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OBJECTIVE To study the effects of leonurine on pancreatic injury in rats with severe acute pancreatitis (SAP), and to explore its mechanism based on the high-mobility group box 1 (HMGB1)/receptor for advanced glycation end products (RAGE) signaling pathway. METHODS SAP rat model was constructed by injecting 5% sodium taurocholate into the bile duct of the pancreas. Model rats were randomly divided into model group, low dose leonurine group (8 mg/kg), high dose leonurine group (16 mg/kg), HMGB1 overexpression group (8 μg/kg), and high dose leonurine+HMGB1 overexpression group (16 mg/kg+8 μg/kg), with 14 rats in each group. Another 14 rats were selected as the sham operation group. Rats in each group were injected with corresponding drugs or normal saline via abdominal cavity or tail vein once a day for 5 consecutive days. After the last administration, the levels of serum amylase (AMS) and lipase (LPS) were detected; the pathological injury of pancreatic tissue was observed; the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), malondialdehyde (MDA) and superoxide dismutase (SOD), mRNA and protein expressions of HMGB1 and RAGE in pancreatic tissues were detected. RESULTS Compared with model group, the structure of pancreatic tissue in rats gradually recovered in low and high dose leonurine groups; inflammatory cell infiltration gradually decreased; the pathological injury score and the levels of AMS, LPS, TNF-α, IL-6, MDA, the mRNA and protein expressions of HMGB1 and RAGE were significantly decreased, while the SOD levels were significantly increased (P<0.05). The high dose leonurine group showed more significant improvement (P<0.05); the pathological damage of pancreatic tissue in the HMGB1 overexpression group worsened, and except for a decrease in SOD levels, all other quantitative indicators increased significantly (P<0.05). Overexpression of HMGB1 could reduce the improvement effect of high dose leonurine on the above indexes in SAP rats (P<0.05). CONCLUSIONS Leonurine may alleviate pancreatic injury, inflammation and oxidative stress in pancreatic tissue of rats with SAP by inhibiting the HMGB1/RAGE signaling pathway.
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【Objective】 To analyze the independent influencing factors of repeated extracorporeal shock wave lithotripsy (ESWL) in the treatment of upper urinary calculi (UUC), based on which a nomogram model was established to predict the efficacy. 【Methods】 Clinical and imaging data of 203 patients receiving repeated ESWL during Jan.2020 and Dec.2022 were collected, including 117 cases in the successful group and 86 cases in the unsuccessful group.The patients’ age and sex, stone volume (SV), surface area (SA), skin-to-site distance (SSD), maximum CT value, mean stone density (MSD), and stone heterogeneity index (SHI) were compared between the two groups.The independent predictors were analyzed with logistic regression and the meaningful variables (P<0.05) were used to establish a nomogram.The efficacy of the model was evaluated using receiver operating characteristic (ROC) curve and decreasing curve analysis (DCA).Internal validation was also performed. 【Results】 Stepwise regression showed that SV, SSD, MSD and SHI were independent influencing factors (P<0.05).The area under the ROC curve (AUC), optimal threshold, sensitivity and specificity were 0.793 (95%CI: 0.674-0.911), 0.619, 77.1% and 74.0%, respectively.The DCA curve was above two extreme curves.Hosmer-Lemeshow test and calibration curve showed that the nomogram had a good fitting degree (χ2=5.526, P=0.489), and the correction C-index was 0.746. 【Conclusion】 SV, SSD, MSD and SHI are independent predictors of the efficacy of repeated ESWL in the treatment of UUC.The nomogram established based on the above indicators has good predictive efficiency and clinical applicability.
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ObjectiveTo investigate the effect of Shouwuwan on the synaptic plasticity of hippocampal neurons in the rat model of D-galactose-induced aging via the mammalian target of rapamycin (mTOR) signaling pathway. MethodA total of 50 male SPF-grade SD rats were randomized into normal group, model group, vitamin E (0.018 g·kg-1) group, and low- and high-dose (1.08,2.16 g·kg-1, respectively) Shouwuwan groups. Except the normal group, the other four groups were treated with D-galactose (120 mg·kg-1) for the modeling of aging. The rats were simultaneously administrated with corresponding agents by gavage. After six weeks of modeling, Morris water maze test was carried out to examine the behavioral changes. The whole brain and hippocampus samples were collected. The expression of postsynaptic density protein-95 (PSD-95) and synaptophysin (SYN) in the hippocampus was detected by immunohistochemistry. Golgi staining was employed to observe the changes in the morphology and function of neurons. Western blot and Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) were respectively employed to determine the mRNA and protein levels of mTOR, phosphorylated (p)-mTOR, p70 ribosome protein S6 kinase (p70S6K), phosphorylated (p)-p70S6K, eukaryotic translation initiation factor 4E-binding protein 2 (4EBP2), and phosphorylated (p)-4EBP2 in the hippocampus. ResultCompared with the normal group, the model group showed slow swimming (P<0.01), extended total swimming distance (P<0.05), prolonged latency (P<0.01), and decreased crossing number (P<0.01). The modeling inhibited the expression of PSD-95 and SYN in the CA1 region of the hippocampus (P<0.01), with the weakest staining effect and the smallest region, decreased the intersections of hippocampal neuron dendrites with concentric circles at the concentric distance of 100, 140, 180, and 200 μm from the cell body (P<0.01), and reduced the length and density of dendritic spine (P<0.01). In addition, the modeling up-regulated the mRNA levels of mTOR and p70S6K and the protein levels of p-mTOR and p-p70S6K (P<0.01) and down-regulated the mRNA level of 4EBP2 and the protein levels of 4EBP2 and p-4EBP2 (P<0.01). Compared with the model group, low- and high-dose Shouwuwan increased the average swimming speed (P<0.01), shortened the latency (P<0.01), increased the crossing number (P<0.01), promoted the expression of PSD-95 and SYN in the hippocampal CA1 region (P<0.01), increased the intersections between hippocampal neuronal dendrites and concentric circles at the concentric distance of 100, 140, 180,200 μm from the cell body (P<0.01), and increased the number, length, and density of dendritic spine (P<0.01). Furthermore, Shouwuwan down-regulated the protein levels of p-mTOR and p-p70S6K (P<0.01), up-regulated the protein levels of 4EBP2 and p-4EBP2 (P<0.05,P<0.01), down-regulated the mRNA levels of mTOR and p70S6K (P<0.01), and up-regulated the mRNA level of 4EBP2 (P<0.01). ConclusionShouwuwan can improve the learning and memory ability of rats exposed to D-galactose, promote the expression of proteins associated with synaptic plasticity, improve the morphology of neurons, repair neural function, reduce neuronal apoptosis, and inhibit mTOR signaling pathway to delay brain aging.
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Gelsemium elegans is a traditional Chinese herb of medicinal importance, with indole terpene alkaloids as its main active components. To study the expression of the most suitable housekeeping reference genes in G. elegans, the root bark, stem segments, leaves and inflorescences of four different parts of G. elegans were used as materials in this study. The expression stability of 10 candidate housekeeping reference genes (18S, GAPDH, Actin, TUA, TUB, SAND, EF-1α, UBC, UBQ, and cdc25) was assessed through real-time fluorescence quantitative PCR, GeNorm, NormFinder, BestKeeper, ΔCT, and RefFinder. The results showed that EF-1α was stably expressed in all four parts of G. elegans and was the most suitable housekeeping gene. Based on the coexpression pattern of genome, full-length transcriptome and metabolome, the key candidate targets of 18 related genes (AS, AnPRT, PRAI, IGPS, TSA, TSB, TDC, GES, G8H, 8-HGO, IS, 7-DLS, 7-DLGT, 7-DLH, LAMT, SLS, STR, and SGD) involved in the Gelsemium alkaloid biosynthesis were obtained. The expression of 18 related enzyme genes were analyzed by qRT-PCR using the housekeeping gene EF-1α as a reference. The results showed that these genes' expression and gelsenicine content trends were correlated and were likely to be involved in the biosynthesis of the Gelsemium alkaloid, gelsenicine.
Subject(s)
Genes, Essential , Gelsemium/genetics , Peptide Elongation Factor 1/genetics , Transcriptome , Gene Expression Profiling/methods , Alkaloids , Real-Time Polymerase Chain Reaction/methods , Reference StandardsABSTRACT
Objective:To study the value of urine-based multi-dimensional bioinformatics evaluation model (utLIFE model) in early diagnosis and postoperative monitoring of upper urinary tract urothelial carcinoma (UTUC).Methods:Morning urine samples of patients clinically diagnosed with UTUC without bladder cancer from Peking University First Hospital from August 2022 to October 2022 were collected. Urine samples were collected before and after surgery, and DNA was extracted for gene sequencing. The utLIFE model previously constructed by our center was used to calculate the score, based on 155 gene mutation sites and copy number variation, and the score ≥60 was defined as utLIFE positive. The sensitivity of utLIFE model in diagnosis of UTUC was analyzed with postoperative pathology as the gold standard. The utLIFE scores before and after operation were also compared.Results:A total of 53 patients were included in this study, all of whom were confirmed as UTUC by postoperative pathology. The median age of patients was 66 (59, 72) years. Twenty-four cases (45.3%) of UTUC tumors were located in the renal pelvis, 26 cases (49.1%) were located in the ureter, and 2 cases (5.7%)involved both ureter and renal pelvis. There were 27 patients (50.9%) at T 1stage and 26 patients (49.1%) at ≥T 2 stage. Preoperative utLIFE score of 53 patients was 79 (70, 84). The sensitivity of preoperative utLIFE diagnosis of UTUC was 96.2% (51/53). utLIFE showed similar high sensitivity in T 1 stage and ≥T 2 stage [100.0% (27/27) vs. 92.3% (24/26), P=0.236], in N 0 and ≥N 1 stage [ 95.0% (38/40) vs. 100.0% (5/5), P=1.000]. In addition, the sensitivity of preoperative utLIFE was higher than that of urine cytology [ 95.2% (20/21) vs. 23.8% (5/21). P<0.001], fluorescence in situ hybridization (FISH) [ 92.6% (25/27) vs. 55.5% (15/27), P=0.004] and ureteroscopy [ 86.7% (13/15) vs. 60.0% (9/15), P=1.000]. A total of 45 patients postoperative utLIFE samples were collected, and the postoperative utLIFE score was significantly lower than that of preoperative [ 36 (18, 61) vs. 79 (70, 84), P<0.001]. Conclusions:utLIFE, as a non-invasive urine DNA bioinformatics assessment model, is significantly superior to cytology and FISH in early detection and has high sensitivity in diagnosis of UTUC, and can reflect perioperative minimal residual disease levels.
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AIM To establish an HPLC method for the simultaneous content determination of monocaffeyltartaric acid,forsythiaside A,chicoric acid,phillyrin,arctiin and harpagoside in Waigan Fenghan Granules.METHODS The analysis of 70%methanol extract of this drug was performed on a 30℃thermostatic Agilent Zorbax SB-C18 column(250 mm×4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1%phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelengths were set at 278,330 nm.RESULTS Six constituents showed good linear relationships within their own ranges(r≥0.999 4),whose average recoveries were 96.80%-102.61%with the RSDs of 0.26%-1.93%.CONCLUSION This simple and accurate method can be used for the quality control of Xiao'er Qingyan Granules.
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Objective:To compare the efficacy and safety of standard treatment with or without adjuvant chemotherapy in patients with highly malignant non-metastatic prostate cancer.Methods:In this prospective non-randomized controlled study, consecutive non-metastatic prostate cancer patients with pathologically proven Gleason score of 9-10 or Gleason score of 5 admitted to Peking University First Hospital were enrolled. Four to six cycles of chemotherapy using docetaxel ± carboplatin regimen were added or not after standard radical therapy. The primary end point was 5-year event-free survival (EFS), and the secondary end points were distant metastasis-free survival (MFS), overall survival (OS), and treatment-related adverse events. The survival curve was drawn by Kaplan-Meier method. The differences between two groups were analyzed by log-rank test.Results:A total of 176 patients were consecutively enrolled from November 2019 to January 2022 of which 138 patients received only standard radical therapy (control group), and 38 patients received adjuvant chemotherapy after standard radical therapy (chemotherapy group). The median follow-up time was 13.4 (2.0-34.0) months. All patients survived. The 30-month EFS rates in the chemotherapy and control groups were 100% and 85.6%, respectively ( P=0.064). There were no events in the chemotherapy group, while there were 12 cases of events in the control group, including 6 cases of biochemical recurrence and 6 cases of imaging progression. The 30-month MFS rates in two groups were 100% and 91.9%, respectively ( P=0.205). After the 1 vs. 2 propensity score matching, the EFS and MFS rates in two groups were 100% vs. 85.7% ( P=0.056), and 100% vs. 92.2% ( P=0.209), respectively. The incidence rates of grade 2 and above urinary toxicity in the chemotherapy and control groups were 2.6% and 7.2% ( P=0.354), respectively. The incidence rates of grade 2 and above rectal toxicity were 5.3% and 5.1% ( P=0.711), respectively. Grade 3 and above chemotherapy-related toxicity in the chemotherapy group were leukopenia (31.6%), thrombocytopenia (2.6%) and alopecia (13.2%). Conclusion:The addition of adjuvant chemotherapy after standard radical therapy tends to improve the overall EFS of patients with highly malignant prostate cancer, and the adverse effects are tolerable, which should be confirmed by long-term follow-up results.
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OBJECTIVES@#To explore the role and potential mechanisms of chitinase-3-like protein 1 (CHI3L1) in coronary artery lesions in a mouse model of Kawasaki disease (KD)-like vasculitis.@*METHODS@#Four-week-old male SPF-grade C57BL/6 mice were randomly divided into a control group and a model group, with 10 mice in each group. The model group mice were intraperitoneally injected with 0.5 mL of lactobacillus casei cell wall extract (LCWE) to establish a mouse model of KD-like vasculitis, while the control group mice were injected with an equal volume of normal saline. The general conditions of the mice were observed on the 3rd, 7th, and 14th day after injection. Changes in coronary artery tissue pathology were observed using hematoxylin-eosin staining. The level of CHI3L1 in mouse serum was measured by enzyme-linked immunosorbent assay. Immunofluorescence staining was used to detect the expression and localization of CHI3L1, von Willebrand factor (vWF), and α-smooth muscle actin (α-SMA) in coronary artery tissue. Western blot analysis was used to detect the expression of CHI3L1, vWF, vascular endothelial cadherin (VE cadherin), Caspase-3, B cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), nuclear factor κB (NF-κB), and phosphorylated NF-κB (p-NF-κB) in coronary artery tissue.@*RESULTS@#The serum level of CHI3L1 in the model group was significantly higher than that in the control group (P<0.05). Compared to the control group, the expression of CHI3L1 in the coronary artery tissue was higher, while the expression of vWF was lower in the model group. The relative expression levels of CHI3L1, Bax, Caspase-3, NF-κB, and p-NF-κB were significantly higher in the model group than in the control group (P<0.05). The relative expression levels of vWF, VE cadherin, and Bcl-2 were lower in the model group than in the control group (P<0.05).@*CONCLUSIONS@#In the LCWE-induced mouse model of KD-like vasculitis, the expression levels of CHI3L1 in serum and coronary arteries increase, and it may play a role in coronary artery lesions through endothelial cell apoptosis mediated by inflammatory reactions.
Subject(s)
Male , Animals , Mice , Mucocutaneous Lymph Node Syndrome/pathology , Coronary Vessels/pathology , NF-kappa B , Caspase 3/metabolism , bcl-2-Associated X Protein/metabolism , Chitinase-3-Like Protein 1 , von Willebrand Factor/metabolism , Mice, Inbred C57BL , CadherinsABSTRACT
OBJECTIVE@#To investigate the effectiveness of arthroscopic autologous iliac bone grafting with double-row elastic fixation in treatment of recurrent anterior shoulder dislocation combined with massive glenoid bone defects.@*METHODS@#Between January 2018 and December 2021, 16 male patients with recurrent anterior shoulder dislocation combined with massive glenoid bone defects were treated with arthroscopic autogenous iliac bone grafting and double-row elastic fixation. The patients were 14-29 years old at the time of the first dislocation, with an average age of 18.4 years. The causes of the first dislocation included falling injury in 5 cases and sports injury in 11 cases. The shoulders dislocated 4-15 times, with an average of 8.3 times. The patients were 17-37 years old at the time of admission, with an average age of 25.1 years. There were 5 left shoulders and 11 right shoulders. The preoperative instability severity index (ISIS) score of the shoulder joint was 5.8±2.1, and the Beighton score was 4.3±2.6. The University of California Los Angeles (UCLA) score, Constant score, American Shoulder and Elbow Surgeons (ASES) score, and Rowe score were used to evaluate shoulder function, and the degree of the glenoid bone defect repair was observed based on CT after operation.@*RESULTS@#All incisions healed by first intention, and no complication such as incision infection or neurovascular injury occurred. The patients were followed up 12 months. At 12 months after operation, UCLA score, Constant score, ASES score, and Rowe score all significantly improved when compared with the scores before operation ( P<0.05). CT imaging showed the degree of glenoid bone defect was significantly smaller at immediate, 6 and 12 months after operation when compared with that before operation ( P<0.05), and the bone blocks healed with the scapula, and bone fusion had occurred at 12 months.@*CONCLUSION@#Arthroscopic autologous iliac bone grafting with double-row elastic fixation is a safe treatment for recurrent anterior shoulder dislocation combined with massive glenoid bone defects, with good short-term effectiveness.
Subject(s)
Humans , Male , Adolescent , Adult , Young Adult , Shoulder Dislocation/surgery , Bone Transplantation/methods , Arthroscopy/methods , Joint Instability/surgery , Shoulder Joint/surgery , Scapula/surgery , RecurrenceABSTRACT
New drug clinical trials have been considered as a positive way for treating cancer by cancer patients and doctors, and the extended dosing is a special way for patients' withdrawal from antitumor clinical trials to obtain investigational new drugs. However, neither the regulations of expanded dosing nor the detail documents for expanded dosing have been officially published in China. At present, expanded dosing of investigational drugs is still at the exploratory stage in various medical institutions, and a complete management system has not been established to meet patients' urgent needs for drug use. Based on the practical experience of extended dosing in Hunan Cancer Hospital, this paper preliminarily explored the application procedures and ethical review requirements of extended dosing for subjects in antitumor clinical trials. It is necessary to clarify the responsibilities of all patients in the procedure and establish a patient-medical institution-sponsor joint application system. In the process of ethical review, it is recommended that all parties fully consider the risks and benefits of extended dosing for patients, and then the ethics committee makes a comprehensive assessment to decide whether to approve extended dosing.
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Humans , China , Physicians , Antineoplastic Agents/therapeutic useABSTRACT
This article analyzed the mechanism of Danggui Sini Decoction(DSD) in improving kidney injury caused by blood stasis syndrome(BSS) in rats. Firstly, 32 female SD rats were randomly divided into the following four groups: a normal group and a BSS group, both receiving an equal amount of distilled water by gavage; a normal+DSD group and a BSS+DSD group, both receiving 5.103 g·kg~(-1) DSD orally for a total of 14 days. Daily cold water bath was given to establish the BSS model, and on the 14th day, BSS rats were subcutaneously injected with 0.8 mg·kg~(-1) adrenaline. Normal rats were subjected to the water bath at 37 ℃ and injected with an equal volume of distilled water. After the experiment, 24-hour urine, serum, and kidney samples were collected for metabolomic analysis, biochemical measurements, and hematoxylin-eosin(HE) staining. The study then employed ~1H-NMR metabolomic technology to reveal the metabolic network regulated by DSD in improving BSS-induced kidney injury and used network pharmacology to preliminarily elucidate the key targets of the effectiveness of DSD. Pathological and biochemical analysis showed that DSD intervention significantly reduced inflammation and abnormal levels of blood creatinine, blood urea nitrogen, and urine protein in the kidneys. Metabolomic analysis indicated that DSD attenuated BSS-induced kidney injury primarily by regulating 10 differential metabolites and three major metabolic pathways(taurine and hypotaurine metabolism, citrate cycle, and acetaldehyde and dicarboxylic acid metabolism). Network pharmacology analysis suggested that the protective effect of DSD against BSS-induced kidney injury might be related to two key genes, ATP citrate lyase(ACLY) and nitric oxide synthase 2(NOS2), and two main metabolic pathways, i.e., arginine biosynthesis, and arginine and proline metabolism. This study, from the perspective of network regulation, provides initial insights and evidence into the mechanism of DSD in improving kidney injury induced by BSS, offering a basis for further investigation into the molecular mechanisms underlying its efficacy.
Subject(s)
Rats , Female , Animals , Rats, Sprague-Dawley , Network Pharmacology , Drugs, Chinese Herbal/chemistry , Metabolomics , Kidney , Arginine , WaterABSTRACT
OBJECTIVES@#Accurate breast lesion surface localization can guarantee accurate biopsy and local treatment. But there is no guideline to regular equipment and methods for the localization of breast lesions. The conventional non-invasive localization method is marker-based localization. The advantages of this method are simple and efficient. The disadvantages are that markers disappear easily under coupling agents; the positioning length of markers cannot last long on skin; and healthcare associated infection due to many patients using the same marker pen is potentially unavoidable. Breast lesion sticker (called sticker for short) is a new-type localization medical instrument in 2020. Our study aims to explore the clinical value of a new lesion stickers in breast lesion surface localization via comparison of the sticker and marker pen localization methods.@*METHODS@#This was a prospective cohort study. It was conducted in 67 patients who needed breast lesion surface localization before biopsy. The patients were randomly assigned into 2 groups. One group of patients used marker pen to mark breast lesion surface location by ultrasonography. The other group of patients used stickers. Patients labeled with markers on skin were swabbed agents before marking. Then the markers were checked by ultrasound scan. If the surface positions of breast lesion were not correct, the above procedure was repeated. In the sticker group, the stickers were released synchronously after the lesions were detected by ultrasound scan. Then locations were checked via scanning hole. If the surface positions of breast lesion were not correct, the above procedure was repeated. The accuracy of positioning, the length of positioning time and satisfaction of patients between the 2 groups were compared. The length of positioning time was calculated from the time when ultrasound detected the lesion to the time when the surface position of breast lesion was confirmed. The total score of patients' satisfaction was 5 points according to Service Quality Evaluation of SERVQUAL Scale, including sonographers' service attitude and their technical proficiency, other medical staffs' service attitude and their technical proficiency, hospital service procedures, positioning comfort, and positioning effects.@*RESULTS@#All 67 patients were females, aged 18-66 (39.73±13.10). There were 35 patients in the marker pen group and 32 patients in the sticker group. The time length of group used marker pen to localization was 22-88 (52.20±2.90) s, and the sticker group was 3-15 (9.22±0.58) s in length. The length of positioning time for the stickers was significantly shorter than that of the marker (P<0.01). Both methods were accurate in the surface localization of lesions before operation. The total scores of patients' satisfaction was 4-5 (4.92±0.02) in the stickers group, and 1-5 (3.35±0.10) in the marker pen group. The patients' satisfaction scores with the sticker were significantly higher than those with the marker pen (P<0.01). The length of positioning time and patients' satisfication scores for sonographer with 20 years' working experience were shorter and higher than those of sonographer with 10 years' working experience, respectively (both P<0.05).@*CONCLUSIONS@#The new breast lesion positioning stickers have more advantages than the marker pen in localization efficiency. It could reduce the workload of medical workers and increase patients' satisfaction to some extent. The stickers can be used not only in the breast lesions surface localization, but also in the skin location of pleural effusion and ascites, the skin location of surface masses, the skin location of thyroid nodule, and many other clinical marker areas, to further expand the scope of clinical application and value of the stickers.
Subject(s)
Female , Humans , Male , Breast/diagnostic imaging , Breast Neoplasms/diagnostic imaging , Prospective Studies , SkinABSTRACT
As a common soil-borne nematode, hookworm is mainly parasitized in the intestine, and the clinical manifestations of hookworm infections mainly include gastrointestinal symptoms and iron-deficiency anemia. In addition, hookworm may be also parasitized in other organs in addition to gastrointestinal system, resulting in development of disorders in other systems. Proteinuria caused by hookworm infections is rare and easy to be misdiagnosed in clinical practices. Hereby, the diagnosis and treatment of a case of proteinuria associated with hookworm infections was reported, in order to increase the understanding of hookworm infection-associated proteinuria among clinicians.
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Objective: To explore the clinical value of von Willebrand Factor (vWF) and VITRO score (vWF:Ag/platelet count) in assessing disease progression in patients with HBV infection. Methods: Randomly collect relevant clinical data of 308 patients with HBV infection (including 154 cases of chronic hepatitis B, 66 cases of hepatitis B cirrhosis in compensatory period, 88 cases of hepatitis B cirrhosis in decompensated period) from December 1, 2018 to January 5, 2021 in the Second Affiliated Hospital of Chongqing Medical University. The vWF values are measured by a uniform optical method, and all data are included using a uniform standard. Analyze the difference and significance of plasma vWF level and VITRO score in chronic hepatitis B, hepatitis B cirrhosis in the compensatory phase and decompensated phase. Results: The plasma vWF level and VITRO score of the chronic hepatitis B group were (139.47±76.44) and (0.86±0.8), respectively, and the hepatitis B cirrhosis compensated group was (164.95±67.12 and 1.44±1.14), respectively. Hepatitis cirrhosis decompensated group were (317.48±103.32 and 6.81±4.98), respectively; plasma vWF level and VITRO score increased with the progression of HBV infection, and the difference was statistically significant (F=133.669,P=0.000F=137.598,P=0.000).The plasma vWF level and VITRO score in patients with hepatitis B cirrhosis were (185.65±85.07 and 2.3±2.37) in the Child-Pugh A group, (304.74±105.81 and 6.37±5.19) in the B grade group, and (369.48±73.238.28±5.38) in the C grade group; plasma vWF level and VITRO score in patients with hepatitis B cirrhosis increased with the increase of Child-Pugh grade, and the difference was statistically significant (F=60.236, P=0.000F=32.854, P=0.000). The area under the curve (AUC) of plasma vWF level and VITRO score for diagnosing the decompensated stage of hepatitis B cirrhosis were 0.897 [95% confidence interval (CI): 0.855-0.940, P<0.01], 0.949 [95% CI: 0.916-0.982, P<0.01). When the vWF level and VITRO score were taken as cut-off values of 238.5% and 1.65, respectively, the sensitivity of diagnosing the decompensated stage of hepatitis B cirrhosis was 79.5% and 94.3%, the specificity was 92.3% and 87.7%, and the positive predictive value was 80.5% and 94.3%, the negative predictive value was 91.9% and 97.5%, and the diagnostic accuracy was 88.6% and 89.3%. Among the patients with decompensated hepatitis B cirrhosis, the level of vWF in the group with gastrointestinal bleeding (367.24±68.29)% was significantly higher than that in the group without gastrointestinal bleeding (286.15±109.69)%, and the difference was statistically significant (P<0.001) The VITRO score of the group with gastrointestinal bleeding (9.12±5.4) was significantly higher than that of the group without gastrointestinal bleeding (5.36±4.13), and the difference was statistically significant (P<0.01). The vWF level in the spontaneous peritonitis group was (341.73±87.92)% higher than that in the non-spontaneous peritonitis group (296.32±111.74)%, and the difference was statistically significant (P<0.05). There was no statistical difference in VITRO score between the two groups. significance. Conclusion: Plasma vWF level and VITRO score can evaluate the progression of liver disease and the degree of decompensation of liver cirrhosis in patients with HBV infection, and have a predictive effect on various complications after decompensation of liver cirrhosis, and have certain guiding significance for early intervention measures.
Subject(s)
Humans , Disease Progression , Gastrointestinal Hemorrhage/etiology , Hepatitis B/complications , Hepatitis B virus , Hepatitis B, Chronic/diagnosis , Liver Cirrhosis/virology , Peritonitis/complications , von Willebrand Factor/analysisABSTRACT
Objective: To establish a three-dimensional model of middle ear-eustachian tube based on Chinese digital visual human dataset, and the deformation and pressure changes of the middle ear-eustachian tube system after eustachian tube opening are simulated by computer numerical simulation. Methods: The first female Chinese Digital Visual Human data was adopted. The images were imported by Amira image processing software, and the images were segmented by Geomagic software to form a three-dimensional model of middle ear-eustachian tube system, including eustachian tube, tympanum, tympanic membrane, auditory ossicles, and mastoid air cells system. The 3D model was imported into Hypermesh software for meshing and analysis. The structural mechanics calculation was carried out by Abaqus, and gas flow was simulated by Xflow. The tissue deformation and middle ear pressure changes during eustachian tube opening were numerically simulated by fluid-solid coupling algorithm. Several pressure monitoring points including tympanum, mastoid, tympanic isthmus, and external auditory canal were set up in the model, and the pressure changes of each monitoring point were recorded and compared. Results: In this study, a three-dimensional model of middle ear-eustachian tube and a numerical simulation model of middle ear ventilation were established, including eustachian tube, tympanum, mastoid air cells, tympanic membrane, and auditory ossicles. The dynamic changes of the model after ventilation could be divided into five stages according to the pressure. In addition, the pressure changes of tympanum and tympanic isthmus were basically synchronous, and the pressure changes of mastoid air cells system were later than that of tympanum and tympanic isthmus, which verified the pressure buffering effect of mastoid. The extracted pressure curve of the external auditory canal was basically consistent with that of tympanometry in terms of value and trend, which verified the effectiveness of the model. Conclusions: The numerical simulation model of middle ear-eustachian tube ventilation established in this paper can simulate the tissue deformation and middle ear pressure changes after eustachian tube opening, and its accuracy and effectiveness are also verified. This not only lays a foundation for further research, but also provides a new research method for the study of middle ear ventilation.
Subject(s)
Female , Humans , China , Ear, Middle , Eustachian Tube , Human Body , Middle Ear VentilationABSTRACT
Pulp loss is accompanied by the functional impairment of defense, sensory, and nutrition supply. The approach based on endogenous stem cells is a potential strategy for pulp regeneration. However, endogenous stem cell sources, exogenous regenerative signals, and neovascularization are major difficulties for pulp regeneration based on endogenous stem cells. Therefore, the purpose of our research is to seek an effective cytokines delivery strategy and bioactive materials to reestablish an ideal regenerative microenvironment for pulp regeneration. In in vitro study, we investigated the effects of Wnt3a, transforming growth factor-beta 1, and bone morphogenetic protein 7 (BMP7) on human dental pulp stem cells (h-DPSCs) and human umbilical vein endothelial cells. 2D and 3D culture systems based on collagen gel, matrigel, and gelatin methacryloyl were fabricated to evaluate the morphology and viability of h-DPSCs. In in vivo study, an ectopic nude mouse model and an in situ beagle dog model were established to investigate the possibility of pulp regeneration by implanting collagen gel loading BMP7. We concluded that BMP7 promoted the migration and odontogenic differentiation of h-DPSCs and vessel formation. Collagen gel maintained the cell adhesion, cell spreading, and cell viability of h-DPSCs in 2D or 3D culture. The transplantation of collagen gel loading BMP7 induced vascularized pulp-like tissue regeneration in vivo. The injectable approach based on collagen gel loading BMP7 might exert promising therapeutic application in endogenous pulp regeneration.
Subject(s)
Animals , Dogs , Humans , Mice , Bone Morphogenetic Protein 7/pharmacology , Cell Differentiation , Cells, Cultured , Collagen/pharmacology , Dental Pulp , Endothelial Cells , Gelatin , Methacrylates , Regeneration , Stem CellsABSTRACT
Objective:To retrospectively analyze the clinical characteristics of elderly patients with anti-MDA5 antibody-positive dermatomyositis.Methods:Data of 62 patients with anti-MDA5 antibody-positive dermatomyositis admitted to Second Xiangya Hospital from May 2016 to December 2019 were collected and patients were divided into an elderly group(≥60 years old, 17 cases)and a non-elderly group(<60 years old, 45 cases). The clinical manifestations, laboratory test resuls, treatment and prognosis of the patients in both groups were statistically analyzed.Results:A total of 62 patients with anti-MDA5 antibody-positive dermatomyositis were included in this study, including 17 elderly patients(27.4%)with an average age of(65.5±5.3)years and 45 non-elderly patients(72.6%)with an average age of(46.5±8.4)years.Compared with non-elderly patients, older patients had a shorter disease duration[(1.6±1.0)months vs.(3.7±3.3)months, t=3.883, P<0.001], a higher proportion of patients with exertional dyspnea(15/17 or 88.2% vs.26/45 or 57.8%, χ2=5.11, P=0.024)and with combined positive anti-Ro-52 antibodies(15/17 or 88.2% vs.26/45 or 57.8%, χ2=5.11, P=0.024), and a higher mortality rate[(12/17 or 70.6%) vs.(8/45 or 17.8%, χ2=15.748, P<0.001)]. In contrast, fewer elderly patients than non-elderly patients had the Heliotrope's sign(9/17 or 41.2% vs.38/45 or 57.8%), χ2=5.07, P=0.024). Conclusions:Elderly patients with anti-MDA5 antibody-positive dermatomyositis have a unique clinical phenotype with an acute onset, atypical rashes, severe pulmonary lesions, making treatment difficult, and have a poor prognosis.
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Objective:To observe the effect of Jianpi Xiaoai prescription on long non-coding RNA Hox transcript antisense intergenic RNA (lncRNA HOTAIR)/Janus kinase 2 (JAK2) /signal transducer and activator of transcription 3 (STAT3) signaling pathway and to explore the potential mechanism of Jianpi Xiaoai prescription in suppressing the metastasis of colon cancer. Method:The expression of lncRNA HOTAIR in different cells was analyzed. Following the treatment of HCT116 cells with 10%,15%,and 20% Jianpi Xiaoai prescription -containing serum, the invasive ability of Jianpi Xiaoai prescription on HCT116 cells was assessed by transwell assay. The mRNA expression levels of lncRNA HOTAIR,JAK2,and STAT3 were measured by Real-time polymerase chain reaction (Real-time PCR), and the protein expression levels of JAK2, phosphorylated STAT3 (p-STAT3) and STAT3 by Western blot. Result:The highest expression of lncRNA HOTAIR was detected in HCT116 cells. Compared with the blank group, each Jianpi Xiaoai prescription group exhibited a decreased number of invasive cells (<italic>P</italic><0.05, <italic>P</italic><0.01). The relative JAK2 mRNA expression in the middle-dose Jianpi Xiaoai prescription group was down-regulated (<italic>P</italic><0.05), and the relative lncRNA HOTAIR mRNA expression in the middle- and high-dose Jianpi Xiaoai prescription groups and the relative JAK2 mRNA expression in the high-dose Jianpi Xiaoai prescription group were remarkably down-regulated (<italic>P</italic><0.01). Compared with the blank group,the relative p-STAT3 protein expression was down-regulated in the middle-dose Jianpi Xiaoai prescription group (<italic>P</italic><0.05), and the relative JAK2 protein expression in the middle- and high-dose Jianpi Xiaoai prescription groups and the relative p-STAT3 protein expression in the high-dose Jianpi Xiaoai prescription group were remarkably down-regulated (<italic>P</italic><0.01). Conclusion:Jianpi Xiaoai prescription effectively inhibits the metastasis of colon cancer cells, which may be related to the inhibition of lncRNA HOTAIR/JAK2/STAT3 signaling pathway.
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Objective:To observe the effect of modified Shuyuwan in amyloid precursor protein/ presenilin 1 (APP/PS1) dementia mice on cognitive and memory impairment and to explore its mechanism. Method:The 40 APP/PS1 mice were divided into model group (given Physiological saline), low and high-dose modified Shuyuwan (14,64 g·kg<sup>-1</sup>)group, and donepezil group (1 mg·kg<sup>-1</sup>) and 10 wild mice were set as the blank control group (given Physiological saline). All of the mice were administered intragastrically for 35 days. The memory and space exploration ability of mice was detected by Morris water maze, the morphology of mouse hippocampal neurons were observed by Nissl staining. The deposition of <italic>β </italic>amyloid 1-42(A<italic>β</italic><sub>1-42</sub>) in mouse hippocampus was detected by immunohistochemistry, and the expression of ionized calcium-binding adapter molecule 1(Iba1), a marker of hippocampal microglia (MG) and Nitric oxide synthase(iNOS), a marker of actived MG, were detected by immunofluorescence. The protein expression of NLR family pyrin domain containing 3(Nlrp3), Apoptosis-associated speck-like protein containing a Caspase-recruitment domain (ASC), cysteine protease-1(Caspase-1)and interleukin-1 beta (IL-1<italic>β</italic>) were detected by Western blot, and the expression of IL-1<italic>β</italic>, tumor necrosis factor-<italic>α</italic>(TNF-<italic>α</italic>)and interleukin-18 (IL-18) mRNA were detected by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). Result:Compared with the blank control group, the memory and space exploration ability of the model group were significantly reduced (<italic>P</italic><0.05), the number of hippocampal neurons decreased, the deposition of A<italic>β</italic><sub>1-42</sub> increased, the markers of actived MG Iba1,iNOS increased, the protein expression of Nlrp3, ASC, Caspase-1, IL-1<italic>β</italic> increased significantly (<italic>P</italic><0.05), and the mRNA expression of IL-1<italic>β</italic>, IL-18, and TNF-<italic>α</italic> increased significantly (<italic>P</italic><0.05). Compared with model group, the Chinese medicine group can improve the APP/PS1 mice's space exploration ability and memory ability (<italic>P</italic><0.05), increase the number of hippocampal neurons, reduce A<italic>β</italic><sub>1-42</sub> deposition, reduce the activation of MG, and reduce the protein expression of Nlrp3, ASC, Caspase-1 and IL-1<italic>β</italic> (<italic>P</italic><0.05), and reduced the expression of IL-1<italic>β</italic> mRNA (<italic>P</italic><0.05). Conclusion:Modified Shuyuwan can reduce the expression of IL-1<italic>β</italic> and other inflammatory factors in the hippocampus of APP/PS1 mice by inhibiting the Nlrp3/ASC/Caspase-1 pathway, and relieve nerve inflammation and pathological injury of AD.
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A 69-year old man presented with high-risk metastatic prostate cancer. After 7 months of androgen deprivation therapy (ADT), he progressed to metastatic castration resistant prostate cancer. We suggested him comprehensive therapy, including Abiraterone, chemo-therapy, radio-therapy, platinum chemo-therapy and Enzalutamide, which proved effective with his long term survival.