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Neoadjuvant therapy is a preoperative systemic treatment for patients with breast cancer. This therapy has greatly improved the clinical outcomes of human epidermal growth factor receptor 2 (HER2)-positive breast cancer, which is associated with poor prognosis. Currently, dual anti-HER2 antibodies, including trastuzumab and pertuzumab, combined with non-anthracycline chemotherapy is one of the standard regimens to achieve high pathologic complete response rate and satisfactory efficacy. The combination of trastuzumab with tyrosine kinase inhibitors, antibody-drug conjugate drugs, or immunotherapy combined with target therapy, under the indications of reasonable biomarkers, is effective for HER2-positive breast cancer. In this article, we briefly reviewed neoadjuvant therapy in the dual-targeting therapy era and discussed its future perspectives.
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AIM:To measure the superficial capillary plexus(SCP)vessel density(VD), deep capillary plexus(DCP)VD, and the area, circumference, and roundness index of the foveal avascular zone(FAZ)in healthy individuals of four ethnic groups, namely, Uyghur, Han, Kazakh, and Hui by optical coherence tomography angiography(OCTA), and to investigate the differences of blood flow parameters in macular area of healthy individuals among different ethnic groups in China.METHODS: A total of 80 cases(80 eyes)of healthy subjects if each of the four ethnic groups who went to the Eye Center of the Friendship Hospital of Ili Kazak autonomous Prefecture from December 2022 to March 2023 and met the criteria were selected for the study, with 320 eyes totally. The patients were grouped and numbered according to their ethnicity, and the spherical equivalent and axial length were obtained by using an autorefractor and IOL Master. The blood flow images of the macular area in the range of 3 mm×3 mm were obtained by using a DRI Triton OCT detector, and the images were analyzed by using the built-in IMAGENET6 software to obtain the blood flow parameters. Furthermore, the differences in the blood flow parameters between different ethnic groups as well as the effects of gender, age, and axial length on macular blood flow parameters of different ethnic groups were compared.RESULTS:There were no statistically significant differences in gender, age, axial length, diopter, and image quality(IQ)among the four groups of subjects(all P>0.05). Ethnic differences: in SCP, Uyghur inferior VD is higher than Kazakh, Hui inferior VD is higher than Han and Kazakh, Han and Hui nasal VD is higher than Uyghur, Kazakh foveal VD is higher than Han and Hui, Kazakh FAZ area is smaller than the other 3 ethnic groups, Han and Hui FAZ perimeter is larger than Kazakh, and Hui FAZ circularity index is lower than the other 3 ethnic groups; in DCP, Uyghur foveal VD is higher than Han and Hui, Kazakh foveal VD is higher than Han and Hui, Kazakh FAZ area and perimeter are smaller than the other 3 ethnic groups and Kazakh FAZ circularity index is higher than the other 3 ethnic groups(all P<0.05). Sex differences: in SCP, FAZ area and perimeter of Han females were larger than those of males, and FAZ circularity index of Hui females was higher than that of males(all P<0.05); in DCP, parafoveal VD and whole VD in females of all four ethnic groups were higher than those of males(all P<0.05). Age correlation: in SCP, age was negatively correlated with the FAZ circularity index of Kazakh; in DCP, age was negatively correlated with the parafoveal and the whole VD of Han, Kazakh, and Hui(all P<0.05). Axial length correlation: in SCP, the axial length was negatively correlated with Kazakh and Hui foveal VD, Hui parafoveal VD, Uyghur, Kazakh and Hui whole VD, and positively correlated with Kazakh FAZ area and perimeter; in DCP, the axial length was negatively correlated with Uyghur, Kazakh, Hui foveal VD, Hui whole VD, and positively correlated with Kazakh and Hui FAZ area and perimeter(all P<0.05).CONCLUSION:There were differences in macular blood flow parameters among the Uyghur, Han, Kazakh, and Hui populations, with the area and perimeter of the FAZ of the Kazakh significantly smaller than those of the other three ethnic groups. Gender, age, and axial length are also related to macular blood flow parameters.
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Objective:To study the molecular phylogeny and virulence gene profile of Francisella salimarina. Methods:Phylogenetic analysis of Francisella salimarina was performed based on the global genome data of related Francisella species on GenBank database. The consistency in phylogenetic analysis based on single marker genes (such as 16S rRNA gene, rpoB gene and mdh gene) and the core genome as compared. Virulence genes and antibiotic resistance genes were annotated using the virulence factor database (VFDB) and the Comprehensive Antibiotic Resistance Database (CARD), respectively. The virulence of Francisella salimarina was analyzed with a Galleria mellonella (greater wax moth) infection model using Francisella philomiragia ATCC 25015 T as reference strain. Results:The phylogenetic analysis revealed that Francisella salimarina was closely related to Francisella philomiragia. The phylogenetic tree based on mdh gene was highly similar to that based on the core genome. Francisella salimarina could be differentiated from other related species by 16S rRNA gene or mdh gene, with the latter being more accurate. Eight Francisella salimarina strains carried multiple virulence genes, mainly involved in secretion, adhesion, immune regulation, motility and stress survival. Moreover, beta-lactam resistance gene blaFPH was identified in all eight strains. Francisella salimarina showed high lethality in the Galleria mellonella infection model, which was similar to Francisella philomiragia ATCC 25015 T. Conclusions:Francisella salimarina was a rare pathogen with similar pathogenicity to Francisella philomiragia. The mdh gene could be used as a molecular target for rapid identification of Francisella salimarina.
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Objective:To identify and characterize two Balneatrix alpica strains isolated from a patient′s blood sample (strain X117) and the natural hot spring water in the patient′s residential district (strain GN-1), and to provide experimental evidence for the pathogenic diagnosis of clinical infection caused by this rare pathogen. Methods:Biochemical phenotypic identification, matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), 16S rRNA gene sequencing, phylogenetic analysis, single-nucleotide polymorphism (SNP) analysis, and genome-wide analysis were performed to accurately determine the taxonomic status of the isolates X117 and GN-1 by using Balneatrix alpica DSM 16621 T as a reference. Microdilution broth method was used to test their antimicrobial susceptibility. The virulence genes carried by them were annotated and analyzed using the virulence factor database (VFDB). Results:Strains X117 and GN-1 formed light yellow or tan colonies with mottled surfaces on Columbia blood agar and chocolate agar plates after 4 d of culture. They were Gram-negative rods and positive for oxidase and indole tests, which were consistent with the characteristics of Balneatrix alpica DSM 16621 T. The phylogenetic analysis based on the 16S rRNA gene showed that the isolates X117 and GN-1 were both Balneatrix alpaca. The average nucleotide identity (ANI) values between the two isolates and Balneatrix alpica DSM 16621 T were 98.44% and 98.41%, respectively, and the digital DNA-DNA hybridization (dDDH) values were both 87.1%. The SNP distance between the two strains was 13, indicating that X117 and GN-1 might belong to the same clone. The antibiotic susceptibility testing showed that all of the three Balneatrix alpica strains were sensitive to the commonly used antibiotics against Gram-negative rods. The virulence genes carried by the three Balneatrix alpica strains were mainly involved in adhesion, invasion, flagella and biofilm formation. Conclusions:This study identified a case of bloodstream infection caused by Balneatrix alpica which was closely related to natural hot spring water. Natural hot spring water migh be an important source of clinical infections caused by this species.
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Objective:To identify and characterize one Spiroplasma strain (designated as DGKH1) isolated from the blood of a patient with sepsis. Methods:The traditional bacterial culture, staining, morphological observation, physiological and biochemical identification, 16S rRNA gene sequencing, phylogenetic analysis, genome sequencing, and the genome-related index analysis were performed to accurately determine the taxonomic status of the strain DGKH1. Antibiotic susceptibility testing was performed using a specific kit for culturing and testing Ureaplasma urealyticum/ Metamycoplasma hominis. Results:The strain DGKH1 could weakly grow on Columbia blood agar, chocolate agar, and Haemophilus chocolate 2 agar. However, it did not grow in liquid culture medium containing tetracycline (4 μg/ml), doxycycline (1 μg/ml), minocycline (1 μg/ml), josamycin (2 μg/ml), roxithromycin (1 μg/ml), clarithromycin (1 μg/ml), or telithromycin (1 μg/ml). DGKH1 resembling Metamycoplasma hominis formed "fried egg-like colonies" on Mycoplasma solid culture medium. DGKH1 could not be stained by Gram staining. When observed under transmission electron microscopy (TEM) using phosphate buffer as the matrix, the bacteria were spiral-shaped. Results of 16S rRNA gene sequence alignment showed that DGKH1 was highly similar (99.85%) to Spiroplasma eriocheiris CCTCC M 207170 T. However, the urea decomposition test was positive, which was different from all of the known Spiroplasma species. The phylogenetic analysis based on whole genome showed that DGKH1 was clustered in a small branch along with Spiroplasma eriocheiris CCTCC M 207170 T. However, the average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between the two strains were 94.14% and 56.00%, respectively, both below the threshold for prokaryotic species identification. Conclusions:DGKH1 represented a potential new species of genus Spiroplasma, closely related to Spiroplasma eriocheiris. Some microbiological characteristics of DGKH1 were similar to Mycoplasmas. However, the natural host and epidemiological data of DGKH1 need to be further studied.
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The fatality rate of liver failure caused by fatal amanita poisoning is high, and there are no effective antidote drugs in China. On July 30, 2020, the department of infectious diseases and liver diseases of the First People's Hospital of Yunnan Province admitted a 67-year-old female patient with liver failure caused by fatal amanita poisoning. The patient went to the emergency department for treatment due to abdominal pain, vomiting and diarrhea after eating 350-400 g of amanita mushroom for 2 days, accompanied by fatigue for 1 day. There was no abnormality in physical examination. Laboratory indexes: alanine aminotransferase (ALT) 4 798 U/L, aspartate aminotransferase (AST) 10 030 U/L, activated partial thromboplastin time (APTT) 57.5 s, prothrombin time (PT) 72.1 s, international normalized ratio (INR) 8.66, prothrombinactivity (PA) 10%. Based on the patient's medical history, clinical manifestations and laboratory data, the diagnosis was amanita peptide mushroom poisoning and acute liver failure. According to the mechanism of amanita toxin poisoning as enterohepatic circulation, endoscopic retrograde cholangiopancreatography and ultrasound-guided gallbladder puncture and drainage for drainage of bile to discharge toxins were performed to interrupt the enterohepatic circulation of toxins. However, both methods failed, so open cholecystostomy was performed. Because the patient's coagulation function was very poor, artificial hepatic plasma exchange was given to improve coagulation function before open cholecystostomy, and eventually bile was drained successfully. After a total of 19 days of comprehensive medical treatment, the patient was cured and discharged from the hospital, and no sequelae was found after 1 year of follow-up. For such patients, early identification of the disease is required, and blocking the enterohepatic circulation of toxins as soon as possible according to the characteristics and toxicological mechanism of toxins may be the key treatment for rescuing patients with liver failure poisoned by amanita toxin, and it is necessary to combine comprehensive treatments such as active fluid replacement and blood purification to further improve the survival rate.
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Objective:To investigate the application effect of the blended teaching model of "pre-class synchronous small private online course (SPOC)+ flipped classroom+post-class knowledge expansion" in the theoretical teaching of biochemistry and molecular biology. Methods:A total of 951 students majoring in clinical medicine, preventive medicine, and pharmacy in the class of 2020 in Qiqihar Medical College were selected as teaching reform research group (experimental group), and their curriculum relied on the self-built massive open online course (MOOC) curriculum and the MOOC resources of Chinese universities to construct a blended teaching model; the reform methods such as small class grouping, case-based learning, and diversified examination were adopted to carry out theoretical flipped teaching activities with cross integration of cases and knowledge points as the main line. A total of 847 students majoring in clinical medicine, preventive medicine, and pharmacy in the class of 2019 were selected as control group, and the traditional teaching method was used for theoretical courses. The courses were evaluated by offline assessment and online assessment, and feedback information was collected through examination scores, questionnaire survey, and online voting. SPSS 20.0 was used for statistical analysis, and the t-test was used for comparison between groups. Results:The experimental group had a significantly higher total score of final examination than the control group [(92.12±3.88) vs. (86.73±5.27), P<0.05]. The questionnaire survey showed that the students in the experimental group showed a relatively high degree of satisfaction with the blended teaching reform, which increased their participation, experiencing, and sharing activities. The students majoring in clinical medicine in the class of 2020 believed that they had established clinical thinking ability (263, 92.61%) and become familiar with the clinical manifestations and pathogenesis of common diseases (262, 92.25%); the students majoring in preventive medicine in the class of 2020 believed that they had increased their awareness of serving the public (151, 93.21%) and developed the ability to teach and guide healthy living (148, 91.36%); the students majoring in pharmacy in the class of 2020 believed that they had mastered the mechanism of action of drugs for disease treatment (138, 93.24%) and understood the importance of rational drug use in clinical practice (135, 91.22%). Conclusion:The blended teaching model realizes student-centered teaching, stimulates the interest and initiative in learning, and improves learning outcome, thereby improving teaching quality to a certain extent.
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Objective:To explore the application effect of blended learning in clinical practice of undergraduate students majoring in medical imaging diagnosis.Methods:A total of 60 undergraduate students majoring in medical imaging diagnosis who practiced in the Department of Radiology of Chongqing General Hospital from 2017 to 2019 were selected as subjects. The students were divided into experimental group and control group, each with 30 students. During the internship, the experimental group adopted the blended learning, including lecture-based learning, case-based learning, problem-based learning and team-based learning according to different teaching scenarios. While the control group adopted the traditional teaching mode. At the end of the internship, the test scores of the two groups of intern students were compared, and the satisfaction degree of the teaching was investigated by questionnaire. SPSS 19.0 was used to conduct t-test and Chi-square test. Results:The score of theoretical knowledge examination in the experimental group was (90.27±5.38) points, and that in the control group was (83.13±7.57) points. The difference between the two groups was statistically significant ( t=4.21, P<0.001). The score of imaging analysis examination in the experimental group was (90.07 ± 4.80) points, and that in the control group was (82.13±8.71) points. The difference between the two groups was statistically significant ( t=4.37, P<0.001). The results of the satisfaction survey showed that the overall satisfaction with teaching was 76.7% (23/30) in the experimental group and 50.0% (15/30) in the control group, with statistically significant difference ( χ2= 6.57, P=0.037). Conclusion:The blended learning has a good effect in the teaching of undergraduate students majoring in medical imaging diagnosis.
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Objective:To compare the efficacy of pneumovesicoscopic Cohen and Politano-Leadbetter procedures in the treatment of vesicoureteral junction obstruction (VUJO) in children.Methods:The data of 48 children with VUJO who underwent operations in the Department of Urology, Anhui Provincial Children′s Hospital from January 2017 to December 2021 were retrospectively analyzed.According to the operation time, the patients were divided into the pneumovesicoscopic Cohen group(group C) (28 cases) and pneumovesicoscopic Politano-Leadbetter group(group P) (20 cases). The operation time, postoperative urinary catheterization duration, hematuria duration, hospitalization time, and the improvement of hydronephrosis, ureteral dilatation, and renal function after surgery were compared between the 2 groups.The enumeration data were compared by the χ2 test or Fisher′ s exact probability method.The measurement data were compared by the t-test. Results:All the 48 children were successfully operated on by the same surgeon, without conversion to open surgery.Six cases in the group C had a megaureter and underwent ureter tailoring.Two cases in the group P had calyceal and ureteral calculi, which were all removed after operation.There was a statistically significant difference in the operation time between group C and group P[(136.5±35.4) min vs.(165.8±33.2) min, t=-3.154, P=0.002]. The patients were followed up for (10.3±2.6) months after operation.There were 8 cases and 6 cases of urinary tract infection in group C and group P within 2 months after the operation, respectively.They all improved after conservative anti-infection treatment, and the infection was well controlled after removal of the D-J tube.Besides, their intravenous pyelography 6 months after operation showed that the ureter was unobstructed.In group C, 6 months after the operation, the anterior and posterior diameters of the renal pelvis [(1.62±0.54) cm vs.(2.55±1.24) cm, t=-5.027, P=0.001] and the largest diameter of the ureter [(0.95±0.27) cm vs.(1.51±0.52) cm, t=-8.495, P<0.001] were significantly decreased, compared with those before operation.However, the renal cortex thickness was increased significantly [(1.47±0.25) cm vs.(0.86±0.46) cm, t=2.028, P=0.004], and the renal function (as indicated by the diuretic nephrogram) was notably improved [(46.27±2.16)% vs.(41.83±3.04)%, t=1.647, P=0.030]. In group P, 6 months after operation, the anterior and posterior diameters of the renal pelvis[(1.48±0.82) cm vs.(2.68±1.41) cm, t=-2.740, P=0.003] and the maximum diameter of the ureter [(1.05±0.46) cm vs.(1.36±0.27) cm, t=-1.635, P=0.040] were significantly smaller than those before operation.However, the renal cortical thickness was increased [(1.38±0.33) cm vs.(0.74±0.39) cm, t=9.073, P<0.001], and the renal function (as indicated by the diuretic nephrogram) was significantly improved [(45.18±3.35)% vs.(39.55±2.49)%, t=1.277, P=0.030]. Politano-Leadbetter surgery outperformed Cohen surgery in promoting the recovery of the anterior and posterior diameters of the renal pelvis [(1.48±0.82) cm vs.(1.62±0.54) cm, t=-1.748, P=0.030]. Conclusions:Pneumovesicoscopic Politano-Leadbetter operation can establish a longer submucosal tunnel without changing the ureteral shape and opening position, having good effects in treating VUJO combined with calyceal and ureteral calculi.Pneumovesicoscopic Politano-Leadbetter operation can also better improve postoperative recovery from hydronephrosis than Cohen operation.However, the pneumovesicoscopic Politano-Leadbetter operation is more difficult and requires longer time.The surgeon should choose a reasonable operation based on his/her own experience.
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Objective:To investigate the relationship between central venous-arterial blood carbon dioxide partial pressure difference (Pcv-aCO 2) and left ventricular ejection fraction(LVEF) in acute myocardial infarction. Methods:Clinical data of patients with acute myocardial infarction admitted to the Intensive Care Unit of Fujian Provincial Hospital from November 2019 to October 2021 were retrospectively analyzed. LVEF was measured by bedside echocardiogram. The patients were divided into the normal LVEF group (LVEF ≥ 52%) and decreased LVEF group (LVEF < 52%) according to LVEF. The differences in general information and hemodynamic parameters between the two groups were compared. The normality of the above data was tested by the Jarque-Bera test. Correlation analysis of hemodynamic indices with LVEF was performed. Binary logistic regression was used to analyze the risk factors associated with the decrease in LVEF. The feasibility of diagnosing LVEF decline with Pcv-aCO 2 was assessed using receiver operating characteristic (ROC) curve. Results:Seventy-two patients with acute myocardial infarction were included for analysis, including 25 patients in the normal LVEF group and 47 patients in the decreased LVEF group. Pcv-aCO 2 was significantly higher in the decreased LVEF group than that in the normal LVEF group [(7.13±1.19) mmHg vs. (5.41±1.23) mmHg, P<0.01]. There was a negative correlation between LVEF and Pcv-aCO 2 ( rs= -0.740, P<0.01). The area under the ROC curve for Pcv-aCO 2 was 0.849 (95% CI: 0.758-0.939, P<0.01). The binary logistic regression analysis showed that Pcv-aCO 2 was an independent risk factor for decreased LVEF ( OR=2.251, 95% CI: 1.326-3.820). Conclusions:To a certain extent, the increase of Pcv-aCO 2 can predict the decrease of LVEF in acute myocardial infarction.
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Taking the recommendations development of the World Federation of Acupuncture-Moxibustion Societies (WFAS) standard Clinical Practice Guideline for Female Urinary Incontinence as an example, this study analyzed the consensus expert composition, specific consensus process, and results in the development of the guideline's recommendations. It systematically examined the advantages of using the modified Delphi method in the formation of recommendations for acupuncture and moxibustion clinical practice guideline, with the aim of providing reference for the development of acupuncture and moxibustion guidelines in the same field.
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Femenino , Humanos , Acupuntura , Terapia por Acupuntura , Técnica Delphi , MoxibustiónRESUMEN
【Objective】 To investigate the safety, feasibility and clinical efficacy of modified anterior robot-assisted laparoscopic radical prostatectomy (RALRP) with preservation of Retzius space. 【Methods】 The clinical data of 10 patients who underwent RALRP using the modified anterior approach to preserve the Retzius space in our hospital during June 2021 and March 2022 were retrospectively analyzed, including the preoperative, intraoperative, postoperative and follow-up data. 【Results】 All operations were successful without conversion to open surgery. The average operation time (robotic arm operation time) was (98.6±47.7) min, blood loss (105.0±57.3) mL, postoperative drainage tube indwelling time (5.3±1.3) d, postoperative urinary catheter indwelling time (7.2±0.8) d, and postoperative hospital stay (9.2±2.2) d. Urinary continence was achieved immediately after removal of the urinary catheter in 6 patients, 2 patients recovered 2 weeks after extubation, and 2 patients recovered 3 months after extubation. Postoperative pathology showed pT2a stage in 1 case, pT2b stage in 2 cases, and pT2c stage in 7 cases; Gleason score was 6-7 points; all postoperative resection margins were negative. During the follow-up of 3-12 months, no tumor recurrence was observed, and no patient was readmitted due to surgical complications. 【Conclusion】 RALRP with modified anterior approach to preserve the Retzius space is safe and feasible, with no serious complications during and after surgery, and the early postoperative urinary continence effect is comparable to that of the posterior approach.
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Objective To summarize the clinical features of a family with Basan syndrome and to analyze mutation of the SMARCAD1 gene. Methods The Basan family was diagnosed at Dermatology Hospital, Southern Medical University in 2022. Backgroud data was collected, and clinical and genetic characteristics were analyzed. Meanwhile, a retrospective analysis of features and associated genetic mutations reported in all patients with Basan syndrome was conducted. Results A total of 18 patients with Basan syndrome were identified, including 9 males and 9 females. All 18 patients had no fingerprints at birth (18/18, 100%), and some patients had knuckle pads, palmoplantar hyperkeratosis, nail atrophy, nail separation, and longitudinal nail ridges. Symptoms vary in severity. At the same time, it was found that c.-10+1G > T (as well as c.378+1G > T)mutations appeared on the intron 1 of the SMARCAD1 (NM_020159.5) gene in 7 patients, resulting in abnormal splicing. Conclusions This article provides help for the early diagnosis of Basan syndrome and helps to improve the diagnosis and differentiation level of clinicians.
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Purpose@#Elevated plasma D-dimer level is a poor prognostic factor for many solid tumors. However, limited research has been conducted on D-dimer in children with neuroblastoma (NB), and its clinical significance remains unclear. The present study investigated the clinical and prognostic significance of D-dimer in pediatric NB patients. @*Methods@#A retrospective analysis of all newly admitted NB patients was conducted from January 2014 to December 2020.Baseline clinicopathological features, preoperative laboratory parameters, and follow-up information were collected. Univariate and multivariate analyses were performed to determine the relationship between D-dimer level, clinical features, and the prognostic value. @*Results@#Among 266 patients, the median value of D-dimer was 2.98 ng/mL, of which 132 patients showed elevated D-dimer levels before surgery (>2.98 ng/mL). Univariate analysis revealed that elevated D-dimer was significantly associated with age, hemoglobin, neutrophil-to-lymphocyte ratio, neuron-specific enolase, 24-hour vanillylmandelic acid, overall survival, and so on (P < 0.05). Patients with elevated D-dimer levels had shorter median overall survival time when compared with normal D-dimer levels (P = 0.01). The prognosis was better in patients with normal D-dimer levels when combined with lower age, ganglioneuroblastoma tumor type, lower stage on International Neuroblastoma Staging System, low-risk group, and without bone metastasis or bone marrow metastasis. The continuous increase of D-dimer level after treatment indicated tumor recurrence or progression. @*Conclusion@#A high D-dimer level is associated with low overall survival, and an elevated D-dimer level after treatment indicates tumor recurrence and progression. D-dimer can be used as one of the evaluation factors for NB treatment or prognosis.
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Aim To analyze the genotype-phenotype characteristics of voltage-gated potassium channels (Kv) associated genetic epilepsy and evaluate the efficacy of anti-seizure medications(ASMs). Methods PubMed database was searched and patients meeting the inclusion criteria were included for analysis. We divided the patients into “benign”, “encephalopathic” and other phenotypes according to the clinical characteristics. We performed descriptive statistical analysis of patients' mutated genes, clinical phenotype and drug efficacy, and used logistic regression to explore the influencing factors of treatment outcome. Results Data of 474 children were included for analysis. There were significant differences among different phenotypes in mutated genes, source of mutations and so on. In terms of clinical characteristics, there were also significant differences between patients with different phenotypes in age of onset, combined developmental delay and so on. In terms of monotherapy, phenobarbital was the most common treatment choice for children with “benign” phenotype, and sodium channel blockers (SCBs) were the most common treatment choice for children with “encephalopathy” phenotype, and the efficacy of SCBs monotherapy was superior to that of other ASMs. Multivariate Logistic analysis of the children receiving monotherapy showed that whether the children were combined with developmental delay and whether SCBs were used were significant factors influencing the efficacy of drug therapy. Conclusions Patients with the “benign” and “encephalopathic” phenotypes differ in several aspects of genetic variation, clinical characteristics, and drug selection. These results suggest that SCBs may be one of the recommended options for monotherapy.
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Aim To explore the mechanism of grape seed proanthocyanidins (GSPs) targeting astrocytes (AS), so as to regulate the phenotype and function of AS and maximize their neuroprotective effect. Methods The effects of GSPs on the phenotype, secretion of pro-inflammatory factors and neurotrophic factors of Al AS induced by TNF-α, IL-1α and Clq were investigated by RT-PCR, Elisa and Western blot in vitro. And JNK phosphorylation was determined using Western blot. Results GSPs significantly reduced the expression of C3d and Clq of Al AS markers and inhibited the phosphorylation of JNK. Moreover, compared with the model group, GSPs could significantly inhibit the release of pro-inflammatory cytokines IL-6, IL-1 α, IL-17 and H
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Aim To explore the protective effect of proanthocyanidin B2 (PC-B2) on oxidative damage of PC 12 cells induced by hydrogen peroxide (H
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Aim To explore the protective effects of ganoderma lucidum polysaccharides (GLPS) on experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS) and the underlying mechanism. Methods Thirty C57BL/6 mice were randomly divided into three groups: normal control group, EAE model group and GLPS group (5 mg • kg
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The purpose of this study was to investigate the effect of notoginsenoside R_1(NGR_1) on alleviating kidney injury by regulating renal oxidative stress and the Nrf2/HO-1 signaling pathway in mice with IgA nephropathy(IgAN) and its mechanism. The mouse model of IgAN was established using a variety of techniques, including continuous bovine serum albumin(BSA) gavage, subcutaneous injections of carbon tetrachloride(CCl_4) castor oil, and tail vein injections of lipopolysaccharide(LPS). After successful modeling, mice with IgAN were randomly separated into a model group, low, medium, and high-dose NGR_1 groups, and a losartan group, and C57BL6 mice were utilized as normal controls. The model and normal groups were given phosphate buffered saline(PBS) by gavage, the NGR_1 groups were given varying dosages of NGR_1 by gavage, and the losartan group was given losartan by gavage for 4 weeks. The 24-hour urine of mice was collected after the last administration, and serum and kidney tissues of mice were taken at the end of the animal experiment. Then urine red blood cell count(URBCC), 24-hour urine protein(24 h protein), serum creatinine(Scr), and blood urea nitrogen(BUN) levels were measured. The enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of galactose-deficient IgA1(Gd-IgA1), kidney injury molecule 1(Kim-1), and neutropil gelatinase-associated lipocalin(NGAL) in the mouse serum. The assay kits were used to detect the levels of malondialdehyde(MDA) and superoxide dismutase(SOD), and immunofluorescence(IF) was used to detect the expression level of glutathione peroxidase 4(GPX4) in the mesangial region. Western blot was used to detect the protein expression of nuclear transcription factor E2 related factor 2(Nrf2)/heme oxygenase 1(HO-1) signaling pathway in the renal tissue. Hematoxylin-eosin(HE) staining was used to observe pathological alterations in the glomerulus of mice. The results revealed that, as compared with the model group, the serum Gd-IgA1 level, URBCC, 24 h protein level, renal damage markers(Kim-1 and NGAL) in the high-dose NGR_1 group decreased obviously and renal function indicators(BUN, Scr) improved significantly. The activity of SOD activity and expression level of GPX4 increased significantly in the high-dose NGR_1 group, whereas the expression level of MDA reduced and protein expression levels of Nrf2 and HO-1 increased. Simultaneously, HE staining of the renal tissue indicated that glomerular damage was greatly decreased in the high-dose NGR_1 group. In conclusion, this study has clarified that NGR_1 may alleviate the kidney injury of mice with IgAN by activating the Nrf2/HO-1 signaling pathway, improving antioxidant capacity, and reducing the level of renal oxidative stress.
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BACKGROUND@#Exploring the underlying mechanism of rituximab resistance is critical to improve the outcomes of patients with diffuse large B-cell lymphoma (DLBCL). Here, we tried to identify the effects of the axon guidance factor semaphorin-3F (SEMA3F) on rituximab resistance as well as its therapeutic value in DLBCL.@*METHODS@#The effects of SEMA3F on the treatment response to rituximab were investigated by gain- or loss-of-function experiments. The role of the Hippo pathway in SEMA3F-mediated activity was explored. A xenograft mouse model generated by SEMA3F knockdown in cells was used to evaluate rituximab sensitivity and combined therapeutic effects. The prognostic value of SEMA3F and TAZ (WW domain-containing transcription regulator protein 1) was examined in the Gene Expression Omnibus (GEO) database and human DLBCL specimens.@*RESULTS@#We found that loss of SEMA3F was related to a poor prognosis in patients who received rituximab-based immunochemotherapy instead of chemotherapy regimen. Knockdown of SEMA3F significantly repressed the expression of CD20 and reduced the proapoptotic activity and complement-dependent cytotoxicity (CDC) activity induced by rituximab. We further demonstrated that the Hippo pathway was involved in the SEMA3F-mediated regulation of CD20. Knockdown of SEMA3F expression induced the nuclear accumulation of TAZ and inhibited CD20 transcriptional levels via direct binding of the transcription factor TEAD2 and the CD20 promoter. Moreover, in patients with DLBCL, SEMA3F expression was negatively correlated with TAZ, and patients with SEMA3F low TAZ high had a limited benefit from a rituximab-based strategy. Specifically, treatment of DLBCL cells with rituximab and a YAP/TAZ inhibitor showed promising therapeutic effects in vitro and in vivo .@*CONCLUSION@#Our study thus defined a previously unknown mechanism of SEMA3F-mediated rituximab resistance through TAZ activation in DLBCL and identified potential therapeutic targets in patients.