better than those of patients with fasciotomy. Vibrio vulnificus is widely distributed and frequently detected in fresh water products. The pathogenic pathway is fuzzy and complex, and it is easy to be misdiagnosed. It is necessary to establish the treatment process of Vibrio vulnificus sepsis. Early and aggressive surgical intervention should be carried out as soon as possible, fasciotomy and debridement should be thorough, and the patients with hemorrhagic bullae should be amputated early. Postoperative comprehensive measures are also important for improving the survival rate of patients.
Subject(s)
Aged , Humans , Male , Middle Aged , Fasciitis, Necrotizing/surgery , Multiple Organ Failure , Sepsis/diagnosis , Vibrio Infections/pathology , Vibrio vulnificusABSTRACT
Gangrenous cholecystitis is a kind of acute cholecystitis, whose course of disease progresses rapidly, early diagnosis is difficult and mortality is high, and clinicians are prone to misdiagnosis and missed diagnosis in clinical work.However, gangrenous cholecystitis has been ignored in various guidelines.This paper systematically summarized the pathogenesis, pathological manifestations, epidemiology, clinical diagnosis and treatment of gangrenous cholecystitis, hoping to provide a complete and clear diagnosis and treatment process for clinicians.
Subject(s)
Humans , Cholecystectomy , Cholecystitis/surgery , Cholecystitis, Acute/surgery , Gangrene/surgeryABSTRACT
Objective:To investigate the clinical characteristics, efficacy and prognostic influencing factors of IgD multiple myeloma (MM) in the new immunotherapy era.Methods:The clinical data of 29 patients diagnosed with IgD MM in the Affiliated Hospital of Xuzhou Medical University from March 2014 to February 2021 were retrospectively collected. The clinical characteristics, treatment regimens and efficacy, especially the efficacy of new drugs and immunotherapy for the disease were analyzed. Kaplan-Meier method was used to analyze the overall survival (OS) and progression-free survival (PFS). Multivariate Cox proportional risk model was used for analysis of prognostic influencing factors.Results:The median age of patients was 58 years. There were 20 cases (69.0%) below 65 years, 12 cases (41.4%) of complicated with stomach function damage, 6 cases (20.7%) of extramedullary invasion. All patients were treated with combined therapy containing proteasome inhibitor bortezomib in the first-line therapy, and the overall response rate was 82.8% (24/29). Among 21 relapsed/refractory patients, 12 patients were treated with the second-line or above treatment regimen chimeric antigen receptor T cell (CAR-T) immunotherapy, including 9 cases achieving very good partial remission (VGPR) or above; 5 patients were treated with the new drug daratozumab, including 1 case achieving complete remission (CR). The median OS time of 29 patients was 48 months (95% CI 17-79 months), the median PFS time after the first-line treatment was 9 months (95% CI 3-15 months), and the median PFS time after the second-line treatment was 11 months (95% CI 1-21 months). Multivariate Cox regression results showed that CAR-T therapy is an independent influencing factor of the prognosis of relapsed/ refractory IgD MM patients ( HR = 0.094, 95% CI 0.019-0.473, P = 0.004). Conclusions:IgD MM patients are characterized with lower onset age, more renal function damage and a high incidence of extramedullary invasion. The first-line therapy containing proteasome inhibitor has a better short-term efficacy, and CAR-T therapy can improve the remission rate and survival rate of relapsed/refractory IgD MM to a certain extent.
ABSTRACT
Objective:To evaluate the feasibility and clinical outcomes of navigation-assisted total knee arthroplasty (TKA) using adjusted restricted kinematic alignment (arKA).Methods:Data of 14 consecutive cases of OrthoPilot navigation-assisted TKA using arKA from October 2019 to September 2021 were retrospectively analyzed, including 3 males and 9 females. The average age was 67.71±8.96 years with mean body mass index (BMI) 25.94±3.12 kg/m 2. 27 consecutive patients who underwent navigation-assisted TKA using aMA during the same period were assessed as the control group. There were no significant differences in gender, age or BMI between the two groups. Intraoperative parameters including operative duration, tibia resection angle, frontal femoral angle, axial femoral angle, joint line translation, medial and lateral gap in extension and flexion position were recorded. Radiographic parameters including hip-knee-ankle (HKA) angle, coronal femoral component angle (cFCA), coronal tibial component angle (cTCA), sagittal femoral component angle (sFCA) and sagittal tibial component angle (sTCA) were measured. Functional outcomes were assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Hospital for Special Surgery (HSS) score. Surgery-related complications were recorded. Results:All cases were followed up. The mean follow-up of arKA group was 18.57±6.98 months and follow-up of aMA group was 22.15±4.91 months. The intraoperative tibial resection was 3.07°±1.00° in arKA group versus 0.67°±0.56° in aMA group ( P<0.05). The lateral cutting height of tibia was 9.07±1.82 mm in arKA group versus 6.89±2.94 mm in aMA group ( P<0.05). The lateral gap in flexion was 1.71±0.83 mm in arKA group versus 1.04±0.71 mm in aMA group ( P<0.05). The difference of medial-lateral flexion laxity was 1.14±0.86 mm in arKA group versus 0.41±0.75 mm in aMA group ( P<0.05). The postoperative HKA angle was 174.10°±1.63° in arKA group versus 177.12°±2.07° in aMA group ( P<0.05). The cTCA was 87.58°±0.85° in arKA group versus 89.14°±1.23° in aMA group ( P<0.05). The cFCA was 93.10°±1.75° in arKA group versus 90.41°±3.01° in aMA group ( P<0.05). There was no statistical difference between the two groups in sFCA (1.30°±0.82° vs. 1.56°±1.19°), sTCA (87.16°±0.95° vs. 87.79°±1.04°) and femoral notching (7.1% vs. 11.1%). The preoperative HSS score in arKA group was 46.07±4.68 and HSS score at 1 month postoperatively was 73.86±3.48 ( P<0.05). The preoperative HSS score in aMA group was 47.04±4.52 and HSS score at 1 month postoperatively was 74.04±3.57 ( P<0.05). There was no statistical difference between the two groups in WOMAC score (12.93±2.37 vs. 12.63±2.34) and HSS score (86.86±2.74 vs. 86.11±2.95) at 6 months postoperatively. 2 cases (14.3%) in arKA group and 5 cases (18.5%) in aMA group had deep venous thrombosis (χ 2=0.12, P=0.733). Conclusion:Navigation-assisted TKA using arKA offers the surgeons a new alignment option for severe knee deformity with satisfactory clinical outcomes, the arKA technique has advantages in soft tissue protection and gap balance regulation compared to aMA technique.