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Objective: To investigate the drug-resistant gene characteristics and core genome characteristics of carbapenem-resistant Enterobacter cloacae (CR-ECL) in rural residents of Weifang City, Shandong Province. Methods: Fecal samples were collected from rural community residents in Weifang City, Shandong Province in 2017. Drug-resistant strains were screened using a carbapenem-resistant enterobacter chromogenic medium. CR-ECL positive strains were acquired via Matrix Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry(MALDI-TOFMS) analysis. The antibiotic resistance phenotype of CR-ECL was determined using a microbroth dilution assay. Whole genome sequencing (WGS) and analysis were conducted, along with an examination of the immediate vicinity of the blaNDM gene and phylogenetic analysis of the strains. Results: A total of 628 fecal samples were collected and tested, of which 6 were CR-ECL positive (detection rate 0.96%), all exhibiting multiple drug resistance (MDR) phenotypes. Six CR-ECL strains had four MLST genotypes (ST), all of which carried multiple drug resistance genes (blaNDM-1, blaNDM-5, etc.) and virulence genes (acrA, acrB, entB, fepC, etc.). There were mobile genetic elements ISAba125, TN3-IS3000, TN3 and IS5 in the genetic environment surrounding the blaNDM gene. The phylogenetic tree showed that the multi-locus sequence typing of the core genome (cgMLST) was consistent with the single nucleotide polymorphism (SNPs) results. The cgMLST results showed that the allele differences between strains 2BC0101B and 2BC0251B, 2BG0561B and 2BI0221B were 2 and 1, respectively. The SNPs results showed that the above two pairs of bacteria also clustered together. It was found that the strains of chicken fecal samples in the National Center for Biotechnology Information (NCBI) database were located in the center of the evolutionary tree, and the local sequences could be traced back to American human sequences. Conclusion: Multidrug-resistant CR-ECL is detected in rural community residents in Weifang City, Shandong Province.
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Humanos , Antibacterianos/uso terapêutico , Enterobacter cloacae/genética , Tipagem de Sequências Multilocus , beta-Lactamases/genética , Filogenia , População Rural , Carbapenêmicos/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
Objective: To investigate the drug-resistant gene characteristics and core genome characteristics of carbapenem-resistant Enterobacter cloacae (CR-ECL) in rural residents of Weifang City, Shandong Province. Methods: Fecal samples were collected from rural community residents in Weifang City, Shandong Province in 2017. Drug-resistant strains were screened using a carbapenem-resistant enterobacter chromogenic medium. CR-ECL positive strains were acquired via Matrix Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry(MALDI-TOFMS) analysis. The antibiotic resistance phenotype of CR-ECL was determined using a microbroth dilution assay. Whole genome sequencing (WGS) and analysis were conducted, along with an examination of the immediate vicinity of the blaNDM gene and phylogenetic analysis of the strains. Results: A total of 628 fecal samples were collected and tested, of which 6 were CR-ECL positive (detection rate 0.96%), all exhibiting multiple drug resistance (MDR) phenotypes. Six CR-ECL strains had four MLST genotypes (ST), all of which carried multiple drug resistance genes (blaNDM-1, blaNDM-5, etc.) and virulence genes (acrA, acrB, entB, fepC, etc.). There were mobile genetic elements ISAba125, TN3-IS3000, TN3 and IS5 in the genetic environment surrounding the blaNDM gene. The phylogenetic tree showed that the multi-locus sequence typing of the core genome (cgMLST) was consistent with the single nucleotide polymorphism (SNPs) results. The cgMLST results showed that the allele differences between strains 2BC0101B and 2BC0251B, 2BG0561B and 2BI0221B were 2 and 1, respectively. The SNPs results showed that the above two pairs of bacteria also clustered together. It was found that the strains of chicken fecal samples in the National Center for Biotechnology Information (NCBI) database were located in the center of the evolutionary tree, and the local sequences could be traced back to American human sequences. Conclusion: Multidrug-resistant CR-ECL is detected in rural community residents in Weifang City, Shandong Province.
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Humanos , Antibacterianos/uso terapêutico , Enterobacter cloacae/genética , Tipagem de Sequências Multilocus , beta-Lactamases/genética , Filogenia , População Rural , Carbapenêmicos/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
Objective To explore the prognostic factor and its predictive value of patients with Wilson disease-related acute-on-chronic liver failure(WD-ACLF).Methods The clinical data of 70 patients diagnosed as WD-ACLF admitted to the Department of Encephalopathy of the First Affiliated Hospital of Anhui University of Chinese Medicine from January 1,2017 to January 1,2022 were retrospectively collected.According to the 12-week prognosis,patients were divided into survival group(n=36)and death group(n=34).The data of the two groups were analyzed by univariate and multivariate logistic analysis to screen the prognostic risk factors and evaluate their predictive value.The model coefficient is omnibus tested,and the model-fitting degree is evaluated by the Hosmer-Lemeshow test.ROC curve was used to analyze the prognostic value for WD-ACLF between the new model and chronic liver failure-sequential organ failure assessment(CLIF-SOFA)score,model for end-stage liver disease(MELD)score and Child-Turcotte-Pugh(CTP)score.Results A total of 70 WD-ACLF patients were enrolled in present study,including 36 cases in survival group[22 males and 14 females with median age of 30.0(17.3,40.0)]and 34 cases in death group[25 males and 9 females with median age of 34.0(28.8,41.0)].Univariate analysis showed that the course of disease,prothrombin time(PT),activated partial thromboplastin time(APTT)were shorter in survival group than that in death group,the white blood cells(WBC),international normalized ratio(INR),aspartate transaminase(AST),total bilirubin(TBIL),blood urea nitrogen(BUN),creatinine(Cre)and ceruloplasmin(CER)levels and the proportion of infection,ascites,and upper gastrointestinal bleeding were lower in survival group than those in death group,however,the proportion of infection,ascites and upper digestive bleeding in the survival group were lower than those in the death group.Meanwhile,the red blood cells(RBC),hemoglobin(Hb),Na+ and total cholesterol(TC)level in the survival group were higher than those in the death group(P<0.05 or P<0.01).The results of multivariate logistic regression analysis showed that disease course(OR=1.176,95%CI 1.043-1.325),INR(OR=7.635,95%CI 1.767-32.980),TBIL(OR=1.012,95%CI 1.003-1.021),and upper gastrointestinal bleeding(OR=11.654,95%CI 1.029-131.980)were independent risk factors affecting the prognosis of WD-ACLF(P<0.05).Based on the results of logistic regression analysis,a joint model for predicting the prognosis of WD-ACLF was established.The AUC of the model for evaluating the prognosis of WD-ACLF was 0.941,which was greater than the CLIF-SOFA score(AUC=0.802),MELD score(AUC=0.897),and CTP score(AUC=0.722).Conclusions The course of disease,TBIL,INR,and upper gastrointestinal bleeding are risk factors that affect the prognosis of WD-ACLF.The prognosis model established based on this can more accurately predict the prognosis of WD-ACLF patients,and its predictive value is superior to CLIF-SOFA score,MELD score,and CTP score.
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Objective To investigate the efficacy and safety of Tubridge flow diverter(TFD)in the treatment of ruptured intracranial aneurysms.Methods The clinical data of 13 patients with aneurysmal subarachnoid hemorrhage,who received TFD treatment at the First Affiliated Hospital of Zhengzhou University between March 2019 and Jul 2022,were retrospectively collected.The perioperative materials and follow-up results were summarized and analyzed.Results Successful operation was accomplished in all the 13 patients(13 aneurysms in total).TFD and coil embolization were simultaneously performed in 10 patients(simultaneous treatment),spring coil filling followed by selective staged TFD placement was adopted in 2 patients(staged treatment),and pure TFD placement was employed in one patient.The incidence of perioperative complications was 15.4%(2/13),including asymptomatic ischemic event in one patient and extra-ventricular drainage-related postoperative bleeding in another patient,which caused death of the patient.The median follow-up time was 6.5 months,and 83.3%of patients(10/12)completed cerebral angiography reexamination with DSA.OKM grade D(complete occlusion of the aneurysm)was obtained in 8 patients(80%),and OKM grade C(residual aneurysm neck)in 2 patients.Conclusion For ruptured intracranial aneurysms,TFD implantation is a clinically feasible treatment with favorable safety and efficacy.
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Objective:To explore therapeutic effect of sacubitril valsartan sodium combined with Wenxin granule in the treatment of hypertension complicated with paroxysmal atrial fibrillation(AF)and its effect on cardiac electro-physiological structure.Methods:A total of 116 patients with hypertension and paroxysmal atrial fibrillation treated in our hospital from Oct 2021 to Nov 2022 were consecutively selected.According to random number table,they were divided into Wenxin granule group(received Wenxin granule treatment based on routine antihypertensive ther-apy)and combined treatment group(received sacubitril valsartan sodium combined Wenxin granule therapy based on routine antihypertensive therapy)with 58 cases in each group,and both groups were consecutively treated for six months.Clinical symptom score,AF burden,P wave duration,P wave dispersion,left atrial diameter(LAD),left ventricular end-diastolic diameter(LVEDd)and left ventricular ejection fraction(LVEF)were compared between two groups before and after treatment.Results:After treatment,compared with Wenxin granule group,there were significant reductions in clinical symptom score[(1.66±0.69)scores vs.(1.40±0.53)scores],AF burden[4.43(1.65)%vs.1.62(3.50)%],P wave duration[(112.17±6.46)ms vs.(109.29±8.59)ms],P wave dispersion[(32.47±8.11)ms vs.(29.02±7.49)ms]and LAD[(34.83±3.41)mm vs.(33.40±3.74)mm]in combined treatment group(P<0.05 or<0.01).There were no significant difference in LVEDd and LVEF between two groups,P>0.05 both.Conclusion:Sacubitril valsartan sodium combined with Wenxin granule can significantly im-prove clinical symptoms and atrial fibrillation burden,reduce the susceptibility to atrial fibrillation,and inhibit atrial electrical remodeling and structural remodeling in patients with hypertension complicated with paroxysmal atrial fi-brillation.
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Objective To investigate the anti-inflammatory action of Celastrol in the ocular tissues of mice with ex-perimental autoimmune uveitis(EAU)and its effect on microglia polarization.Methods A total of 36 healthy B10.RⅢmice at 6-8 weeks of age were selected and randomly divided into the normal control group,EAU solvent control group and Celastrol intervention group,with 12 mice in each group.The interphotoreceptor retinoid-binding protein(IRBP)161-180 and Freund's complete adjuvant were mixed by thorough emulsification and injected subcutaneously into the bilateral thighs and tails of mice in the EAU solvent control group and the Celastrol intervention group with a total volume of 200 μL and 50 μg IRBP 161-180 in each mouse.On 7-14 days after immunization,mice in the Celastrol intervention group received a daily intraperitoneal injection of 0.5 mg·kg-1 Celastrol,and mice in the EAU solvent control group were injected with an equivalent dose of sterile Phosphate Buffered Saline solution.On the 14th day after immunization,the anterior segment of mice in each group was observed by slit-lamp microscope and Hematoxylin and Eosin(HE)staining of tissue sections was performed;the clinical and histopathological scores of mice in each group were obtained by reference to the Caspi grading standards;immunofluorescence staining was used to observe the activation of microglia in the eyes of mice;Western blot was used to detect the protein expression levels of inducible nitric oxide synthase(iNOS)and arginase-1(Argl)in the reti-na;quantitative real-time PCR was used to detect the relative mRNA expression of inflammatory factors in the retina,such as tumor necrosis factor(TNF)-α,interleukin(IL)-1β and IL-6.GraphPad Prism 9.0 was used for data analysis.Results On the 14th day after immunization,it was observed by the slit-lamp microscope that the anterior segment of mice in the EAU solvent control group was markedly congested with dilated iris blood vessels,corneal edema,and anterior chamber exudation;the inflammation in the anterior segment of mice in the Celastrol intervention group was markedly at-tenuated,and the iris blood vessels were seen to be mildly congested.Compared with the normal control group,the clini-cal scores of mice in the EAU solvent control group and the Celastrol intervention group were significantly elevated(both P<0.05);the clinical scores of mice in the Celastrol intervention group were lower than those in the EAU solvent control group(P<0.05).HE staining results showed that on the 14th day after immunization,mice in the EAU solvent control group showed severe retinal folds and detachment with diffuse infiltration of inflammatory cells,while mice in the Celastrol intervention group showed slight structural damage to the retina and a small amount of inflammatory cell infiltration.Com-pared with the normal control group,the histopathological scores of mice in the EAU solvent control group and the Celas-trol intervention group were significantly elevated(both P<0.05);the histopathological scores of mice in the Celastrol in-tervention group were lower than those in the EAU solvent control group(P<0.05).The intraocular Iba1+cell densities of mice in the normal control,EAU solvent control and Celastrol intervention groups were(1.00±0.12)%,(36.07± 4.57)%,and(1.83±0.36)%,respectively.Compared with the normal control group,the number of Iba1+cells in the eyes of mice in the EAU solvent control group and the Celastrol intervention group significantly increased(both P<0.05);compared with the EAU solvent control group,the number of Iba1+cells in the eyes of mice in the Celastrol intervention group was significantly reduced(P<0.05).Compared with the normal control group,the expression levels of iNOS and Arg1 proteins in the retinas of mice in the EAU solvent control group were significantly elevated(both P<0.01);compared with the EAU solvent control group,the expression of iNOS protein in the retinas of mice in the Celastrol intervention group was significantly reduced(P<0.01).Compared with the normal control group,the relative mRNA expressions of TNF-α.IL-1β,and IL-6 in the retinas of mice in the EAU solvent control group was significantly elevated(all P<0.05);compared with the EAU solvent control group,the relative mRNA expressions of TNF-α,IL-1 β,and IL-6 in the retinas of mice in the Celastrol intervention group significantly decreased(all P<0.05).Conclusion Celastrol inhibits Ml microglia activation and reduces the production of retinal inflammatory factors TNF-α,IL-1 β and IL-6 in EAU mice,thereby attenuating the in-flammatory reaction.
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Objective:To investigate the quality control of magnetic resonance enterography(MRE)in the diagnosis of intestine diseases,and analyze the factors that affected the imaging quality of MRE,and enhance the imaging quality of MRE through adopted the measures of quality control.Methods:The documents of MRE examinations of 167 patients with intestinal disease who admitted to the 900th Hospital of People's Liberation Army Joint Service Support Force from May 2018 to March 2023 were retrospectively analyzed.The image qualities of all patients were evaluated after they completed clinical and image examinations.The reasons that image quality could not meet the requirement of diagnosis were analyzed.And then,the measures of quality control were proposed.Results:In 167 patients with intestinal disease,the MRE images of 153 patients(91.62%)could meet the requirement of diagnosis.In 14 patients(8.38%)whose MRE images could not meet the requirement of diagnosis,the reason of 3 cases(1.80%)was poor respiratory coordination,and that of 2 cases(1.20%)was there were more severe magnetic sensitive artifacts in images,and that of 1 case(0.60%)was severe intestinal peristalsis leaded to blurred images,and that of 2 cases(1.20%)was the flow void effect from intestinal peristalsis inside of intestinal cavity could not meet the requirement of diagnosis,and that of 4 cases(2.40%)was the intestinal tube without incomplete dilation caused by poor oral filling contrast agent,and that of 2 cases(1.20%)was many residues in intestine due to poor preparation for intestine.Aimed at the factors that MRE images could not meet requirement of diagnosis,we proposed the following quality control measures:①the biphasic contrast agents with favorable safety,without severe adverse reactions,which can fully dilate intestinal cavity,should be selected.②we should do well for the dilation of intestinal tube,and inhibit the intestinal peristalsis and conduct respiratory training.③we should conduct scan with wide field at coronal site,so as to display panorama image of intestine.④The scans of conventionally anatomical sequence and functional imaging sequence on axis position were performed on lesions.Conclusion:MRE technique should choose appropriate contrast agent in the quality control of the diagnosis of intestine diseases,and do well the preparation for patients before examination.Using intraluminal contrast agents,conducting intestinal dilation and optimal imaging technique are essential for obtaining intestinal MRE images with high quality.
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AIM To establish a quantitative analysis of multi-components by single-marker(QAMS)method for the simultaneous content determination of gastrodin,parishin E,syringin,parishin B,parishin C,ferulic acid,parishin A,buddleoside,harpagoside and cinnamic acid in Tianma Toufengling Capsules.METHODS The analysis was performed on a 30℃thermostatic GL Science InertsilTM ODS-3 column(150 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 220,280 nm.Syringin was used as an internal standard to calculate the relative correction factors of the other nine constituents,after which the content determination was made.RESULTS Ten constituents showed good linear relationships within their own ranges(r≥0.999 7),whose average recoveries were 98.53%-102.22%with the RSDs of 1.26%-2.68%.The result obtained by QAMS approximated those obtained by external standard method.CONCLUSION This accurate and specific method can be used for the quality control of Tianma Toufengling Capsules.
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Objective To investigate the safety and effectiveness of transumbilical repair for hernia of linea alba within 3 cm above the umbilicus.Methods Clinical data of 26 patients who underwent transumbilical approach hernia repair in our hospital from June 2016 to July 2022 were retrospectively analyzed.Color ultrasound examination showed that the distance from the lower edge of the hernia to the upper edge of the umbilicus was≤3 cm.The hernia repair was performed through the fascial space via the upper edge approach of the umbilical ring.There were 7 boys and 19 girls.The age was 7 months to 11 years old(median,3 years old).The distance from the lower edge of the hernia sac to the upper edge of the umbilicus was(1.46±0.66)cm,and the diameter of the hernia of linea alba was(1.16±0.57)cm.Results The surgery was completed smoothly.The operation time was(39.1±26.3)min.No complication was noted.All the patients were discharged one day after surgery.The follow-ups lasted for 1 year and 2 months to 7 years and 3 months(median,5 years and 1 month).No wound infection,bleeding or other complications occurred.No recurrence of hernia or formation of skin granulomas happened.Conclusion Transumbilical approach repair for hernia of linea alba within 3 cm above the umbilicus is safe and effective,with good cosmetic results.
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Objective:To summarize the imaging features of severe unilateral transverse sinus and sigmoid sinus thromboses, and evaluate the efficacy and safety of intravascular interventional therapy in them.Methods:Thirty-seven patients with severe unilateral transverse sinus and sigmoid sinus thromboses clinically mainly manifested as intracranial hypertension and accepted endovascular intervention in Department of Interventional Radiology, First Affiliated Hospital of Zhengzhou University from June 2012 to September 2022 were chosen; their clinical data were retrospectively analyzed and imaging features were summarized. Short-term efficacy was evaluated according to blood flow restoration degrees and pressure gradient reduction in the occlusive sinus and modified neurological symptoms before and after endovascular intervention. Hospitalized complications were observed; safety and long-term efficacy were evaluated according to postoperative clinical follow-up and imaging results 6-12 months after endovascular intervention.Results:(1) Preoperative brain MRI and (or) CT showed different degrees of swelling of the brain tissues, with the affected side as the target; mixed signals/density shadow could be seen in the blocked transverse sinus and sigmoid sinus; venous cerebral infarction or post-infarction cerebral hemorrhage could be combined in some patients. MRV, CTV and DSA showed poor or completely occluded transverse sinus and sigmoid sinus while normal in the contralateral side; obvious thrombus filling-defect was observed in the occluded venous sinus after mechanical thrombolysis. (2) Occlusive sinus blood flow was restored in all patients after endovascular intervention, and pressure gradient of the occlusive segment decreased from (16.6±3.3) mmHg before to (2.8±0.8) mmHg after endovascular intervention. Before discharge, clinical symptoms of all patients were significantly improved (modified Rankin scale [mRS] scores of 0 in 30 patients, 1 in 5 patients, 2 in 1 patient and 3 in 1 patient), and 2 patients had unilateral limb movement disorder (muscle strength grading III and IV, respectively). All patients received clinical follow-up for (9.6±3.0) months. At the last follow-up, neurological function obviously improved compared with that before endovascular intervention, without new neurosystem-related symptoms (mRS scores of 0 in 30 patients, 1 in 6, and 2 in 1 patient). In 34 patients received MRV or DSA follow-up, 28 had complete recanalization of occlusive sinus and 6 had partial recanalization, without obvious stenosis or recurrent occlusion.Conclusions:Severe unilateral transverse sinus and sigmoid sinus thrombosis can cause local intracranial venous blood stasis, and then cause "increased regional venous sinus pressure", which is manifested as unilateral brain tissue swelling and even venous cerebral infarction or post-infarction cerebral hemorrhage. Early diagnosis and endovascular intervention can obviously improve the prognosis of these patients, enjoying good safety.
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Polycystin-2 (also known as PC2, TRPP2, PKD2) is a major contributor to the underlying etiology of autosomal dominant polycystic kidney disease (ADPKD), which is the most prevalent monogenic kidney disease in the world. As a transient receptor potential (TRP) channel protein, PC2 exhibits cation-permeable, Ca2+-dependent channel properties, and plays a crucial role in maintaining normal Ca2+ signaling in systemic physiology, particularly in ADPKD chronic kidney disease. Structurally, PC2 protein consists of six transmembrane structural domains (S1-S6), a polycystin-specific “tetragonal opening for polycystins” (TOP) domain located between the S1 and S2 transmembrane structures, and cytoplasmic N- and C-termini. Although the cytoplasmic N-terminus and C-terminus of PC2 may not be significant in the gating of PC2 channels, there is still much protein structural information that needs to be thoroughly investigated, including the regulation of channel function and the assembly of homotetrameric ion channels. This is further supported by the presence of human disease-associated mutation sites on the PC2 structure. Moreover, PC2 synthesized in the endoplasmic reticulum is enriched in specific subcellular localization via membrane transport and can assemble itself into homotetrameric ion channels, as well as form heterotrimeric receptor-ion channel complexes with other proteins. These complexes are involved in a wide range of physiological functions, including the regulation of mechanosensation, cell polarity, cell proliferation, and apoptosis. In particular, PC2 assembles with chaperone proteins to form polycystic protein complexes that affect Ca2+ transport in cell membranes, cilia, endoplasmic reticulum, and mitochondria, and are involved in activating cell fate-related signaling pathways, particularly cell differentiation, proliferation, survival, and apoptosis, and more recently, autophagy. This leads to a shift of cystic cells from a normal uptake, quiescent state to a pathologically secreted, proliferative state. In conclusion, the complex structural and functional roles of PC2 highlight its critical importance in the pathogenesis of ADPKD, making it a promising target for therapeutic intervention.
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In this study, fluvoxamine maleate sustained-release pellet system tablets were prepared and were used to evaluate their release behaviors in vitro. Fluvoxamine maleate pellets were prepared using centrifugal-spherization method and coated by fluidized bed as bottom-spray. The multi-unit sustained-release pellets and appropriate excipients for prescription volumes were mixed uniformly and then compressed to tablets. Screening and determining the optimal formulation of drug loaded pellets through L8 (24) Taguchi experiment. Using Minitab software to design a DOE experiment with 24 partial factors, including material temperature, fan speed, atomization pressure, and spray rate to optimize the bottom spray coating process. Taking monostearate glycerol ester with a particle size of 24-40 mesh as the main diluent for tableting to relieve the delamination phenomenon between pellets and excipients during tablet pressing and reduce mechanical damage to the coating film. By examining the powder fluidity indexes such as angle of repose, bulk density, tapped density, and Hausner ratio of mixed particles, it was found that the flowability and compressibility are good and suitable for direct compression. Evaluate the basic properties of the sustained-release tablets, investigate the in vitro release behavior and study the release mechanism. The results of in vitro release test showed that the self-made sustained-release tablets could disintegrate into independent pellet units in phosphate buffer at pH 6.8 and release slowly within 24 h, which conformed to the first-order drug release model. The fluvoxamine maleate sustained-release pellet system tablets meet the requirements of preparation design and has a great commercial prospect.
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Cancer is one of the deadliest diseases affecting the health of human beings. With limited therapeutic options available, complementary and alternative medicine has been widely adopted in cancer management and is increasingly becoming accepted by both patients and healthcare workers alike. Chinese medicine characterized by its unique diagnostic and treatment system is the most widely applied complementary and alternative medicine. It emphasizes symptoms and ZHENG (syndrome)-based treatment combined with contemporary disease diagnosis and further stratifies patients into individualized medicine subgroups. As a representative cancer with the highest degree of malignancy, pancreatic cancer is traditionally classified into the "amassment and accumulation". Emerging perspectives define the core pathogenesis of pancreatic cancer as "dampness-heat" and the respective treatment "clearing heat and resolving dampness" has been demonstrated to prolong survival in pancreatic cancer patients, as has been observed in many other cancers. This clinical advantage encourages an exploration of the essence of dampness-heat ZHENG (DHZ) in cancer and investigation into underlying mechanisms of action of herbal formulations against dampness-heat. However, at present, there is a lack of understanding of the molecular characteristics of DHZ in cancer and no standardized and widely accepted animal model to study this core syndrome in vivo. The shortage of animal models limits the ability to uncover the antitumor mechanisms of herbal medicines and to assess the safety profile of the natural products derived from them. This review summarizes the current research on DHZ in cancer in terms of the clinical aspects, molecular landscape, and animal models. This study aims to provide comprehensive insight that can be used for the establishment of a future standardized ZHENG-based cancer animal model.
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Animais , Humanos , Medicina Tradicional Chinesa , Temperatura Alta , Neoplasias Pancreáticas/terapia , Modelos Animais , SíndromeRESUMO
Objective To investigate the clinical and imaging features of testicular interstitial lesions in children.Methods The clinical and imaging data of 8 children with testicular interstitial lesions confirmed by pathology were analyzed retrospectively.Results There were 8 cases of precocious puberty,5 cases of elevated sex hormones,and 2 cases of congenital adrenal hyperplasia(CAH).The lesions were located in the unilateral testis in 6 cases,bilateral in 2 cases,single in 4 cases,and multiple in 4 cases,with diameters 3-14 mm,all of them with clear boundaries.4 cases of leydig cell hyperplasia(LCH)showed heterogeneous hypoechoic lesions,with slightly significant blood flow signal on color Doppler flow imaging(CDFI);CT showed iso-density lesions with mild enhanced after enhancement;MRI showed iso-signal on T1WI,and T2WI fat suppression were iso-signal mainly with mild enhanced after enhancement.2 cases of leydig cell tumor(LCT)showed heterogeneous hypoechoic lesions with significant blood flow signals inside and around on CDFI,CT showed iso and slightly low density with low-density necrosis,which were inhomogeneously and significantly enhanced after enhancement.2 cases of testicular adrenal rest tumor(TART)showed heterogeneous hypoechoic lesions with significant blood flow signals inside and around on CDFI;CT showed iso and slightly low density,with inhomogeneouly and significantly enhanced after enhancement;MRI showed iso-signal mainly on T1WI,and T2WI fat suppression were slightly low signal mainly with mixed signal,which were inhomogeneously and significantly enhanced after enhancement,complicated with adrenal hyperplasia.Conclusion The imaging findings of testicular interstitial lesions in children have certain characteristics,and the combination of clinical manifestations,basic diseases,laboratory and a variety of imaging examinations are helpful in improving diagnostic efficiency.
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Objective:To investigate the correlation between cytokeratin 19 fragment(CYFRA21-1), modified ultrasound B-line and connective tissue disease associated with interstitial lung disease (CTD-ILD).Methods:The data of 112 patients with CTD hospitalized in the Department of Rheumatology and Immunology of the Second Hospital of Fujian Medical University from September 2019 to December 2021 were retrospectively collected. Sixty patients in the CTD-ILD group and 52 patients in the connective tissue disease without interstitial lung disease (CTD-noILD) group were included. The t-test and χ2 test were used to compare the demographic characteristics and tumor-associated antigens of the two groups of patients. Modified ultrasound score and HRCT Warrick score were evaluated by Pearson correlation analysis. In addition, the relationship between CYFRA21-1, modified ultrasound score and Warrick score were evaluated, and the diagnostic efficacy of CYFRA21-1 and modified ultrasound of CTD-ILD was evaluated and analyzed by binary logistic regression analysis. Results:Patients in the CTD-ILD group had higher CYFRA21-1 concentrations than the CTD-no-ILD group[5.74(4.25, 9.79) ng/ml vs. 2.79(2.21, 3.23) ng/ml, Z=45.94, P<0.001], patients in the CTD-ILD group had higher modified ultrasound scores than the CTD-no-ILD group [44.5(36.5, 60.0) vs. 5.0 (3.2, 6.8), P<0.001]. Modified ultrasound score was positively correlated with Warrick score ( r=0.93, P<0.001) and CYRFA21-1 was positively correlated with modified ultrasound score ( r=0.39, P=0.042). The sensitivity of CYFRA21-1 in determining CTD-ILD was 81.7% and the specificity was 92.3% [ AUC (95% CI)=0.88(0.81, 0.95), P<0.001], the sensitivity of modified ultrasound B-line to determine CTD-ILD was 96.4% and the specificity was 92.9% [ AUC (95% CI)=0.99 (0.97, 1.00), P<0.001]. History of smoking[ OR(95% CI)=9.26(1.11, 77.12), P=0.040] and elevated CYFRA21-1 concentration[ OR(95% CI)=19.40(4.89, 76.95), P<0.001] were risk factors for CTD-ILD. Conclusion:CYFRA21-1 is expected to be a serum marker indicating concomitant ILD in patients with CTD. Modified ultrasound B-line to determine concomitant ILD in CTD patients has good diagnostic utility and can reflect the severity of pulmonary fibrosis in CTD-ILD patients.
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Objective:To investigate the clinical efficacy of humidified high flow nasal cannula oxygen inhalation (HFNC) versus conventional nasal cannula oxygen inhalation on hypoxemia after complex ventral hernia surgery in elderly patients.Methods:The retrospective cohort study was conducted. The clinical data of 80 elderly patients with hypoxemia after complex ventral hernia surgery who were admitted to Huadong Hospital Affiliated to Fudan University from January 2021 to June 2022 were collected. There were 44 males and 36 females, aged (74±7)years. Of the 80 patients, 40 cases undergoing HFNC were allocated into HFNC group, and 40 cases undergoing conventional nasal cannula oxygen inhalation were allocated into conventional group, respectively. Observation indicators: (1) postoperative blood gas analysis; (2) postoperative complications. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the rank sum test. Count data were represented as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Repeated measurement data were analyzed using the repeated ANOVA. Results:(1) Postoperative blood gas analysis. Before surgery and at 12 hours, 24 hours, 3 days after surgery, the partial pressure of blood oxygen was (13.5±2.3)kPa, (13.4±3.2)kPa, (13.8±2.3)kPa, (13.7±2.0)kPa for the HFNC group, and (12.7±2.1)kPa, (12.9±2.4)kPa, (12.3±2.5)kPa, (13.9±2.1) kPa for the conventional group. The partial pressure of carbon dioxide was (5.6±0.7)kPa, (5.0±0.6)kPa, (4.7±0.6)kPa, (4.9±0.6)kPa for the HFNC group, and (5.6±0.6)kPa, (4.4±0.8)kPa, (5.0±4.8)kPa, (5.1±1.1)kPa for the conventional group. The saturation of blood oxygen was 97.8%±2.2%, 98.1%±2.1%, 98.9%±1.8%, 99.2%±2.0% for the HFNC group, and 97.8%±3.1%, 97.8%±2.1%, 99.0%±1.5%, 98.8%±2.0% for the conventional group. The oxygenation index was 259±28, 300±45, 352±46, 353±57 for the HFNC group, and 262±29, 297±54, 304±63, 345±53 for the conventional group, respectively. There was a significant difference in the interven-tion effect of partial pressure of blood oxygen between the two groups ( Fgroup=4.09, P<0.05) and no significant difference in the time effect or interaction effect ( Ftime=2.37, Finteraction=1.71, P>0.05). There were significant differences in the time effect and interaction effect of partial pressure of carbon dioxide between the two groups ( Ftime=7.23, Finteraction=13.21, P<0.05) and no significant difference in the intervention effect ( Fgroup=1.02, P>0.05). There was a significant difference in the time effect of saturation of blood oxygen between the two groups ( Ftime=5.54, P<0.05) and no significant difference in the intervention effect or interaction effect ( Fgroup=1.78, Finteraction=0.46, P>0.05). There were signifi-cant differences in the intervention effect, time effect, interaction effect of oxygenation index between the two groups ( Fgroup=8.21, Ftime=42.07, Finteraction=3.49, P<0.05). (2) Postoperative complications. The time in intensive care unit and cases with pulmonary infection were 3(3,3)days and 3 for the HFNC group, versus 6(5,7)days and 10 for the conventional group, showing significant differences between the two groups ( Z=27.50, χ2=4.50, P<0.05). Cases with atelectasis and endotrachead intubation were 0 and 1 for the HFNC group, versus 4 and 7 for the conventional group, showing no significant difference between the two groups ( P>0.05). There was no death in either group. Conclusion:Humidified high flow oxygen inhalation has certain advantages over conventional nasal cannula oxygen inhalation in improving partial pressure of blood oxygen and oxygenation index after complex ventral hernia surgery in elderly patients.
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Objective:To investigate the risk factors related to successful endovascular recanalization for non-acute long segmental occlusion of internal carotid artery and propose a strategy for selecting proper candidates for such procedure.Methods:From January 2018 to October 2022, 120 consecutive patients with non-acute long segmental internal carotid artery occlusion received the first intended endovascular recanalization treatment in the First Affiliated Hospital of Zhengzhou University. Potential variables including epidemiology, symptomatology, angiographic morphology and interventional techniques were retrospectively analyzed. Univariate and multivariate logistic regression analyses were made to investigate the independent risk factors for successful recanalization. Four types were divided according to the existence of tapered stump and ophthalmic artery flow reversion based on DSA images: A: tapered stump (-), ophthalmic artery flow reversion (-); B: tapered stump (-), ophthalmic artery flow reversion (+); C: tapered stump (+), ophthalmic artery reversion (-); D: tapered stump (+), ophthalmic artery (+). Investigation of the relationship between procedure success rate and group dividing was performed.Results:Totally 120 patients were all included. The technical success rate was 75.83% (91/120). The periprocedural complication rate was 9.17% (11/120), including 4 (3.33%) intracranial hemorrhagic events, 1 (0.83%) ischemic stroke event, 1 (0.83%) microcatheter perforation, 3 (2.75%) cavernous carotid fistulas, 2 (1.67%) iatrogenic dissections. None of these complications led to severe neurological damage or death. Through multivariate logistic regression, tapered stump (OR=4.10, 95%CI 1.19-14.16), retrograde filling of ophthalmic artery (OR=3.16, 95%CI 1.13-8.88), only cervical segment occlusion of internal carotid artery (OR=10.78, 95%CI 2.08-55.74) were the independent risk factors associated with higher technical success rate. All cases were divided into A-D four types considering the tapered stump and reversed ophthalmic flow existing or not. Technical success rates in A-D types were 30.00% (3/10), 66.67% (8/12), 70.00% (28/40), 89.66% (52/58) respectively, and the complication rates of the four types were 10.00% (1/10), 8.33% (1/12), 17.50% (7/40), 3.45% (2/58). Multivariate logistic regression showed group pattern was the independent factor on technical success rate (OR=3.72, 95%CI 1.42-9.77).Conclusions:Tapered stump, reversed ophthalmic artery flow and pure extracranial artery occlusion are the independent factors for technical success rate. Group pattern which covered the tapered stump and reversed ophthalmic artery flow is also related to technical success rate. However, the results need further confirmation with the prospective trial and a larger sample.
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Objective:To investigate whether T-cadherin affects the radiotherapy sensitivity of endometrial cancer cells by regulating the Caspase-1 mediated pyrolysis pathway.Methods:Endometrial cancer and adjacent tissue samples were surgically obtained from 82 patients admitted to Hainan Western Central Hospital from October 2019 to March 2021. Immunohistochemical staining and qRT-PCR were used to detect the expression of T-cadherin in endometrial cancer and adjacent tissue samples. By transfecting pcDNA3.1-T-cadherin lentivirus to human endometrial cancer cell line Ishikawa, a stable Ishikawa cell line with high T-cadherin expression was established. Ishikawa cells were treated with 2 Gy X-ray, and the cell proliferation activity was detected after 24, 48, 72 h of culture. The cells were divided into the control group (normally cultured Ishikawa cells), irradiation group (treated with 2 Gy X-ray irradiation), pcDNA3.1-NC+irradiation group (transfected with pcDNA3.1-NC followed by 2 Gy X-ray irradiation), pcDNA3.1-T-cadherin+irradiation group (transfected with pcDNA3.1-T-cadherin followed by 2 Gy X-ray irradiation), pcDNA3.1-T-cadherin+VA765+irradiation group (transfected with pcDNA3.1-T-cadherin, plus 10 μmol/L VA765 treatment followed by 2 Gy X-ray irradiation). After corresponding treatment, cell survival rate was detected by CCK-8 assay. Cell proliferation was determined by colony formation assay. The level of lactate dehydrogenase (LDH) release was measured by LDH release test. The expression levels of Caspase-1, interleukin (IL)-1β, IL-18 and gasdermin A (GSDMA) were detected by Western blot. The expression level of Caspase-1 was detected by immunofluorescence staining. SPSS 23.0 statistical software was used for data analysis. One-way ANOVA was used for data comparison among multiple groups. LSD- t test was used for two-paired comparison. Results:The positive expression rate of T-cadherin protein in endometrial cancer tissues was 6.09%, lower than 87.80% in adjacent normal tissues ( t=58.48, P<0.01). The relative expression level of T-cadherin mRNA in endometrial cancer tissues was 1.00±0.07, significantly lower than 4.02±0.38 in adjacent normal tissues ( t=32.35, P<0.01). The cell activity of pcDNA3.1-T-cadherin++irradiation group was decreased, the number of cell clones was decreased, LDH release level was increased, the relative expression levels of Caspase-1, IL-1β, IL-18 and GSDMA proteins in cells were up-regulated, and red fluorescence intensity of Caspase-1 protein was enhanced ( P<0.01). However, the cell activity of pcDNA3.1-T-cadherin+VA765+irradiation group was increased, LDH release level was decreased, the relative expression levels of Caspase-1, IL-1β, IL-18 and GSDMA proteins were down-regulated, and the red fluorescence intensity of Caspase-1 protein was also decreased (all P<0.01). Conclusion:T-cadherin can increase the radiotherapy sensitivity of endometrial cancer cells by increasing Caspase-1 mediated pyrolysis.
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β-Klotho (KLB) is a member of the Klotho protein family, which is mainly distributed in organs and tissues such as the liver, fat, pancreas, and brain. KLB is a single-pass transmembrane protein whose structural characteristics determine that KLB acts as a co-receptor for fibroblast growth factor (FGF) 19/21 targeting the activation of fibroblast growth factor receptor (FGFRs). KLB is involved in the regulation of blood glucose, lipids, body weight, bile acid circulation, and hepatocyte proliferation in the FGF21/19-KLB-FGFRs pathway. This paperwill review the structural characteristics and distribution of KLB, as well as the regulatory mechanism of material energy and its role in tumor formation in the FGF19/21-KLB-FGFRs pathways.
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Traditional Chinese medicine(TCM) formula granules are highly praised for the advanced, convenient, and modern use of Chinese medicinal materials. The safety of TCM formula granules has long been a concern of regulatory authorities and the medical industry. A multi-center, prospective, open, non-interventional, and centralized monitoring was carried out for the patients treated with TCM formula granules in 252 medical institutions from February 5, 2020 to April 19, 2022. All the case data and the incidence of adverse drug reactions/events were recorded. This study evaluated the safety of TCM formula granules, aiming to provide a reference for the clinically use. A total of 20 547 patients were included in this study. Four adverse events were recorded, including 3 adverse drug reactions with an adverse drug reaction rate of 0.015%, all of which occurred in the digestive system. There was no serious adverse event, and no factors related to adverse drug reactions/events were identified. The incidence of adverse drug reactions/events associated with China Resources Sanjiu Medical & Pharmaceutical Co., Ltd. TCM formula granules was rare, which proved their safety in clinical use. A comprehensive data mining and objective analysis was carried out for the medicines with high frequency in TCM formula granules, the commonly used medicine pairs and combinations, and departmental medication. The drug use characteristics, prescription rules, and departmental use of TCM formula granules were summarized, which can shed light on the prescription compatibility and clinical application.