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The main protease (Mpro) of SARS-CoV-2 is an attractive target in anti-COVID-19 therapy for its high conservation and major role in the virus life cycle. The covalent Mpro inhibitor nirmatrelvir (in combination with ritonavir, a pharmacokinetic enhancer) and the non-covalent inhibitor ensitrelvir have shown efficacy in clinical trials and have been approved for therapeutic use. Effective antiviral drugs are needed to fight the pandemic, while non-covalent Mpro inhibitors could be promising alternatives due to their high selectivity and favorable druggability. Numerous non-covalent Mpro inhibitors with desirable properties have been developed based on available crystal structures of Mpro. In this article, we describe medicinal chemistry strategies applied for the discovery and optimization of non-covalent Mpro inhibitors, followed by a general overview and critical analysis of the available information. Prospective viewpoints and insights into current strategies for the development of non-covalent Mpro inhibitors are also discussed.
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Objective To evaluate the effectiveness of a hospital logistics operation and management based on the"one center,four platforms"model.Methods In line with the grading evaluation standards for hospital intelligent management,we used technologies such as big data,Internet of Things,Internet Plus,and artificial intelligence to develop a"one center,four platforms"model.This model consisted of a logistics intelligent operation and maintenance management center,an equipment control information platform,a security prevention information platform,an energy consumption monitoring information platform,and an operation management information platform.Results The equipment fault resolution capability,enhanced by the"smart linkage",showed a significant improvement.In 2022,false alarms decreased by 28.63%compared to 2021,with high-level and ordinary-level alarms decreasing by 69.53%and 33.15%,respectively.The"one-stop"logistics service capability was signifi-cantly improved,as indicated by a 2.92%decrease in maintenance frequency in 2022 compared to 2021.This improvement was further reflected in the quality of maintenance and a decrease in the repeated maintenance occurrences.The energy consumption control capability,based on the"data mining",showed a significant improvement,with an 8.71%year-on-year decrease in en-ergy expenditure of ten thousand yuan in 2022 compared to 2021.Conclusion The"one center,four platforms"model can sig-nificantly enhance the efficiency of logistics operation and maintenance management.
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ObjectiveTo analyze the antidepressant quality markers(Q-Marker) of Bupleuri Radix(BP) before and after vinegar-processing by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS), multivariate statistical analysis and network pharmacology. MethodUPLC-Q-TOF-MS was used to analyze the chemical basis of raw and vinegar-processed products of BP, and principal component analysis(PCA) orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to identify the differential components in BP that changed significantly before and after vinegar-processing, which were regarded as candidate quality markers(Q-Marker). Then the disease-drug-component-target network related to antidepressant effect of BP was constructed by network pharmacology, and the antidepressant Q-Marker of raw and vinegar-processed products of BP was determined. Rats were randomly divided into blank group, model group, fluoxetine group(2.67 mg·kg-1) and total saponin group(0.72 mg·kg-1), except the blank group, rats in the other groups were subjected to chronic unpredictable mild stress(CUMS). Three weeks after the start of modeling, rats in each administration group were given the corresponding dose of drugs once a day for 4 weeks, and rats in the blank and model groups were given normal saline with dose of 10 mL·kg-1. At 1 day before modeling, 21 days and 28 days after administration, body mass weighing, sucrose preference test and open field test were performed on each group . After 28 days of administration, real-time fluorescence quantitative polymerase chain reaction(Real-time PCR) was used to detect the mRNA expression levels of phosphatidylinositol 3-kinase(PI3K), protein kinase B(Akt), mammalian target of rapamycin(mTOR), glycogen synthase kinase-3β(GSK-3β), forkhead box transcription factor O3a(FoxO3a) and β-catenin in hippocampal tissues of rats in each group, while protein expression levels of PI3K, Akt, mTOR and FoxO3a in hippocampal tissues of rats in each group were detected by Western blot. ResultThere were 19 components in BP showed significant changes before and after vinegar-processing, and 9 components such as saikosaponin A, saikosaponin B1, saikosaponin B2, saikosaponin C and saikosaponin D were identified as potential Q-Marker through S-plot differential marker screening. Combined with the disease-drug-component-target network, saikosaponin A, saikosaponin B1, saikosaponin B2 and saikosaponin D were identified as antidepressant Q-Marker of raw and vinegar-processed products of BP. According to the results of pharmacodynamic tests, after 28 d of administration, compared with the blank group, the body mass, sucrose preference index and open field total score of rats in model group, fluoxetine group and total saponin group decreased significantly(P<0.01). Compared with the model group, the body mass, sucrose preference index and open field total score in total saponin group increased significantly(P<0.01). Compared with the blank group, mRNA expression levels of PI3K, Akt, mTOR and β-catenin in hippocampus of rats in the model group decreased significantly(P<0.05), while mRNA expression levels of GSK-3β and FoxO3a increased significantly(P<0.05). Compared with the model group, mRNA expression levels of PI3K, Akt, mTOR and β-catenin in hippocampus of rats in the total saponin group were increased significantly(P<0.05), while mRNA expression levels of GSK-3β and FoxO3a decreased significantly(P<0.05). Compared with the blank group, the protein expression levels of Akt and mTOR in hippocampus of the model group decreased significantly(P<0.01), while the protein expression levels of PI3K and FoxO3a increased significantly(P<0.01). Compared with the model group, the expression level of Akt in hippocampus of the total saponin group increased significantly(P<0.01), the mTOR expression level was increased but not statistically significant, while the protein expression levels of PI3K and FoxO3a decreased significantly(P<0.01). ConclusionThe chemical constituents of BP changed greatly after vinegar-processing, and the antidepressant Q-Marker of raw and vinegar-processed products of BP was determined by chemical basis, pharmacodynamics, network pharmacology and signaling pathway, which provided a reference for further research on quality control, pharmacodynamic substance basis and processing mechanism of BP.
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BACKGROUND: Sleep disorders significantly affect the quality of life in Parkinson disease (PD) patients. Deep brain stimulation of the subthalamic nucleus has been reported to improve motor symptoms and decrease medication usage. However, the impact of subthalamic nucleus deep brain stimulation (STN-DBS) on sleep quality in PD patients remains to be definitively determined. This systematic review and meta-analysis, conducted following the preferred reporting items for systematic reviews and meta-analyses guidelines, aimed to clarify the effect of STN-DBS on sleep quality in PD patients. METHODS: A rigorous literature search identified 6 studies, including 1 randomized controlled trial and 5 self-controlled trials, totaling 154 patients who underwent deep brain stimulation, providing 308 pairs of data for analysis. Parkinson disease sleep scale was the primary measure of interest, while the Movement Disorder Society-sponsored revision of the unified Parkinson disease rating scale was documented in all trials. Study quality was assessed using the Newcastle-Ottawa scale. RESULTS: STN-DBS significantly improved Parkinson disease sleep scale scores (mean difference = 20.41, 95% CI: [13.03, 27.79], I² = 60.8%, P < .001), indicating enhanced sleep quality. Furthermore, a significant reduction in movement disorder society unified Parkinson disease rating scale part III scores postoperatively (mean difference = -12.59, 95% CI: [-14.70, -10.49], I² = 89.9%, P < .001) suggested improved motor function. PD medication usage was also significantly reduced postoperatively (mean difference = -314.71, 95% CI: [-468.13, -161.28], I² = 52.9%, P < .001). A sensitivity analysis confirmed the robustness of the main findings. The sample size was adequate, allowing for conclusive inferences. CONCLUSION: The present study, which comprises a comprehensive systematic review and meta-analysis, offers compelling evidence that STN-DBS can ameliorate sleep quality, augment motor function, and curtail medication consumption among individuals afflicted with PD.
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Estimulación Encefálica Profunda , Enfermedad de Parkinson , Núcleo Subtalámico , Humanos , Núcleo Subtalámico/fisiología , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/terapia , Calidad de Vida , Sueño/fisiología , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Objective:To investigate the application effect of blended teaching mode based on Rain Classroom in the course of nursing education.Methods:The nursing teaching class in 2019 was set as the observation group ( n=20), which adopted blended teaching mode combining classroom teaching and online learning of Rain Classroom platform. The teaching class with the same number of students in the same period in 2018 was set as the control group ( n=20), which implemented the traditional classroom teaching mode. SPSS 22.0 was used for statistical processing, and independent-samples t-test was used to analyze the results of seminar, simulated teaching and final theoretical examination of the two classes of students and the evaluation of the teaching effect of the course. Results:There was no significant difference between the two groups in the results of simulated teaching ( t=0.21, P = 0.834). The scores of seminar [(91.18±1.20), t=3.09, P<0.05] and final theoretical examination [(78.63±6.28), t=3.33, P<0.05] in the observation group were significantly higher than those in the control group. The scores of information retrieval and processing ability ( t=-3.33, P < 0.05), problem finding ability ( t=-2.17, P < 0.05), independent thinking ability ( t=-2.53, P < 0.05), knowledge integration ability ( t=-3.86, P < 0.001), self-learning ability ( t=-3.12, P<0.05), the sense of identity to the role of nursing teachers ( t=-2.53, P < 0.05), the awareness of active learning ( t=-3.13, P < 0.05) and the attitude of lifelong learning ( t=-4.46, P < 0.001) in the experimental group were higher than those in the control group. Conclusion:The blended teaching based on Rain Classroom is conducive to the cultivation of students' inquiry learning ability and deep learning of theoretical knowledge, and promotes the effective achievement of curriculum teaching objectives.
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At present, the diagnosis of sepsis associated-acute kidney injury (SA-AKI) mainly relies on monitoring urine volume or serum creatinine (SCr) levels. Due to decreased renal blood supply and the use of diuretics, the diagnosis is intrusive and non-specific. Early identification of the clinical process of SA-AKI and effective management can restore renal function as soon as possible and improve outcomes. This paper discusses the epidemiology, diagnostic limitations, pathophysiological mechanism, treatment and prognosis of SA-AKI. Approximately 30% of patients with sepsis were found to develop acute kidney injury (AKI), and 50% of patients with AKI in the intensive care unit (ICU) were found to have sepsis. Once a diagnosis of SA-AKI is made, close monitoring and timely organ support therapy should be combined to prevent further kidney injury. SA-AKI can be reversed early in the first week after admission, and the prognosis is good. The main mechanisms of organ injury in sepsis are reduced perfusion of bilateral glomeruli, impaired inflammatory response, metabolic adaptation and microcirculation. Etiological control and antibiotic application early play important roles in sepsis management. In addition, fluid resuscitation, vasopressors, early use of renal replacement therapy (RRT), and blood purification are important prognostic factors of SA-AKI.
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Objective To study and estimate the public dose constraint and the atmospheric radiation capacity of an isotope industrial park, and to provide a basis for management of radioactive effluent discharge in isotope industrial parks. Methods We collected the natural environment data, meteorological data, and population distribution and dietary data as well as the source terms of radioactive airborne effluents of an isotope industrial park. The public dose constraint value of the isotope industrial park was determined based on the natural environmental radiation hazard level. The atmospheric environmental radiation capacity of the industrial park was estimated by the all-pathways method. Results The public dose constraint value of the industrial park was 0.2 mSv/a. At the end of industrial park planning, the maximum individual effective dose to the public caused by airborne effluent discharge was 1.07×10−6 Sv/a, which accounted for 0.54% of the public dose constraint value. The proportions of discharges of airborne radionuclides to respective environmental radiation capacities ranged from 0.04% to 4.34%. Conclusion The determined public dose constraint value of the isotope industrial park can be used as the total radiation capacity of the regional atmospheric environment to constrain the discharge of radioactive effluents. The environmental radiation capacity of each radionuclide can be estimated by the all-pathways method considering the comprehensive impact of radionuclide discharges, which is suitable for the control and management of isotope production enterprises in industrial parks.
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Objective:To explore the effect of clinical nursing teacher training mode guided by deep learning theory.Methods:The clinical nursing teacher training mode was constructed under the guidance of deep learning theory and in combination with the characteristics of clinical nursing teachers, led and implemented by the university teacher development center. The questionnaire guided by Kirkpatrick Model was used to investigate clinical nursing teachers who had completed the five-stage training. The effects and differences in reaction, learning, behavior, and result levels were compared between the training objects in six training sessions. A total of 138 questionnaires were collected, of which 129 questionnaires were valid, with a response rate of 93.48%. The SPSS 22.0 was used to conduct analysis of variance or chi-square test.Results:On the reaction level, there were significant differences in the satisfaction of trainees in training time, examination form, and organization management ( P<0.05); on the learning level, the trainees had different opinions on the effect of training on promotion and improvement of clinical nursing quality ( P<0.05); on the behavior level, the training objects had different tasks in undergraduate classroom teaching and in hospital and medical association education and training ( P<0.05); on the result level, the clinical nursing teachers who completed the training all participated in different types of nursing teaching. Conclusion:The clinical nursing teacher training mode based on deep learning theory can significantly improve the teaching ability of clinical nursing teachers and promote their professional development.
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Objective:To explore the selection criteria of the donor for islet transplantation of Chinese people by analyzing the correlation between pancreas characteristics and success rate of islets isolation.Methods:Data from 113 cases of human islet isolation were collected. According to the result of islet isolation, the donors were divided into two groups, the success group(IEQ≥250 000, purification≥30%, and viability≥80%), and the failure group(IEQ<250 000, or purification<30%, or viability<80%). The modified Ricordi method was used to digest pancreas tissue, and the continuous density gradient method was performed to purify islets. The islets were identified by staining with the Dithizone(DTZ), the islets were analyzed for cell viability and purity.Results:The donor age in success group was significantly younger than failure group in the range of age eligible for this study( t=2.479, P=0.015). Pearson correlation showed that donor age was positively corelated with islet yield( r=-0.214, P=0.047). There was more fat on the pancreas surface in the successful islet isolation group( z=-2.007, P=0.045). The digestibility( t=2.133, P=0.035) and recovery rate( t=5.912, P=0.001) were elevated in success group. Conclusion:The pancreases from younger donors could obtain the higher-yielding islet, the pancreas with more surface fat or with higher weight was associated with islet isolation success in the scope covered by the inclusion criteria of this study.
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Malignant tumors, with the increasing crude morbidity and mortality year by year, have become the major diseases threatening human health. The conventional therapeutic drugs against tumors have serious adverse reactions, which can cause a heavy burden on patients. The active components of Chinese medicine can effectively inhibit tumor growth, improve the quality of life of patients, and have few toxic and side effects. Alkaloids of Chinese medicine are natural organic compounds widely existing in a variety of Chinese herbal medicines. In recent years, they have attracted more and more attention because of their anti-tumor effect. The anti-tumor mechanisms of alkaloids of Chinese medicine mainly include the induction of apoptosis, inhibition of tumor cell migration and invasion, suppression of proliferation, induction of autophagy of tumor cells, cell cycle arrest, inhibition of tumor angiogenesis, regulation of microRNA, and modulation of immunity. In addition, Chinese medicine alkaloids can also reverse tumor drug resistance and reduce the stemness of tumor stem cells. Alkaloids of Chinese medicine can regulate the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (p38 MAPK), mammalian target of rapamycin (mTOR), Notch, Hedgehog, Wnt/β-catenin, and other signaling pathways to participate in the processes of tumor proliferation, invasion and metastasis, autophagy and apoptosis, and affect the occurrence and development of tumors in multiple links and ways. The derivatives and nano-preparations of alkaloids can improve the solubility, utilization, and anti-tumor activity of alkaloids, bringing a broader prospect for the clinical application of alkaloids. This review summarized the recent anti-tumor research on alkaloids, their representative derivatives, and nano-preparations to provide references for the in-depth research on the anti-tumor effect of alkaloids.
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OBJECTIVE@#To study the effect of various intracanal materials on the accuracy of oral maxillofacial cone-beam computed tomography (CBCT) for the diagnosis of vertical root fracture (VRF).@*METHODS@#A total of twenty-four structurally intact single root canal dried and isolated teeth extracted for orthodontic treatment or periodontal disease were collected. The teeth were decrowned along the cemento-enamel junction (CEJ) and then used as samples for the study after conventional root canal preparation and post preparation. The 24 samples were divided into two groups with 12 samples in each group. Group A was the control group (no VRF group). According to intracanal materials, they were divided into five subgroups: blank group, fiber post group, gutta-percha point group, titanium post group and gold-palladium post group. Group B was the experimental group (VRF group), and subgroups were grouped as above. The VRF model was prepared by a unified method in the VRF group: the root was completely fractured in the buccolingual direction with a custom root canal nail and then cemented and reset. The control group was not subjected to the simulation of VRF. Titanium post and gold-palladium post were made according to the individuality of the root canal preparation, and the tightness of the post to the root canal wall was confirmed by X-ray radiograph. Then all the samples were scanned by CBCT in the isolate swine mandibular alveolar sockets. The diagnostic accuracy was statistically analyzed via blind interpretation by experienced endodontic specialists and oral and maxillofacial medical imaging specialists.@*RESULTS@#The accuracy of the diagnosis of VRF in the blank group, fiber post group, gutta-percha point group, titanium post group, and gold-palladium post group in CBCT was 95.83%, 91.67%, 87.50%, 79.17%, and 45.83%, respectively. Compared with the blank group, the differences were not statistically significant in the fiber post group (P>0.999), the gutta-percha point group (P=0.500) and the titanium post group (P=0.125). The lowest diagnostic accuracy of VRF was found in the gold-palladium post group, and the difference was statistically significant compared with all other groups (P < 0.001).@*CONCLUSION@#Various intracanal materials have different degrees of influence on the diagnostic accuracy of VRF diagnosis in CBCT. The influence of fiber post, gutta-percha point and titanium post was small, while the influence of gold-palladium post was significant.
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Animales , Tomografía Computarizada de Haz Cónico/métodos , Oro , Gutapercha , Paladio , Porcinos , Titanio , Fracturas de los Dientes/diagnóstico por imagen , Raíz del Diente/lesiones , Reproducibilidad de los ResultadosRESUMEN
Objective To explore influences of the taper and connecting rib form on supporting performance of the stent, and provide an important scientific basis for structural design and clinical selection of the tapered stent. Methods A nonlinear finite element model for radial support performance of a novel balloon-expandable tapered stent was constructed, and the radial stiffness (RS) and stress distributions of the stent at different tapers (0°, 0.565°and 1.13°) and with different structural forms of stent linker (V-shape, I-shape, C-shape, S-shape, M-shape) were analyzed by plane compression. The relationship between structural design of the vascular stent and its radial support performance was studied. Results The RS of 0°stent, 0.565°stent, 1.13° stent was 2.51, 1.61, 0.85 N/mm, respectively. The RS of 0.565°stent and 1.13° stent was 35.86% and 66.14% lower than that of 0°stent (round straight stent), respectively. Except that the RS of C-shape linker stent was 1.48 N/mm, the RS of I, M, S and V-shape linker stents was not significantly different, which was 2.51, 2.61, 2.41, 2.52 N/mm, respectively, indicating that radial compression resistance of these four linker stents was almost the same. Conclusions Compared with traditional round straight stents, the RS of tapered stents will decrease, and the RS of stents will gradually decrease with the the taper increasing. Among all stent types in this study, except C-shape linker stents, the RS of other linker shapes has little effect on the RS of stents. The radial support performance of the stent can be improved by reducing the taper of the tapered stent, without changing the form of stent connecting ribs.
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Microbial transformation is an efficient enzymatic approach for the structural modification of exogenous compounds to obtain derivatives. Compared with traditional chemical synthesis, the microbial transformation has in fact the undoubtable advantages of strong region-and stereo-selectivity, and a low environmental and economic impact on the production process, which can achieve the reactions challenging to chemical synthesis. Because microbes are equipped with a broad-spectrum of enzymes and therefore can metabolize various substrates, they are not only a significant route for obtaining novel active derivatives, but also an effective tool for mimicking mammal metabolism in vitro. Artemisinin, a sesquiterpene with a peroxy-bridged structure serving as the main active functional group, is a famous antimalarial agent discovered from Artemisia annua L. Some sesquiterpenoids, such as dihydroartemisinin, artemether, and arteether, have been developed on the basis of artemisinin, which have been successfully marketed and become the first-line antimalarial drugs recommended by WHO. As revealed by pharmacological studies, artemisinin and its derivatives have exhibited extensive biological activities, including antimalarial, antitumor, antiviral, anti-inflammatory, and immunomodulatory. As an efficient approach for structural modification, microbial transformation of artemisinin and its derivatives is an increasingly popular strategy that attracts considerable attention recently, and numerous novel derivatives have been discovered. Herein, this paper reviewed the microbial transformation of artemisinin and its artemisinin, including microbial strains, culture conditions, product isolation and yield, and biological activities, and summarized the advances in microbial transformation in obtaining active derivatives of artemisinin and the simulation of in vivo metabolism of drugs.
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Animales , Antimaláricos/farmacología , Antivirales , Arteméter , Artemisininas , MamíferosRESUMEN
Background and Purpose: Hypoxia is one of the basic characteristics of the physical microenvironment of solid tumors. The relationship between radiotherapy and hypoxia is complex. However, there is no radiosensitivity prediction model based on hypoxia genes. We attempted to construct a radiosensitivity prediction model developed based on hypoxia genes for lower-grade glioma (LGG) by using weighted correlation network analysis (WGCNA) and least absolute shrinkage and selection operator (Lasso). Methods: In this research, radiotherapy-related module genes were selected after WGCNA. Then, Lasso was performed to select genes in patients who received radiotherapy. Finally, 12 genes (AGK, ETV4, PARD6A, PTP4A2, RIOK3, SIGMAR1, SLC34A2, SMURF1, STK33, TCEAL1, TFPI, and UROS) were included in the model. A radiosensitivity-related risk score model was established based on the overall rate of The Cancer Genome Atlas (TCGA) dataset in patients who received radiotherapy. The model was validated in TCGA dataset and two Chinese Glioma Genome Atlas (CGGA) datasets. A novel nomogram was developed to predict the overall survival of LGG patients. Results: We developed and verified a radiosensitivity-related risk score model based on hypoxia genes. The radiosensitivity-related risk score served as an independent prognostic indicator. This radiosensitivity-related risk score model has prognostic prediction ability. Moreover, a nomogram integrating risk score with age and tumor grade was established to perform better for predicting 1-, 3-, and 5-year survival rates. Conclusions: We developed and validated a radiosensitivity prediction model that can be used by clinicians and researchers to predict patient survival rates and achieve personalized treatment of LGG.
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Objective @#To investigation of the interaction between interstitial cells of Cajal (ICCs) and connexin 43 ( Cx43) in bladder contraction and its significance.@*Methods @#Eighty male guinea pigs were randomly divided into blank control group,Glivec group,Gap27 group and Glivec + Gap27 group.Four groups of guinea pigs were per- fused with saline,Glivec,Gap 27,and Glivec + Gap 27 every morning for 2 months.Success of urodynamic testing model after 2 months.Bladder tissue was collected for an in vitro muscle strip test to detect muscle contraction in each group.Correlation between c-Kit and Cx43 was detected by immunofluorescence.The interaction between c- Kit and Cx43 in the bladder was further validated by qRT-PCR and Western blot.Ultrastructural changes in the muscle layer of the bladder were observed by electron microscopy. @*Results @#Urodynamics revealed increased blad- der compliance in the experimental group compared to the blank control group (P<0. 05) ; bladder compliance increased in the Glivec + Gap27 group compared to the Glivec and Gap27 groups (P<0. 01) .In vitro muscle strip experiments revealed that the frequency and tone of bladder muscle strip contractions were lower in the experimental group compared to the blank control group (P<0. 05) ,and that muscle strip contractions were weaker in the ex- perimental group after administration of acetylcholine (ACH) compared to the control group(P<0. 05) .Immuno- fluorescence showed that c-Kit was co-expressed with Cx43 on ICCs cells.qRT-PCR and Western blot suggested that the protein expression level and gene expression level of Cx43 in bladder tissues were lower after inhibition of c-Kit than in the blank control (P<0. 05) ; after inhibition of Cx43,the protein expression level and gene expres- sion level of c-Kit in bladder tissues the levels of c-Kit protein expression and gene expression in bladder tissues were lower than those in the blank control group (P<0. 05) .Electron microscopy revealed that the mitochondrial structure of bladder smooth muscle was disrupted after simultaneous inhibition of c-Kit and Cx43.@*Conclusion@#Cx43 is expressed on bladder ICCs and the two may be jointly involved in regulating bladder contractile function ; the joint reduction of Cx43 and c-Kit may have disrupted the mitochondria of bladder smooth muscle,affecting its function and consequently bladder contractile function.
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Objective @#To investigate the effect of the combination of stem cell leukemia(SCL)recombinant lentivirus and connexin 43 ( Cx43 ) recombinant lentivirus on the function of diabetic cystipathy ( DCP) in guinea pigs.@*Methods @#After 90 healthy guinea pigs were fed normally for 1 week, streptozotocin(STZ)was injected intraperito⁃ neally at 200 mg/kg in a single dose, and random blood glucose was monitored weekly. After 12 weeks of normal feeding, 40 guinea pigs meeting the criteria were screened by urodynamic examination and randomly divided into 4 groups: diabetic group, SCL group, Cx43 group, and SCL + Cx43 group. In the diabetic group, 0. 2 ml of empty lentivirus without gene was instilled into the bladder through the urethra, in the SCL and Cx43 groups, 0. 2 ml of SCL lentivirus and Cx43 lentivirus were instilled using the same method, in the SCL + Cx43 lentivirus group, 0. 2 ml of each SCL and Cx43 lentivirus was instilled through the urethra. After 14 days of transfection, urodynamic examination was performed, and then the guinea pigs were executed after the examination, and the bladders were quickly removed for frozen bladder sections and fluorescent double staining. @*Results @#There were no differences in urodynamic examinations between the SCL and Cx43 groups compared to the diabetic group( P > 0. 05 ) . Urodynamic examination in the SCL + Cx43 group showed improvement in detrusor pressure, abdominal pressure and bladder pressure compared to the diabetic group(P < 0. 05) . In laser confocal experiments, the number of interstitial cells of Cajal (ICC) was reduced in the diabetic group, and the spindle structure and cell protrusions were obviously destroyed and appeared in a state of cell lysis. In the SCL and Cx43 groups, there was an improvement in the spindle structure and cell protrusion of ICC⁃like cells, and there was no significant change in the number of cells. In the SCL + Cx43 group, there was an increase in the number of ICC⁃like cells, a significant improvement in the spindle structure and cell protrusion, and the formation of ICC⁃dimers.@*Conclusion @#Transurethral co⁃infusion of SCL and Cx43 gene recombinant lentivirus can be successfully transfected in guinea pig DCP bladder, which can restore the number and structure of damaged ICC cells and form ICC dimer structure, improve the pressure of diabetic bladder forced urinary muscle, improve the weakness of urination, ventral pressure voiding and other characteristics. It provides a new direction for the treatment of DCP.
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Objective:To establish a method for quantitative analysis of the active ingredients including salidroside, rosarin and rosavin and content determination in Rhodiola rosea at different harvest months. Methods:HPLC was used on an X selectHSS T3 (250 mm×4.6 mm, 5 μm) column with mobile phase consisting of methol-acetonitrile-phosphoric acid (0.05%) aqueous solution for gradient elution at a flow rate of 1 ml/min. The wavelength was detected at 275 nm (salidroside) and 254 nm (rosarin, rosavin). The column temperature was set at 30 ℃ and the injection volume was 5 μl.Results:The peak areas of Salidroside, rosarin and rosavin showed good linear relationships ( r > 0.999) with the content in the ranges of 44-1 420, 10-307 and 18-573 μg, respectively. The method was precise, stable, repeatable and the sample recovery test all well satisfied the requirements of quantitative analysis. The highest accumulation of the active ingredients was observed in Rhodiola rosea in September and the content of salidroside, rosarin and rosavin were 0.66, 0.07 and 0.53 mg/g, respectively. Conclusion:This method is simple and rapid to evaluate the content of active ingredients in Rhodiola rosea.
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Objective:To investigate the changes of quadriceps femoris thickness with the length of stay in intensive care unit (ICU) in patients with sepsis, and to evaluate the diagnostic value of muscle changes in mortality.Methods:A prospective study was conducted, and 92 patients with sepsis who were admitted to the ICU of the Affiliated Hospital of Jining Medical College from January 2020 to December 2021 were enrolled. The thickness of quadriceps femoris [including the quadriceps femoris muscle thickness at the midpoint of the anterior superior iliac spine and the upper edge of the patella (M-QMLT), and at the middle and lower 1/3 of the patella (T-QMLT)] measured by ultrasound 1 day (D1), 3 days (D3), and 7 days (D7) after admission to the ICU were collected. The atrophy rate of quadriceps femoris was calculated 3 and 7 days after admission to the ICU compared with 1 day [(D3-D1)/D1 and (D7-D1)/D1, (TD3-TD1)/TD1 and (TD7-TD1)/TD1, respectively]. The demographic information, underlying diseases, vital signs when admission to the ICU and in-hospital mortality of all patients were recorded, and the differences of the above indicators between the two groupswere compared. Multivariate Logistic regression was used to analyze the influence of quadriceps femoris muscle thickness and atrophy rate on in-hospital mortality of septic patients. The receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of quadriceps femoris muscle thickness and atrophy rate on in-hospital mortality of septic patients.Results:A total of 92 patients with severe sepsis were included, of which 41 patients died in hospital, 51 patients discharged. The in-hospital mortality was 44.6%. The muscle thickness of quadriceps femoris in severe septic patients decreased with the prolongation of ICU stay, and there was no significant difference between the two groups at the first and third day of ICU admission. The muscle thickness of quadriceps femoris at different measuring positions in the survival group was significantly greater than those in the death group 7 days after admission to the ICU [M-QMLT D7 (cm): 0.50±0.26 vs. 0.39±0.19, T-QMLT D7 (cm): 0.58±0.29 vs. 0.45±0.21, both P < 0.05]. The atrophy rate of quadriceps femoris muscle thickness at different measuring positions 3 and 7 days after admission to ICU in the survival group was significantly lower than those in the death group [(D3-D1)/D1: (8.33±3.44)% vs. (9.74±3.91)%, (D7-D1)/D1: (12.21±4.76)% vs. (19.80±6.15)%, (TD3-TD1)/TD1: (7.83±4.26)% vs. (10.51±4.75)%, (TD7-TD1)/TD1: (11.10±5.46)% vs. (20.22±6.05)%, all P < 0.05]. Multivariate Logistic regression analysis showed that M-QMLT D7, T-QMLT D7, (D3-D1)/D1, (D7-D1)/D1, (TD3-TD1)/TD1, (TD7-TD1)/TD1 were independent risk factors for in-hospital mortality (all P < 0.05). The results were stable after adjusting for confounding factors. ROC curve analysis showed that (TD7-TD1)/TD1 [area under the ROC curve (AUC) was 0.853, 95% confidence interval (95% CI) was 0.773-0.934] was superior to (D7-D1)/D1, T-QMLT D7, M-QMLT D7, (TD3-TD1)/TD1 and (D3-D1)/D1 [AUC was 0.821 (0.725-0.917), 0.692 (0.582-0.802), 0.683 (0.573-0.794), 0.680 (0.569-0.791), 0.622 (0.502-0.742)]. Conclusions:For septic patients in ICU, bedside ultrasound monitoring of quadriceps femoris muscle thickness and atrophy rate has a certain predictive value for in-hospital mortality, and a certain guiding significance in clinical treatment and predicting the prognosis of sepsis.
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Objective:To investigate the correlations of β cell dedifferentiation in non-diabetic subjects with risk factors for type 2 diabetes mellitus(T2DM).Methods:Immunofluorescence staining with insulin and β cell dedifferentiated marker ALDH1A3 was used to evaluate the β cell dedifferentiation levels in 38 non-diabetic and 23 T2DM. Correlation analyses were performed between β cell dedifferentiation levels and available clinical parameters including age, body mass index, HbA 1C level, triglycerides, and cholesterol levels in non-diabetic subjects. Results:β cell dedifferentiation level defined by the positive expression of ALDH1A3 in β cells(ALDH1A3 + INS + cell proportion) was significantly elevated in T2DM subjects( P<0.001). In PreD subjects, ALDH1A3 + INS + cells proportion were decreased( P=0.050) and negatively correlated with HbA 1C( r=-0.44, P=0.006), but not with age and body mass index. The analysis of correlation with lipidemic parameters showed that ALDH1A3 + INS + cells proportion was positively correlated with plasma total cholesterol level( r=0.39, P=0.045), but not plasma total triglyceride. Conclusion:ALDH1A3 + INS + cells were found to be decreased in prediabetes, suggesting that there may be enhanced β-cell identity in prediabetes to compensate for insulin secretion requirements; ALDH1A3 + INS + cells were elevated in people with high plasma total cholesterol levels, suggesting that total cholesterol may be one of the factors that induce β-cell dedifferentiation.
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Epithelial-mesenchymal transition (EMT ) is known to be involved in airway remodeling and fibrosis of bronchial asthma. However, the molecular mechanisms leading to EMT have yet to be fully clarified. The current study was designed to reveal the potential mechanism of microRNA-21 (miR-21) and poly (ADP-ribose) polymerase-1 (PARP-1) affecting EMT through the PI3K/AKT signaling pathway. Human bronchial epithelial cells (16HBE cells) were transfected with miR-21 mimics/inhibitors and PARP-1 plasmid/small interfering RNA (siRNA). A dual luciferase reporter assay and biotin-labeled RNA pull-down experiments were conducted to verify the targeting relationship between miR-21 mimics and PARP-1. The migration ability of 16HBE cells was evaluated by Transwell assay. Quantitative real-time polymerase chain reaction and Western blotting experiments were applied to determine the expression of Snail, ZEB1, E-cadherin, N-cadherin, Vimentin, and PARP-1. The effects of the PI3K inhibitor LY294002 on the migration of 16HBE cells and EMT were investigated. Overexpression of miR-21 mimics induced migration and EMT of 16HBE cells, which was significantly inhibited by overexpression of PARP-1. Our findings showed that PARP-1 was a direct target of miR-21, and that miR-21 targeted PARP-1 to promote migration and EMT of 16HBE cells through the PI3K/AKT signaling pathway. Using LY294002 to block PI3K/AKT signaling pathway resulted in a significant reduction in the migration and EMT of 16HBE cells. These results suggest that miR-21 promotes EMT and migration of HBE cells by targeting PARP-1. Additionally, the PI3K/AKT signaling pathway might be involved in this mechanism, which could indicate its usefulness as a therapeutic target for asthma.