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AIM: To explore the mechanism of fructus lycii in treating dry eye based on network pharmacology and experimental verification.METHODS: Taking “fructus lycii” as key words, the active ingredients and target of fructus lycii were searched by using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). Gene targets related to dry eye(DE)were searched by GeneCards and OMIM databases. The target genes of fructus lycii and DE were imported into Venn software to obtain the intersection target map of them. After that, the data were imported into the String database to obtain the PPI protein-protein interaction network diagram. Using Cytoscape3.7.2 software, the PPI protein-protein interaction network diagram was constructed for active ingredients, target sites and related diseases of fructus lycii. The Bioconductor platform and R language were used for gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis. And the key targets in the pathogenesis of DE were verified by experiments.RESULTS: Through TCMSP, 45 types of effective chemical components of fructus lycii, 174 target genes corresponding to active components and 131 common target genes with DE were screenedout. In accordance with the network topology of “drug-composition-disease-target”, 27 main effective components of fructus lycii were found in the treatment of DE. The PPI network was analyzed according to the high degree value, which is the key targets of fructus lycii for DE treatment, mainly including AKT1, VEGFA, CASP3, IL1B, JUN, PTGS2, CXCL8, etc. According to GO enrichment analysis, 166 biological functions and processes of fructus lycii for DE treatment were obtained. KEGG enrichment analysis showed that 31 signaling pathways were involved. Additionally, experimental verification displayed that the protein expressions of AKT1, interleukin-6(IL-6), tumor necrosis factor(TNF-α)and IL-17 in conjunctiva tissue of the DE model group were significantly increased.CONCLUSIONS: Through network pharmacology, this study confirmed that the treatment of DE by fructus lycii is a complex process involving multi-components, multi-targets and multi-pathways, and that the treatment of DE by fructus lycii is mainly regulated by anti-inflammatory and apoptosis-related molecules.
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Peripheral T-cell lymphoma (PTCL) is a group of heterogeneous malignant tumors with poor prognosis, with a lack of standard treatment regimen and poor efficacy of traditional chemotherapy. Therefore, finding new and more effective therapeutic targets to improve the efficacy of PTCL is an urgent clinical problem. In recent years, as the exploration of PTCL at the genetic and molecular levels has intensified, novel therapeutic targets based on gene alterations and molecular typing have been identified. This article summarizes the research progress of main gene alterations and molecular typing of PTCL in recent years.
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Objective: To investigate the characteristics of electromyography (EMG) signals and the starting threshold voltages of the orbicularis oris muscles (OOM) in healthy rhesus monkeys under different muscle movement conditions. Methods: The EMG signals and the starting threshold voltages at different time points in 4 healthy rhesus monkeys were acquired and recorded with EMG device and evoked potentiometer. The voltage amplitude variation of EMG signals was analyzed, and the voltage amplitude range of EMG signals at the beginning of OOM contraction was established. The data were statistically analyzed by one-way ANOVA. Results: The EMG of OOM in healthy monkeys in the quiet, natural and continuous mouth-closed state was linear and relatively stable, and the absolute value fluctuated between 15 and 50 μV. The EMG waveform increased rapidly during the natural lip contraction movement, and its amplitude fluctuated greatly, with the highest absolute value of the peak value reaching hundreds of microvolts. The amplitude of EMG induced by continuous mouth closure was more than thousands of microvolts. There was no significant difference in EMG amplitudes of OOM in the healthy rhesus monkey under quiet and continuous lip closure at different time points (P>0.05). There was no significant difference in threshold voltages in the state of natural lip contraction of bilateral OOM at different time points (average range: 57.17-57.47 μV) in the healthy rhesus monkeys (P>0.05). There was no significant difference in threshold voltages of OOM induced by bilateral OOM at different time points(average range: 55.38-55.99 μV) in the healthy rhesus monkeys(P>0.05). There were significant differences in the absolute values of EMG amplitudes of OOM between the three lip movement modes: (30.67±8.72) μV in quiet and natural continuous lip closure (475.12±54.72) μV in natural lip contraction, and (921.22±312.79) μV in the induced persistent lip closure, with t values of -8.48, -9.35 and -5.01 respectively, all P<0.001. Conclusions: The EMG signals of OOM show different characteristics under different muscle movement conditions, which can be used as a basis for computer to judge and recognize the movement conditions of OOM. The upper limits of the EMG threshold voltage values of OOM under different motion states are 55-60 μV.
Subject(s)
Animals , Lip , Macaca mulatta , Facial Muscles , ElectromyographyABSTRACT
Objective: To analyze whether the upper airway of patients with catathrenia has obstructive manifestations using nasal resistance, craniofacial, and upper airway imaging methods, which could benefit the exploration of the etiology and treatment options. Methods: From August 2012 to September 2019, a total of 57 patients with catathrenia in the Department of Orthodontics at Peking University Hospital of Stomatology were included in the study, including 22 males and 35 females, aged (31.1±10.9) years, with a body mass index of (21.7±2.7) kg/m2. All the patients were diagnosed by full-night polysomnography at the Sleep Division, Peking University People's Hospital, of which 10 patients were combined with obstructive sleep apnea hypopnea syndrome (OSAHS). The median groaning index of patients was 4.8 (1.8, 13.0) events/h. Nasal resistance and cone-beam CT were conducted on the patients, and measurements were performed on the craniofacial structures, upper airway, and surrounding soft tissues, compared with non-snoring normal occlusion individuals' references published by the same research team (144 college students recruited at Peking University and 100 non-snoring young adults with normal occlusion recruited at six universities in Beijing). Results: The total nasal resistance of patients with catathrenia was (0.26±0.08) Pa·cm-3·s-1. The patients had overall well-developed mandibular hard tissues. However, the patients were found with increased FH/BaN (steep anterior cranial base plane), increased MP/FH (forward rotation of the mandible); increased U1/NA and L1/MP (proclined upper and lower incisors). The sagittal diameter of the velopharynx [(19.2±4.5) mm] was significantly larger than the normal reference (t=8.44, P<0.001), while the sagittal diameter at the hypopharynx [(17.4±6.4) mm] was statistically smaller than the normal reference (t=-2.79, P=0.006). Catarhrenia patients combined with OSAHS presented longer soft palate, tongue, and lower hyoid bone than those with primary catathrenia. Conclusions: In patients with catathrenia, the overall craniofacial characteristics are well-developed skeletal structures, lower nasal resistance, proclined upper and lower incisors, wide upper sagittal development of the upper airway and narrow hypopharynx. Groaning sounds might be related to the narrowing of the hypopharynx during sleep.
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Objective: To explore the characteristics of Banna miniature pig liver failure induced by amanita exitialis. Methods: From September to October 2020, a reverse high performance liquid chromatography (RP-HPLC) method was used to determine the toxin content of amanita exitialis solution, and 2.0 mg/kg amanita exitialis solution (α-amanitins+β-amanitins) was administered orally to Banna miniature pigs. Toxic symptoms, blood biochemical indexes and histopathological changes of liver, heart and kidney were observed at each time point. Results: All Banna miniature pigs died within 76 h of exposure, and different degrees of digestive tract symptoms such as nausea, vomiting and diarrhea appeared between 6 and 36 h. The biochemical indexes of alanine aminotransferase, aspartate aminotransferase, total bilirubin, lactate dehydrogenase, myoglobin, creatine kinase isoenzyme, blood urea nitrogen and creatinine increased significantly at 52 h after exposure, and the differences were statistically significant compared with 0 h (P<0.05). The bleeding of liver and heart was obvious under macroscopic and microscopic observation, hepatocyte necrosis, renal tubule epithelial cell swelling. Conclusion: Large dose of amanita exitialis can cause acute liver failure of Banna miniature pigs, which is in line with the pathophysiological characteristics of acute liver failure, and lays a foundation for further research on the toxic mechanism and detoxification drugs of amanita exitialis induced liver failure.
Subject(s)
Animals , Swine , Amanitins/metabolism , Swine, Miniature/metabolism , Amanita/metabolism , Liver Failure, Acute , Mushroom Poisoning/diagnosisABSTRACT
ObjectiveTo discuss the diagnostic methods of global developmental delay caused by 10q24.3 heterozygous loss. MethodsA retrospective analysis was conducted on the clinical data of one child with global developmental delay， and the results of low depth whole-genome copy number variation sequencing （CNVseq） and family whole exome sequencing （WES） of the child and his parents. ResultsThe patient was a 10-month-old male with developmental retardation in four areas， with some special features （ocular hypertelorism， strabismus， flat nose bridge， protruding forehead， cleft palate， high palatal arch， etc.） and hypotonia of limbs. The CNVseq and WES test showed that the patient had new 10q24.3 heterozygosis loss. Because this region contains the gene SUFU associated with basal cell nevus syndrome and the gene CNNM2 associated with hypomagnesemia， seizures， and mental retardation， and the gene TRIM8 associated of Focal segmental glomerulosclerosis with neurodevelopmental syndrome， we speculated that the cause of the disease in the child was highly related to the heterozygosity deletion of SUFU gene and CNNM2 gene and TRIM8 gene. ConclusionGenetic testing should be improved as soon as possible for children with global developmental delay and special facial manifestations， so as to make clear diagnosis and to judge prognosis.
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OBJECTIVES@#To study the role of plasma exchange combined with continuous blood purification in the treatment of refractory Kawasaki disease shock syndrome (KDSS).@*METHODS@#A total of 35 children with KDSS who were hospitalized in the Department of Pediatric Intensive Care Unit, Hunan Children's Hospital, from January 2019 to August 2022 were included as subjects. According to whether plasma exchange combined with continuous veno-venous hemofiltration dialysis was performed, they were divided into a purification group with 12 patients and a conventional group with 23 patients. The two groups were compared in terms of clinical data, laboratory markers, and prognosis.@*RESULTS@#Compared with the conventional group, the purification group had significantly shorter time to recovery from shock and length of hospital stay in the pediatric intensive care unit, as well as a significantly lower number of organs involved during the course of the disease (P<0.05). After treatment, the purification group had significant reductions in the levels of interleukin-6, tumor necrosis factor-α, heparin-binding protein, and brain natriuretic peptide (P<0.05), while the conventional group had significant increases in these indices after treatment (P<0.05). After treatment, the children in the purification group tended to have reductions in stroke volume variation, thoracic fluid content, and systemic vascular resistance and an increase in cardiac output over the time of treatment.@*CONCLUSIONS@#Plasma exchange combined with continuous veno-venous hemofiltration dialysis for the treatment of KDSS can alleviate inflammation, maintain fluid balance inside and outside blood vessels, and shorten the course of disease, the duration of shock and the length of hospital stay in the pediatric intensive care unit.
Subject(s)
Humans , Child , Plasma Exchange , Mucocutaneous Lymph Node Syndrome/therapy , Continuous Renal Replacement Therapy , Renal Dialysis , Plasmapheresis , ShockABSTRACT
OBJECTIVES@#To study the application value of transport ventilator in the inter-hospital transport of critically ill children.@*METHODS@#The critically ill children in Hunan Children's Hospital who were transported with or without a transport ventilator were included as the observation group (from January 2019 to January 2020; n=122) and the control group (from January 2018 to January 2019; n=120), respectively. The two groups were compared in terms of general data, the changes in heart rate, respiratory rate, and blood oxygen saturation during transport, the incidence rates of adverse events, and outcomes.@*RESULTS@#There were no significant differences between the two groups in sex, age, oxygenation index, pediatric critical illness score, course of disease, primary disease, heart rate, respiratory rate, and transcutaneous oxygen saturation before transport (P>0.05). During transport, there were no significant differences between the two groups in the changes in heart rate, respiratory rate, and transcutaneous oxygen saturation (P>0.05). The incidence rates of tracheal catheter detachment, indwelling needle detachment, and sudden cardiac arrest in the observation group were lower than those in the control group during transport, but the difference was not statistically significant (P>0.05). Compared with the control group, the observation group had significantly shorter duration of mechanical ventilation and length of stay in the pediatric intensive care unit and significantly higher transport success rate and cure/improvement rate (P<0.05).@*CONCLUSIONS@#The application of transport ventilator in the inter-hospital transport can improve the success rate of inter-hospital transport and the prognosis in critically ill children, and therefore, it holds promise for clinical application in the inter-hospital transport of critically ill children.
Subject(s)
Child , Humans , Critical Illness , Respiration, Artificial/adverse effects , Intensive Care Units, Pediatric , Ventilators, Mechanical , PrognosisABSTRACT
Objective@#To describe the prevalence of overweight and obesity among children and adolescents in Jinan City according the national and international criteria, as well as to compare the Chinese and international standards, so as to provide basic data for relevant intervention strategies.@*Methods@#From September to December 2021, using the height and weight data obtained from the health checkup reports of 746 985 primary and secondary school students in Jinan City in 2021, body mass index(BMI) was calculated to evaluate the current status of the prevalence of overweight and obesity among this sample of children and adolescents aged 6- 18 years old. The consistency of the Chinese standard, U.S. Centers for Disease Control and Prevention (CDC) standard, International Obesity Task Force (IOTF) standard, and World Health Organization (WHO) standard was compared by calculating the weighted Kappa value.@*Results@#Based on the Chinese, U.S. CDC, IOTF and WHO standards, the overweight rates of children and adolescents aged 6-18 years in Jinan were 17.3%, 16.5%, 21.1% and 13.6%, respectively, and the obesity rates were 23.1%, 19.5%, 13.5% and 6.6%, respectively. The overweight and obesity rates of boys were higher than those of girls under the four criteria (China: χ 2=1 418.48, 9 868.51, U.S. CDC: χ 2=145.78, 23 211.41, IOTF: χ 2=1 326.94, 13 615.62, WHO: χ 2=873.13, 46.41, P <0.01).The overweight rate of adolescents in the 13-18 year-old age group was higher than that of children aged 6-12 years (China: χ 2=29.13, U.S. CDC: χ 2=6.43, IOTF: χ 2=15.87, WHO: χ 2=19.48, P <0.01) and the obesity rate of the group aged 6-10 years was significantly higher than that of the group aged 11-18 years (China: χ 2=217.02, U.S. CDC: χ 2=227.54, IOTF: χ 2=171.91, WHO: χ 2=165.91, P <0.01). The rates of overweight and obesity in urban children and adolescents were slightly higher than those in rural children and adolescents (China: χ 2=25.06, 245.12, U.S. CDC: χ 2=56.13, 205.93, IOTF: χ 2= 182.34 , 22.04, WHO: χ 2=200.88, 21.61, P <0.01). The Chinese standard showed good agreement with the IOTF standard and U.S. CDC standard, with weighted Kappa values of 0.72 and 0.83, but poor agreement with the WHO standard, with a weighted Kappa value of 0.33.@*Conclusion@#The current prevalence of overweight and obesity among children and adolescents in Jinan is serious. The Chinese standard has good consistency with IOTF standard and American CDC standard, and poor consistency with WHO standard.
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Objective To investigate the effects of nitroquine on the development of different stages of Plasmodium yoelii in Anopheles stephensi. Methods An. stephensi mosquitoes were fed with conventional sucrose water or sucrose water containing 100 μmol/L nitroquine one day prior to P. yoelii infection. Following starvation for 24 hours, mosquitoes were fed with the blood of Kunming mice infected with P. yoelii, and the number of oocysts was observed in the stomach of An. stephensi. After 6 days and 14 days of infection, the mosquitoes were starved for 24 hours, and then fed with conventional sucrose water or nitroquine treated sucrose water. The An. stephensi mosquitoes were starved for 24 hours 6 and 14 days post-infection with P. yoelii, and then fed with conventional sucrose water or nitroquine-containing sucrose water, the numbers of P. yoelii sporozoites were examined in the hemolymph and salivary glands of An. stephensi. Results Following exposure to nitroquine-containing sucrose water one day prior to P. yoelii infections, the number of P. yoelii oocysts was significantly lower in the An. stephensi stomach on day 7 (119.2 ± 16.1 vs. 207.3 ± 21.8; t = 3.207, P < 0.05). After conventional sucrose water was ceased for 24 hours on day 6, and An. stephensi was fed with nitroquine-containing sucrose water, the number of P. yoelii sporozoites peaked in the hemolymph on day 14 in the nitroquine treatment group (952.3 ± 22.7) and on day 12 in the sucrose water treatment group (1 287.0 ± 39.0), and there was a significant difference in the number of sporozoites in the salivary glands between the nitroquine treatment group and the sucrose water treatment group (9 467.0 ± 1 304.0 vs. 10 533.0 ± 758.7; t = 0.707, P = 0.506) on day 17. After conventional sucrose water was ceased for 24 hours on day 14, and An. stephensi was fed with nitroquine-containing sucrose water, the number of sporozoites in the salivary glands was significantly greater in the nitroquine treatment group than in the sucrose water treatment group (21 900.0 ± 2 613.0 vs. 10 533.0 ± 732.3; t = 4.188, P < 0.05). Conclusions Nitroquine treatment exhibits diverse effects the development of different stages of P. yoelii, and nitroquine treatment may reduce the transmission of P. yoelii in uninfected An. stephensi.
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On October, 2021, the WHO announced the recommendation of RTS, S/AS01 for use among children living in moderately and highly malaria-endemic areas, which receives global attention. Here, the history of RTS, S/AS01 vaccine development and its role in malaria control are described.
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@#Diagnosis of early keratoconus(KC)contributes to identifying potential patients before typical clinical symptoms. It also contributes to timely intervention of the progress of disease and improvement of long-term prognosis. Hence, it is crucial to prevent iatrogenic corneal ectasia and reduce the burden of keratoplasty. There are diverse kinds of early KC diagnosis techniques, including corneal topography, corneal aberrations, epithelial and corneal thickness measurement, corneal confocal microscopy, corneal biomechanics, and genetic examination. Since it is often difficult to ensure sufficient sensitivity and specificity with single technique, multiple techniques are beneficial to evaluate the cornea comprehensively, which may become the development tendency of early KC diagnosis in the future.
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Sophora alopecuroides, a plant of the family Leguminosae, is one of the Daodi herbs in Ningxia. The active constituents of Sophora alopecuroides are abundant and complex, including alkaloids, flavonoids, volatile oils, steroids, polysaccharides, fatty acids and so on. In recent decades, a great number of domestic and overseas studies have been carried out on Sophora alopecuroides alkaloids, which have anti-hepatitis, anti-liver fibrosis, anti-cirrhosis, anti-liver failure and anti-liver cancer and other pharmacological effects. Clinically, Matrine-related drugs are used to treat hepatitis B virus infection and other diseases. This review aims to summarize the main active ingredients of Sophora alopecuroides, mainly focusing on the research progress in their treatment activities for liver diseases.
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MicroRNA (miRNA) plays an important role in the development of diffuse large B-cell lymphoma (DLBCL) by binding to the 3′ non-coding region of the target gene mRNA to regulate gene expression after transcription. The expression level of miRNA is closely related to the clinical staging, typing, prognosis assessment, and therapeutic effect of DLBCL. miRNA has a great potential as that of DLBCL-related biomarkers, and because of the close link between the two, miRNA-based therapies are expected to lead to new treatment options for DLBCL patients.
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AIM: To study the effects of the specific simulated luminous environment on the visual performance of people with different vision, so as to provide an experimental basis for revising pilots' vision standards. METHODS: A controlled randomized trial was conducted. Twenty-four volunteers were recruited and divided into four groups(1.0/1.0, 0.8/0.8, 0.6/0.6 and 0.4/0.4, decimal vision)according to right/left eye visual acuity, with six subjects in each group. Each subject was tested for static distant vision, kinetic visual acuity, color vision, depth perception error and visual search time under the simulated luminous environments of sunlight, twilight, and on-cloud, respectively, to compare changes in the impact of distinctive luminous surroundings on the visual performance indicators of human beings with different vision.RESULTS: There were main effect differences in static distant vision, kinetic visual acuity, color error, depth perception error and visual search time under different light environments(all P<0.01). The binocular static distant visual acuity, abilities of color discrimination, depth perception and visual search in simulated sunlight environment were higher than those in simulated twilight and on-cloud environments. In the 0.4/0.4 vision group, kinetic vision in simulated twilight and on-cloud environments were significantly lower than that in simulated sunlight environment(P<0.01). There were main effect differences in binocular static distant vision, kinetic visual acuity, depth perception error and visual search time among subjects with different vision(all P<0.05). Compared with 1.0/1.0 vision group, those with 0.6/0.6 and 0.4/0.4 vision had significant decrease in kinetic visual acuity, depth perception ability and visual search ability(all P<0.05). CONCLUSION: Different luminous environments have a great impact on the visual performance of people with low vision, which poses a potential threat to flight safety.
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Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular mortality in patients with diabetes mellitus but the protective mechanism remains elusive. Here we demonstrated that the SGLT2 inhibitor, Empagliflozin (EMPA), suppresses cardiomyocytes autosis (autophagic cell death) to confer cardioprotective effects. Using myocardial infarction (MI) mouse models with and without diabetes mellitus, EMPA treatment significantly reduced infarct size, and myocardial fibrosis, thereby leading to improved cardiac function and survival. In the context of ischemia and nutritional glucose deprivation where autosis is already highly stimulated, EMPA directly inhibits the activity of the Na+/H+ exchanger 1 (NHE1) in the cardiomyocytes to regulate excessive autophagy. Knockdown of NHE1 significantly rescued glucose deprivation-induced autosis. In contrast, overexpression of NHE1 aggravated the cardiomyocytes death in response to starvation, which was effectively rescued by EMPA treatment. Furthermore, in vitro and in vivo analysis of NHE1 and Beclin 1 knockout mice validated that EMPA's cardioprotective effects are at least in part through downregulation of autophagic flux. These findings provide new insights for drug development, specifically targeting NHE1 and autosis for ventricular remodeling and heart failure after MI in both diabetic and non-diabetic patients.
Subject(s)
Animals , Humans , Mice , Diabetes Mellitus , Diabetes Mellitus, Type 2/drug therapy , Glucose , Myocardial Infarction/metabolism , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Ventricular RemodelingABSTRACT
OBJECTIVES@#To investigate the efficacy and application value of plasma exchange as an adjuvant therapy in children with hemophagocytic syndrome (HPS).@*METHODS@#A prospective randomized controlled trial was designed. Forty children with severe HPS were enrolled, who were treated in the pediatric intensive care unit (PICU) of Hunan Children's Hospital from October 2018 to October 2020. The children were randomly divided into a plasma exchange group and a conventional treatment group using a random number table, with 20 children in each group. The children in the conventional treatment group received etiological treatment and conventional symptomatic supportive treatment, and those in the plasma exchange group received plasma exchange in addition to the treatment in the conventional treatment group. The two groups were compared in terms of general information, clinical symptoms and signs before and after treatment, main laboratory markers, treatment outcome, and prognosis.@*RESULTS@#Before treatment, there were no significant differences between the two groups in gender, age, course of the disease before admission, etiological composition, pediatric critical illness score, involvement of organ or system functions, and laboratory markers (P>0.05). After 7 days of treatment, both groups had remission and improvement in clinical symptoms and signs. After treatment, the plasma exchange group had significantly lower levels of C-reactive protein, procalcitonin, and serum protein levels than the conventional treatment group (P<0.05). The plasma exchange group also had significantly lower levels of alanine aminotransferase and total bilirubin than the conventional treatment group (P<0.05). The length of stay in the PICU in the plasma exchange group was significantly shorter than that in the conventional treatment group (P<0.05). The plasma exchange group had a significantly higher treatment response rate than the conventional treatment group (P<0.05). There were no significant differences between the two groups in the total length of hospital stay and 3-month mortality rate (P>0.05).@*CONCLUSIONS@#Plasma exchange as an adjuvant therapy is effective for children with severe HPS. It can improve clinical symptoms and signs and some laboratory markers and shorten the length of stay in the PICU, and therefore, it may become an optional adjuvant therapy for children with severe HPS.
Subject(s)
Child , Humans , Intensive Care Units, Pediatric , Lymphohistiocytosis, Hemophagocytic/therapy , Plasma Exchange , Plasmapheresis , Prospective StudiesABSTRACT
Objective:To observe the short-term efficacy and safety of a new strategy of dexamethasone intravitreal implant (DEX) combined with ranibizumab in the treatment of retinal vein occlusion (RVO) secondary to macular edema (ME) (RVO-ME).Methods:A prospective clinical interventional study. From May 2020 to September 2021, 78 RVO-ME patients with 78 eyes diagnosed in the eye examination of Department of Ophthalmology of The First Affiliated Hospital of Anhui University of Science&Technology were included in the study. Among them, there were 35 males and 43 females, all with monocular disease. Branch retinal vein occlusion (BRVO) was found in 40 patients with 40 eyes; central retinal vein occlusion (CRVO) was found in 38 patients with 38 eyes. According to the treatment strategies, patients were randomly divided into DEX and ranibizumab combination therapy group (initial combination therapy group), DEX monotherapy group and ranibizumab monotherapy group, with 29 eyes, 26 eyes and 23 eyes respectively. Different types of RVO were divided into different treatment groups of BRVO and CRVO. Best corrected visual acuity (BCVA) and frequency domain optical coherence tomography were performed. The BCVA examination was carried out using the international standard visual acuity chart, which was converted into the logarithmic minimum angle of resolution (logMAR) visual acuity during statistics. There were no significant differences in logMAR BCVA ( χ2 =2.376) and central retinal thickness (CRT) ( F=0.052) among the three groups ( P>0.05). After treatment, the patients were followed up every month for 6 months. The changes of BCVA, CRT and the incidence of adverse reactions were observed during follow-up. One-way ANOVA and Kruskal-Wallis H test were used to compare the differences. Results:During the follow-up period, compared with the baseline, the BCVA of the eyes in the initial combination treatment group, DEX treatment group and ranibizumab treatment group were significantly improved ( Z=110.970, 90.359, 207.303), and CRT was significantly decreased ( F=107.172, 88.418, 61.040), the difference was statistically significant ( P<0.01). At 1, 2, 3, 4, 5, and 6 months after treatment, there were significant differences in the mean changes in BCVA between the initial combined treatment group, DEX treatment group, and ranibizumab treatment group ( χ2=34.522, 29.570, 14.199, 7.000, 6.434, 6.880; P<0.05); 1, 2, 3, and 6 months after treatment, the differences were statistically significant ( F=4.313, 7.520, 3.699, 3.152; P<0.05). The time required to improve BCVA by 0.1 logMAR units in the initial combination treatment group, DEX treatment group, and ranibizumab treatment group was 5.73 (3.21, 8.48), 9.97 (6.29, 18.78), and 20.00 (9.41, 37.89) d, respectively; The time required for CRT to drop to 300 μm was 24.31 (21.32, 26.15), 29.42 (25.65, 31.37), and 29.17 (25.28, 36.94) d, respectively. The BCVA improvement of 0.1 logMAR unit and the time required for CRT to decrease to 300 μm in the eyes of initial combined treatment group were shorter than those in the eyes of DEX treatment group and the ranibizumab treatment group, and the differences were statistically significant ( Z=-3.533, -4.445, -3.670, -4.030; P<0.01). Different BRVO treatment groups: 1, 2, 3, 5, and 6 months after treatment, the mean BCVA changes were significantly different ( χ 2=24.989, 21.652, 11.627, 7.054, 9.698; P<0.05); CRVO was different treatment group: 1 and 2 months after treatment, there were significant differences in mean BCVA changes ( χ 2=11.137, 9.746; P<0.05). Two months after treatment, there were significant differences in CRT changes between BRVO and CRVO groups with different treatment regimens ( F=3.960, 3.722; P<0.01). The time required to improve BCVA by 0.1 logMAR unit in the eyes of BRVO and CRVO combined treatment group was shorter than that in the eyes of BRVO, CRVO DEX treatment group and the BRVO, CRVO ranibizumab treatment group, and the differences were statistically significant (BRVO: Z=-2.687, -3.877; P<0.05; CRVO: Z=-2.437, -3.575; P<0.05). The time required for CRT to drop to 300 μm in the CRVO combined treatment group was significantly shorter than that in the CRVO DEX treatment group and the CRVO ranibizumab treatment group, and the difference was statistically significant ( F=6.910, P<0.010); there was no statistically significant difference between the different BRVO treatment groups ( F=1.786, P>0.05). The number of re-treated eyes in the initial combined treatment group and DEX treatment group was less than that in the ranibizumab treatment group, and the difference was statistically significant ( χ 2=18.330, 7.224; P<0.05). The retreatment interval of the eyes in the initial combined treatment group was significantly longer than that in the DEX treatment group and the ranibizumab treatment group, and the difference was statistically significant ( P <0.01). There was no significant difference in the incidence of intraocular hypertension among the initial combined treatment group, DEX treatment group and ranibizumab treatment group ( χ2=0.058, P>0.05). Conclusions:The new strategy of initial combination therapy with DEX and ranibizumab in the treatment of RVO-ME has a better short-term effect. Compared with the monotherapy group, the retreatment interval is shorter, the visual and anatomical benefits are faster, the efficacy lasts longer, and the safety is better.
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Objective:To observe the short-term efficacy and safety of a new strategy of dexamethasone intravitreal implant (DEX) combined with ranibizumab in the treatment of retinal vein occlusion (RVO) secondary to macular edema (ME) (RVO-ME).Methods:A prospective clinical interventional study. From May 2020 to September 2021, 78 RVO-ME patients with 78 eyes diagnosed in the eye examination of Department of Ophthalmology of The First Affiliated Hospital of Anhui University of Science&Technology were included in the study. Among them, there were 35 males and 43 females, all with monocular disease. Branch retinal vein occlusion (BRVO) was found in 40 patients with 40 eyes; central retinal vein occlusion (CRVO) was found in 38 patients with 38 eyes. According to the treatment strategies, patients were randomly divided into DEX and ranibizumab combination therapy group (initial combination therapy group), DEX monotherapy group and ranibizumab monotherapy group, with 29 eyes, 26 eyes and 23 eyes respectively. Different types of RVO were divided into different treatment groups of BRVO and CRVO. Best corrected visual acuity (BCVA) and frequency domain optical coherence tomography were performed. The BCVA examination was carried out using the international standard visual acuity chart, which was converted into the logarithmic minimum angle of resolution (logMAR) visual acuity during statistics. There were no significant differences in logMAR BCVA ( χ2 =2.376) and central retinal thickness (CRT) ( F=0.052) among the three groups ( P>0.05). After treatment, the patients were followed up every month for 6 months. The changes of BCVA, CRT and the incidence of adverse reactions were observed during follow-up. One-way ANOVA and Kruskal-Wallis H test were used to compare the differences. Results:During the follow-up period, compared with the baseline, the BCVA of the eyes in the initial combination treatment group, DEX treatment group and ranibizumab treatment group were significantly improved ( Z=110.970, 90.359, 207.303), and CRT was significantly decreased ( F=107.172, 88.418, 61.040), the difference was statistically significant ( P<0.01). At 1, 2, 3, 4, 5, and 6 months after treatment, there were significant differences in the mean changes in BCVA between the initial combined treatment group, DEX treatment group, and ranibizumab treatment group ( χ2=34.522, 29.570, 14.199, 7.000, 6.434, 6.880; P<0.05); 1, 2, 3, and 6 months after treatment, the differences were statistically significant ( F=4.313, 7.520, 3.699, 3.152; P<0.05). The time required to improve BCVA by 0.1 logMAR units in the initial combination treatment group, DEX treatment group, and ranibizumab treatment group was 5.73 (3.21, 8.48), 9.97 (6.29, 18.78), and 20.00 (9.41, 37.89) d, respectively; The time required for CRT to drop to 300 μm was 24.31 (21.32, 26.15), 29.42 (25.65, 31.37), and 29.17 (25.28, 36.94) d, respectively. The BCVA improvement of 0.1 logMAR unit and the time required for CRT to decrease to 300 μm in the eyes of initial combined treatment group were shorter than those in the eyes of DEX treatment group and the ranibizumab treatment group, and the differences were statistically significant ( Z=-3.533, -4.445, -3.670, -4.030; P<0.01). Different BRVO treatment groups: 1, 2, 3, 5, and 6 months after treatment, the mean BCVA changes were significantly different ( χ 2=24.989, 21.652, 11.627, 7.054, 9.698; P<0.05); CRVO was different treatment group: 1 and 2 months after treatment, there were significant differences in mean BCVA changes ( χ 2=11.137, 9.746; P<0.05). Two months after treatment, there were significant differences in CRT changes between BRVO and CRVO groups with different treatment regimens ( F=3.960, 3.722; P<0.01). The time required to improve BCVA by 0.1 logMAR unit in the eyes of BRVO and CRVO combined treatment group was shorter than that in the eyes of BRVO, CRVO DEX treatment group and the BRVO, CRVO ranibizumab treatment group, and the differences were statistically significant (BRVO: Z=-2.687, -3.877; P<0.05; CRVO: Z=-2.437, -3.575; P<0.05). The time required for CRT to drop to 300 μm in the CRVO combined treatment group was significantly shorter than that in the CRVO DEX treatment group and the CRVO ranibizumab treatment group, and the difference was statistically significant ( F=6.910, P<0.010); there was no statistically significant difference between the different BRVO treatment groups ( F=1.786, P>0.05). The number of re-treated eyes in the initial combined treatment group and DEX treatment group was less than that in the ranibizumab treatment group, and the difference was statistically significant ( χ 2=18.330, 7.224; P<0.05). The retreatment interval of the eyes in the initial combined treatment group was significantly longer than that in the DEX treatment group and the ranibizumab treatment group, and the difference was statistically significant ( P <0.01). There was no significant difference in the incidence of intraocular hypertension among the initial combined treatment group, DEX treatment group and ranibizumab treatment group ( χ2=0.058, P>0.05). Conclusions:The new strategy of initial combination therapy with DEX and ranibizumab in the treatment of RVO-ME has a better short-term effect. Compared with the monotherapy group, the retreatment interval is shorter, the visual and anatomical benefits are faster, the efficacy lasts longer, and the safety is better.
ABSTRACT
Objective:To investigate methods of molecular diagnosis and clinical features of 46, XY disorders of sexual development(DSD).Methods:A total of 206 cases of 46, XY DSD patients, who visited the Shanghai Ninth People′s Hospital, Shanghai Jiaotong University School of Medicine, from July 2009 to June 2021, underwent AA chip based on multiplex PCR and probe-capture-targeted next-generation sequencing. Clinical features of patients with genetic diagnosis were analyzed.Results:Among 206 patients, the diagnostic rate of patients with micropenis, hypospadias and cryptorchidism was the highest, up to 75.28%. Almost all patients had different degrees of undermasculinized external genitalia. The most frequent phenotype was micropenis with hypospadias(87.25%). Only one gene variant was detected in 81 patients(39.32%), multiple genetic variants were detected in 104 patients(50.49%), and no gene variant was identified in 21 patients(10.19%). 107 patients had definite genetic diagnosis, with a diagnostic rate of 51.94% by adding the pathogenic and likely pathogenic ratios following the American College of Medical Genetics and Genomics(ACMG) guidelines, including 40 patients of steroid 5α-reductase type 2(SRD5A2) variants(37.38%), 36 patients of androgen receptor(AR) variants(33.64%), 13 patients of steroidogenic factor 1(NR5A1) variants(16.82%), 6 patients of 17β-hydroxysteroid dehydrogenases 3(HSD17B3) variants(5.61%), 2 patients of 17α-hydroxylase/17, 20-lyase enzyme(CYP17A1), Wilms′ tumor 1(WT1) and GATA binding protein 4(GATA4) variants(1.87%), and one patient of luteinizing hormone receptor(LHCGR) variant(0.93%). Gynecomastia was found in 29 of 81 postpubertal patients, of which 25(86.21%) had AR variants.Conclusions:46, XY DSD presents complex clinical manifestations and molecular etiologies. Targeted nextgeneration sequencing has the advantages of high throughput, high efficiency and low cost, which has a high value especially in etiological diagnosis of 46, XY DSD with large genetic heterogeneity.