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Objective To observe the clinical efficacy of Yangxue Sanhan Tongmai Prescription(derived from the modification of Danggui Sini plus Wuzhuyu Shengjiang Decoction,i.e.,Danggui Sini Decoction with Euodiae Fructus and Zingiberis Rhizoma Recens added)for the treatment of endometriosis(EMS)of blood deficiency and cold coagulation type.Methods A total of 120 cases of EMS with blood deficiency and cold coagulation syndrome were randomly divided into the study group and the control group,with 60 cases in each group.The study group was treated with Yangxue Sanhan Tongmai Prescription,and the control group was treated with Shaofu Zhuyu Granules.Both groups were treated for a period of 3 months,and were followed up for one year after the completion of the treatment.The two groups were observed in the changes of the visual analogue scale(VAS)scores of menstrual abdominal pain,the grading scores of dysmenorrhea,non-menstrual pelvic pain,pain during sexual intercourse,pelvic pressure pain and sacral ligament tenderness,the size of ovarian endometriosis cysts,and the serum levels of carbohydrate antigen 125(CA125),vascular endothelial growth factor(VEGF),soluble intercellular adhesion molecule 1(SICAM-1),matrix metalloproteinase 9(MMP-9)and tissue inhibitor of metalloproteinase 2(TIMP-2).After treatment,the clinical efficacy and safety,recurrence and pregnancy in the two groups were evaluated.Results(1)In the course of the trial,3 cases fell off in the study group and 5 cases fell off in the control group,and a total of 112 patients were eventually included in the statistical analysis,including 57 cases in the study group and 55 cases in the control group.(2)After 3 months of treatment,the total effective rate in the study group was 92.98%(53/57)and that in the control group was 85.45%(47/55),and the intergroup comparison showed that the efficacy of the study group was significantly superior to that of the control group(P＜0.05).(3)After treatment,VAS scores of menstrual abdominal pain and the grading scores of dysmenorrhea,non-menstrual pelvic pain,pain during sexual intercourse,pelvic pressure pain and sacral ligament tenderness in the two groups were significantly reduced compared with those before treatment(P＜0.05),and the reduction in the study group was significantly superior to that in the control group(P＜0.05).(4)After treatment,the ovarian endometriosis cysts of the two groups were slightly reduced,but the intragroup pre-and post-treatment differences and the intergroup post-treatment differences were not statistically significant(P＞0.05).(5)After treatment,the levels of serum CA125,VEGF,SICAM-1 and MMP-9 were decreased and the serum TIMP-2 level was increased in both groups compared with those before treatment(P＜0.05).And the decrease of serum CA125,VEGF,SICAM-1 and MMP-9 as well as the increase of serum TIMP-2 in the study group were significantly superior to those in the control group(P＜0.05).(6)The results of one-year follow-up showed that the recurrence rate of the study group was 30.19%(16/53),which was significantly lower than that of the control group(68.09%,32/47),and the difference was statistically significant between the two groups(P＜0.05).In the study group,there were 21 patients having the fertility desire,and then 14 cases of them were pregnant after treatment,with a pregnancy rate of 66.67%(14/21);in the control group,there were 20 cases having fertility desire,and then 4 cases of them were pregnant after treatment,with a pregnancy rate of 20.00%(4/20).The intergroup comparison showed that the pregnancy rate of the study group was significantly higher than that of the control group,and the difference was statistically significant(P＜0.05).(7)During the treatment period,there were no obvious adverse reactions in the two groups,and there were no abnormal changes in the safety indexes of blood,urine,and stool routine test,electrocardiogram,and liver and kidney function.Conclusion Yangxue Sanhan Tongmai Prescription exerts certain effect in treating patients with endometriosis of blood deficiency and cold coagulation type,which can significantly alleviate various pain symptoms,improve pregnancy outcomes,and effectively regulate the levels of serum CA125,VEGF,SICAM-1,MMP-9 and TIMP-2 of the patients.
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Objective To investigate the therapeutic effects and mechanisms of Maxing Shigan Decoction on cough variant asthma(CVA)rats.Methods Sixty rats were randomly divided into normal group,model group,low and high dose groups of Maxing Shigan Decoction,and high-dose of Maxing Shigan Decoction + signal transducer and activator of transcription 3(STAT3)activator Colivelin(Col)group,12 rats in each group.Except for the normal group,the CVA model was constructed by intraperitoneal injection of ovalbumin combined with moxa fumigation in all other groups of rats.After the corresponding treatment,the rats were observed for signs and cough counts,airway resistance(RE)was detected by pulmonary function meter,eosinophils(EOS)were counted by Diff-Quik staining,histopathological features of the lungs and bronchial tubes were observed by hematoxylin-eosin(HE)staining method,and the lung tissues were detected by enzyme-linked immunosorbent assay(ELISA)for monocyte chemotactic protein 1(MCP-1),and tumor necrosis factor α(TNF-α),and the protein expression levels of interleukin 6(IL-6),STAT3,and transient receptor potential vanilloid-1 channel(TRPV1)were detected by Western Blot.Results Compared with the normal group,rats in the model group showed obvious asthma symptoms,severe inflammatory cell infiltration was seen in the lung tissue,bronchial epithelial cell necrosis,ciliated adhesion,mucus,and RE,EOS number,MCP-1 and TNF-α contents,and protein expression levels of IL-6,STAT3,TRPV1 were elevated(P＜0.05);compared with the model group,rats in the low-and high-dose groups of Maxing Shigan Decoction showed significant improvement in asthma symptoms,reduction in lung and bronchial injury,and dose-dependent reduction in RE,EOS number,MCP-1 and TNF-α contents,and protein expression levels of IL-6,STAT3,and TRPV1(P＜0.05);compared with the high-dose group of Maxing Shigan Decoction,the rats in the high-dose Maxing Shigan Decoction+Col group showed increased asthma,increased lung and bronchial injury,and increased RE,EOS number,MCP-1 and TNF-α contents,and protein expression levels of IL-6,STAT3,and TRPV1(P＜0.05).Conclusion Maxing Shigan Decoction can effectively improve cough variant asthma in rats,and its mechanism is related to the inhibition of IL-6/STAT3 signaling pathway and the high expression of TRPV1.
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Objective To summarize the epidemiological and clinical features of infectious diseases of the central nervous system(CNS)by a single-center analysis.Methods A retrospective analysis was conducted on the data of 1247 cases of CNS infectious diseases diagnosed and treated in the First Medical Center of PLA General Hospital from 2001 to 2020.Results The data for this group of CNS infectious diseases by disease type in descending order of number of cases were viruses 743(59.6％),Mycobacterium tuberculosis 249(20.0％),other bacteria 150(12.0％),fungi 68(5.5％),parasites 18(1.4％),Treponema pallidum 18(1.4％)and rickettsia 1(0.1％).The number of cases increased by 177 cases(33.1％)in the latter 10 years compared to the previous 10 years(P<0.05).No significant difference in seasonal distribution pattern of data between disease types(P>0.05).Male to female ratio is 1.87︰1,mostly under 60 years of age.Viruses are more likely to infect students,most often at university/college level and above,farmers are overrepresented among bacteria and Mycobacterium tuberculosis,and more infections of Treponema pallidum in workers.CNS infectious diseases are characterized by fever,headache and signs of meningeal irritation,with the adductor nerve being the more commonly involved cranial nerve.Matagenomic next-generation sequencing improves clinical diagnostic capabilities.The median hospital days for CNS infectious diseases are 18.00(11.00,27.00)and median hospital costs are ￥29,500(￥16,000,￥59,200).The mortality rate from CNS infectious diseases is 1.6％.Conclusions The incidence of CNS infectious diseases is increasing last ten years,with complex clinical presentation,severe symptoms and poor prognosis.Early and accurate diagnosis and standardized clinical treatment can significantly reduce the morbidity and mortality rate and ease the burden of disease.
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BACKGROUND:The increase in multi-drug resistant bacterial infections has become a major problem in modern healthcare due to the development of bacterial resistance to antibiotics and the development of new antibacterial alternative drug materials is of great importance. OBJECTIVE:To synthesize and perform a series of characterization of a CeO2 nanoenzyme to investigate its biocompatibility and antibacterial properties against Escherichia coli. METHODS:CeO2 nanoenzymes were synthesized using a hydrothermal method.The morphology,product composition,and chemical composition were analyzed using characterization methods such as X-ray diffraction,X-ray photoelectron spectroscopy,Fourier infrared analysis,Raman spectroscopy,scanning electron microscopy,and transmission electron microscopy.The peroxide-mimetic enzyme activity of CeO2 nanoenzymes was characterized using TMB color development assay.The toxic effect of CeO2 nanoenzymes at different concentrations(10,25,and 50 μg/mL)on mouse fibroblast L929 cells was evaluated using the CCK-8 assay.The antibacterial properties of CeO2 nanoenzymes against Escherichia coli under different conditions were evaluated using the plate coating method.Changes in intra-bacterial reactive oxygen species after treatment with different conditions were detected using a reactive oxygen species detection kit. RESULTS AND CONCLUSION:(1)The morphology of the synthesized CeO2 nanoparticles was rod-shaped,with Ce3+ accounting for 29.87%of the total Ce3+/Ce4+ and an average grain size of 7.4 nm.In a slightly acidic environment containing TMB and pH=5.5,CeO2 nanoenzymes mixed with H2O2 showed excellent peroxidase activity,but did not show peroxidase simulated activity at pH=7.4.(2)There was no statistically significant difference in the toxic effects of CeO2 nanoparticles at various mass concentrations on mouse fibroblast L929 cells.(3)In a slightly acidic environment at pH 5.5,Escherichia coli was inhibited to a certain extent in the presence of CeO2 nanoenzyme alone at a concentration of 10 μg/mL,with a decrease in CFU results of about 0.5 log(P＜0.01);in a slightly acidic environment containing 50 μmol/L H2O2,CeO2 nanoenzyme showed excellent antibacterial effects against Escherichia coli,with a decrease in Escherichia coli CFU results of by about 1.5 log(P＜0.001).After CeO2 nanoenzymes interacted with Escherichia coli,the level of reactive oxygen species in Escherichia coli increased(P＜0.05);after CeO2 nanoenzymes interacted with Escherichia coli together with H2O2,the level of reactive oxygen species in Escherichia coli increased significantly(P＜0.001).(4)The results show that the CeO2 nanoenzymes have good biocompatibility,are inherently antibacterial,and can exhibit peroxidase activity in a slightly acidic environment containing low concentrations of H2O2,and generate reactive oxygen species to kill bacteria,thus showing excellent antibacterial effects.
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BACKGROUND:There is an internal relationship between hyperhomocysteinemia and vascular calcification.However,the pathogenesis of hyperhomocysteinemia promoting vascular calcification is still unclear. OBJECTIVE:To investigate the role of bone morphogenetic protein-2 in hyperhomocysteinemia-induced vascular calcification. METHODS:Human carotid wax samples were divided into a calcified group(n=29)and a non-calcified group(n=13)according to the presence or absence of calcified plaque.Sixteen ApoE-/-mice were randomly divided into a control group and a hyperhomocysteinemia group,with 8 mice in each group.Bone morphogenetic protein-2 vector was used to transfect rat thoracic artery smooth muscle A7r5 cells,and gradient concentration of homocysteine(50,100,200,and 400 μmol/L)was utilized to treat A7r5 cells.Calcification was detected by alizarin red staining and hematoxylin-eosin staining.The interaction of bone morphogenetic protein 2 with Runt-related transcription factor 2 was detected by immunofluorescence,and the expressions of bone morphogenetic protein 2,Runt-related transcription factor 2,and α-smooth muscle actin were detected by immunohistochemistry and western blot assay. RESULTS AND CONCLUSION:(1)Human carotid artery tissue staining revealed that compared with the non-calcification group,inflammatory cells increased and calcification positive rate increased in the calcification group(P<0.05).Compared with the non-calcification group,the expressions of bone morphogenetic protein-2 and Runt-related transcription factor 2 were up-regulated,and the expression of α-smooth muscle actin was decreased in the calcification group(all P<0.05).(2)The staining of mouse arterial specimens exhibited that,the positive rate of calcified area in the hyperhomocysteinemia group was significantly higher than that in the control group(P<0.05);serum homocysteine level in the hyperhomocysteinemia group was significantly higher than that in the control group(P<0.05).Compared with the control group,the expressions of bone morphogenetic protein-2 and Runt-related transcription factor 2 were up-regulated,and the expression of α-smooth muscle actin was decreased in the hyperhomocysteinemia group(all P<0.05).(3)A7r5 cell culture analysis demonstrated that with the increase of homocysteine concentration gradient,the degree of calcification,the content of bone morphogenetic protein-2 and Runt-related transcription factor 2 protein in A7r5 cells increased(P<0.05),and the content of α-smooth muscle actin protein decreased(P<0.05).(4)The A7r5 cell culture analysis of overexpressed bone morphogenetic protein 2 showed that the calcification degree of the overexpressed bone morphogenetic protein 2 group was increased compared with the corresponding control group,the β-sodium glycerophosphate group,and the homocysteine group.RUNt-related transcription factor 2 expression up-regulated(P<0.05)and α-smooth muscle actin expression down-regulated(P<0.05).(5)The expression of bone morphogenetic protein 2 increased in A7r5 cells cultured with homocysteine in calcified medium,and the expression of Runt-related transcription factor 2 increased with the increase of bone morphogenetic protein 2 expression.(6)The results confirm that bone morphogenetic protein-2 is a key target gene in the regulation of smooth muscle cell phenotypic transformation resulting in vascular calcification by hyperhomocysteinemia.Targeted regulation of bone morphogenetic protein-2 reduces hyperhomocysteinemia-induced vascular calcification.
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BACKGROUND:Hyperhomocysteinemia is closely related to the function of islet β cells,but its specific molecular mechanism is not fully understood. OBJECTIVE:To investigate the role of N6 methyltransferase-like 3(METTL3)in homocysteine(Hcy)-induced autophagy of mouse islet β cells. METHODS:The 3rd and 4th generation mouse islet β cells were taken for the experiment.(1)Cell modeling and grouping:cells in control group were not treated with Hcy,while those in homocysteine group were treated with 100 μmol/L Hcy for 48 hours.(2)The mouse islet β-cells were transfected with the plasmids overexpressing Ad-METTL3 and si-METTL3 according to the instructions of LipofectamineTM 2000.Three different interfering fragments were designed,and the one with the best interfering efficiency was verified and screened by PCR.(3)After transfection,the cells were divided into control group,Hcy group,Ad-NC(negative control)+Hcy group,Ad-METTL3+Hcy group,si-NC(negative control)+Hcy group and si-METTL3+Hcy group.(4)qRT-PCR and western blot were used to detect the expression levels of METTL3 and autophagy-related proteins LC3Ⅱ/Ⅰ and p62 in cells.Insulin level was determined by ELISA to evaluate insulin secretion capacity of islet cells.Autophagy-related proteins and insulin level were detected after overexpression and interference with METTL3. RESULTS AND CONCLUSION:Compared with the control group,the expression level of LC3Ⅱ/Ⅰ was increased(P＜0.05),the expression of p62 was significantly reduced(P＜0.05),and the insulin secretion capacity was significantly decreased(P＜0.05)in the Hcy group.Compared with the control group,the protein and mRNA levels of METTL3 were reduced in the Hcy group(P＜0.05).After METTL3 silencing in islet β cells,Hcy further upregulated the expression of LC3Ⅱ/Ⅰ(P＜0.05),significantly dowregulated the expression of p62(P＜0.05),and increased the insulin level(P＜0.05).After overexpression of METTL3,Hcy significantly decreased the LC3Ⅱ/Ⅰ expression and increased the p62 expression in islet β cells(P＜0.05).To conclude,METTL3 is involved in the Hcy-induced autophagy regulation of islet β cells and plays a role in the regulation of insulin secretion.
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Diabetic retinopathy(DR)is a common complication of diabetes.Sodium-glucose cotransporter 2(SGLT-2)inhibitors are widely used in diabetic patients as hypoglycemic drugs and also play a role in the prevention and treatment of DR.At present,there has been no systematic study on the clinical treatment of DR by SGLT-2 inhibitors.This paper re-views the research progress of SGLT-2 inhibitors in the treatment of DR,in order to provide more ideas for the clinical treatment of DR.
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Objective:To investigate the effect of tripartite motif-containing protein 59 (TRIM59) on glucose metabolism in macrophages and its role in regulating hypoxia-inducible factor-1α (HIF-1α)/IL-10 axis in macrophages under inflammatory conditions.Methods:The differentially expressed genes between macrophages with high expression of TRIM59 and control cells transfected with empty TRIM59 plasmid were analyzed by GO and KEGG. The expression of HIF-1α by RAW264.7 macrophages with high expression of TRIM59 was detected at different time points after lipopolysaccharide (LPS) stimulation by RT-qPCR and Western blot. Bone marrow was isolated from TRIM59-cKO and TRIM59 flox/flox mice and induced to differentiate into bone marrow-derived macrophages (BMDMs). These BMDMs were stimulated with LPS and the supernatants of cell culture were collected at 3, 6, 12 and 24 h after stimulation to detect IL-10 level by ELISA. In addition, mouse models of cecal ligation and puncture (CLP) were established, and bronchoalveolar lavage fluid (BALF) samples were collected at the same time points to detect IL-10 level by ELISA. Histopathological changes in lung tissues were observed after HE staining. Results:There was a significant change in glucose metabolism-related genes in macrophages with high expression of TRIM59, and the content of lactic acid increased significantly. Compared with the control group, the expression of HIF-1α at mRNA level in BMDMs from TRIM59-cKO mice decreased after LPS stimulation ( P<0.05); the level of IL-10 increased at 3 h and 24 h in the TRIM59-cKO group, but there was no significant difference in IL-10 level at 6 h or 12 h between the two groups. In the TRIM59-cKO mouse model of CLP, the levels of IL-10 in the BALF samples increased with time, but decreased at 24 h. The level of IL-10 was higher in the TRIM59-cKO mouse model group than that in the control group at each time point ( P<0.05 or P<0.01). Conclusions:TRIM59 can inhibit inflammation and lung injury by decreasing HIF-1α-mediated lactate secretion and IL-10 expression in macrophages. This study provides a new idea for developing novel anti-sepsis drugs based on TRIM59.
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Objective To comprehensively analyze the reported preparation methods for animal models of perimenopausal syndrome (PS), to compare the advantages and disadvantages of various preparation elements and detection indexes, so as to provide useful references for the optimization of the relevant animal models as well as the standardization of their application in the efficacy evaluation of new drugs.MethodsIn this paper, literature research methods were applied using "perimenopausal syndrome" as the subject term. The publication period of the literature was limited to January 2016 to February 2023. Relevant literature on the preparation of PS animal models was retrieved from databases such as China National Knowledge Infrastructure, Wanfang database, and PubMed. After screening the experimental literature that met the inclusion and exclusion criteria, detailed information on experimental animal strains, modeling methods, duration of drug administration, positive drugs, detection indexes and other relevant information were collected. After the above information was standardized, the PS animal model database was established using Excel 2010 software. The model preparation elements and evaluation indexes were summarized systematically, and the statistical results were processed and analyzed using Excel 2010 software.Results A total of 247 articles were screened. SD rats (164 times, 65.86%) and Wistar rats (35 times, 14.06%) were often used to prepare PS animal models. Bilateral ovariectomy (139 times, 53.87%) and natural aging (43 times, 16.80%) were chosen as modeling methods. The ages of rats used for modeling ranged from 7 weeks to 18 months, with 3-month-old rats (22 times, 21.78%) being the most common. The detection indexes were comprehensively evaluated from multiple perspectives, including serum biochemistry, vaginal exfoliated cell smear, histomorphology, general observation, behavioral observation, and organ tissue protein immunoblotting. Western medical evaluation indexes were commonly used to test the successful preparation of models, with vaginal exfoliated cell smears being the most frequently used method (125 times, 85.04%). A model was considered successfully prepared when estrous cycle disorder or irregularity was observed. Some literature also determined modeling success by detecting a significant decrease in serum estradiol levels (5 times, 3.04%). Traditional Chinese medicine (TCM) syndrome evaluation often used a combination of Chinese and Western medical evaluation indexes for comprehensive evaluation, with researchers determining the TCM syndrome through vaginal exfoliated cell smears supplemented by general observation (3 times, 2.04%).Conclusion There are many methods for preparing PS animal models, but there are still significant differences in the selection of animal species, age, criteria for successful modeling, and TCM syndrome evaluation in the related literature.
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Cyclosporine A, a cyclic polypeptide, exhibits potent immunosuppressive activity and exerts its effects through various mechanisms including immunosuppression, anti-inflammatory, inhibition of apoptosis, promotion of epithelial healing and goblet cell function recovery, enhancement of tear secretion, and close association with ocular surface disease repair. Owing to its significant efficacy, inhibition of disease recurrence and few side effects, the clinical application of cyclosporine A in the management of ocular surface diseases, including dry eye, corneal graft rejection following penetrating keratoplasty, vernal keratoconjunctivitis, noninfective keratitis and herpes simplex virus keratitis, has witnessed a substantial rise in recent years. Nevertheless, variations exist in the management of ocular surface inflammatory diseases when utilizing distinct concentrations and dosage forms of cyclosporine A. Therefore, the paper provides an overview of impacts of cyclosporine A on ocular surface diseases.
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ObjectiveTo investigate the role of traditional Chinese medicine （TCM） constitution in the progression of abnormal glucose metabolism among community population. MethodsA total of 393 community residents who participated in community diabetes screening from 2019 to 2021 and had complete physical examination data at baseline and at the 2nd year follow-up were selected. According to the results of glucose tolerance tests， community residents were divided into the abnormal glucose metabolism progression group and non-progression group， and were matched at the ratio of 1∶2 using the propensity score matching. The influencing factors related to diabetes at baseline were collected for both groups. The traditional Chinese medicine constitution was determined among population in two groups. The differences of influencing factors and traditional Chinese medicine constitution between the two groups were compared. Logistic regression analysis was used to analyze the risk factors for the progression of abnormal glucose metabolism. ResultsFinally， 131 patients were included in the progression group and 262 patients in the non-progression group. Compared to the non-progression group， the progression group had significantly higher proportion of hyperlipidemia history ， hyperglycemia history， phlegm-dampness constitution， and blood stasis constitution （P＜0.05 or P＜0.01）. Univariate logistic regression analysis revealed that the history of hyperlipidemia （P=0.011）， history of hyperglycemia （P＜0.001）， the family history of diabetes （P＜0.001）， yin-deficiency constitution （P=0.047）， phlegm-dampness constitution （P=0.011） and blood-stasis constitution （P=0.008） were risk factors for the progression of abnormal glucose metabolism. Multivariate logistic regression analysis indicated that the history of hyperglycemia （P＜0.001）， yin-deficiency constitution （P=0.026） and blood-stasis constitution （P=0.032） were independent risk factors for the progression of abnormal glucose metabolism. ConclusionThe history of hyperglycemia， yin-deficiency constitution and blood-stasis constitution may be the risk factors for the progression of abnormal glucose metabolism.
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AIM: To evaluate the performance of three distinct large language models(LLM), including GPT-3.5, GPT-4, and PaLM2, in responding to queries within the field of ophthalmology, and to compare their performance with three different levels of medical professionals: medical undergraduates, master of medicine, and attending physicians.METHODS: A total of 100 ophthalmic multiple-choice tests, which covered ophthalmic basic knowledge, clinical knowledge, ophthalmic examination and diagnostic methods, and treatment for ocular disease, were conducted on three different kinds of LLM and three different levels of medical professionals(9 undergraduates, 6 postgraduates and 3 attending physicians), respectively. The performance of LLM was comprehensively evaluated from the aspects of mean scores, consistency and confidence of response, and it was compared with human.RESULTS: Notably, each LLM surpassed the average performance of undergraduate medical students(GPT-4:56, GPT-3.5:42, PaLM2:47, undergraduate students:40). Specifically, performance of GPT-3.5 and PaLM2 was slightly lower than those of master's students(51), while GPT-4 exhibited a performance comparable to attending physicians(62). Furthermore, GPT-4 showed significantly higher response consistency and self-confidence compared with GPT-3.5 and PaLM2.CONCLUSION: LLM represented by GPT-4 performs well in the field of ophthalmology, and the LLM model can provide clinical decision-making and teaching aids for clinicians and medical education.
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The aim of this study was to investigate the virulence determinants and genetic diversity of foodborne Yersinia enterocolitica from Wenzhou.A total of 71 strains of Yersinia enterocolitica were isolated from food and foodborne diarrhea ca-ses in Wenzhou,and their biotypes,serotypes,and drug resistance were analyzed.On the basis of whole genome sequencing,we assessed virulence gene profiles,and performed multilocus sequence typing(MLST)and core gene multilocus sequence typ-ing(cgMLST).A total of 94.4％(67/71)of isolates belonged to biotype 1A,and the highest proportion had serotype lA/O∶5(29.6％,21/71).The sensitivity rates of the isolates to 14 antibiotics exceeded 95.8％.A total of 16 categories and 126 viru-lence genes were identified,with two strains carrying the pYV plasmid and chromosome-related virulence genes.ST3(31.6％,12/38)was the most widespread MLST type,and cgMLST analysis revealed no dense clusters of genotypes except for strains sharing the same ST.In conclusion,pathogenic strains were identified from foodborne Yersinia enterocolitica in Wenzhou and were found to exhibit high genetic polymorphism.Enhanced regulatory supervision is essential to prevent the outbreak of food-borne diseases caused by Yersinia enterocolitica.
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【Objective】 To analyze the cost and effectiveness of different HIV screening strategies based on multi-center HIV residual risk study, so as to provide reference for blood centers to adopt appropriate HIV testing strategies. 【Methods】 According to the HIV screening and confirmation of blood donors in three blood centers in Anhui Province, the residual risk of different HIV screening strategies was estimated. A decision tree model was established to analyze the cost-effectiveness differences of three different screening strategies under current domestic policies. 【Results】 The residual risk of anti-HIV-1 +2 ELISA, HIV Ag/Ab1+2 ELISA and ELISA+NAT were 1.17×10-6,0.84×10-6 and 0.59×10-6, respectively. According to decision tree model analysis, HIV Ag/Ab1+2 ELISA had a cost-effectiveness advantage over anti-HIV 1+2 ELISA when there was no NAT, but the advantage of HIV Ag/Ab1+2 ELISA disappeared when there was one NAT. The cost of HIV reagents, the cost of HIV treatment and the cost of false positive discarding were sensitive factors of the model. 【Conclusion】 In this area, one anti-HIV 1+2 ELISA combined with one NAT has a cost-effectiveness advantage. Blood centers need to confirm and evaluate the ELISA reagents used before conducting HIV screening. Under the premise of ensuring sensitivity, reagent cost and reagent false positive rate are the key factors.
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The lungs are one of the most common extra-articular organs involved in rheumatoid arthritis (RA), which is reported to occur in up to 60% to 80% of RA patients. Respiratory complications are the second leading cause of death due to RA. Although there is a wide spectrum of RA-associated respiratory diseases, interstitial lung disease is the most common manifestation and it impacts the prognosis of RA. There has been progress in understanding the management and progression of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and RA-associated respiratory diseases recently, for example, opportunistic pulmonary infectious diseases and toxicity from RA therapies. From a chest physicians' perspective, we will update the diagnosis and treatment of RA-associated ILD, methotrexate-associated lung disease, and the complication of Pneumocystis jiroveci pneumonia in RA in this review.
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Humans , Arthritis, Rheumatoid/complications , Methotrexate/therapeutic use , Lung Diseases, Interstitial/complications , Prognosis , LungABSTRACT
OBJECTIVE@#To explore the prevalence and clinical manifestations of ring chromosomes among children featuring abnormal development.@*METHODS@#From January 2015 to August 2021, 7574 children referred for abnormal development were selected, and their peripheral blood samples were subjected to G-banded chromosomal karyotyping analysis.@*RESULTS@#Twelve cases of ring chromosomes were detected, which have yielded a prevalence of 0.16% and included 1 r(6), 2 r(9), 1 r(13), 1 r(14), 2 r(15), 1 r(21) and 3 r(X). The children had various clinical manifestations including growth and mental retardation, limb malformation, and congenital heart disease. For two children with r(9) and two with r(15) with similar breakpoints, one child with r(9) and one with r(15) only had growth retardation, whilst another with r(9) and another with r(15) also had peculiar facies and complex congenital heart disease. The r(X) has featured some manifestations of Turner syndrome.@*CONCLUSION@#Ring chromosomes are among the common causes for severe growth and mental retardation in children with diverse clinical phenotypes. Clinicians should pay attention to those with developmental anomalies and use chromosomal analysis to elucidate their genetic etiology.
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Humans , Ring Chromosomes , Intellectual Disability/genetics , Turner Syndrome/genetics , Phenotype , Heart Defects, Congenital/geneticsABSTRACT
Objective: To clarify the phenotypes of the newborns with SLC26A4 single-allele mutation in deafness genetic screening and second variant; to analyze the SLC26A4 genotype and hearing phenotype. Methods: 850 newborns born in Beijing from April 2015 to December 2019 were included and there were 468 males and 382 females. They received genetic deafness screening for 9 or 15 variants, with the result of SLC26A4 single-allele mutation. Firstly, three step deafness gene sequencing was adopted in this work, i.e., the first step was "SLC26A4 gene whole exons and splice sites" sequencing; the second step was "SLC26A4 gene promoter, FOXI1 gene and KCNJ10 gene whole exons" sequencing; and the third step was detection for "SLC26A4 gene copy number variation". Secondly, we collected the results of newborn hearing screening for all patients with the second mutation found in the three step test, and conducted audiological examinations, such as acoustic immittance, auditory brainstem response and auditory steady state response. Thirdly, for novel/VUS mutations, we searched the international deafness gene database or software, such as DVD, ClinVar and Mutation Taster, to predict the pathogenicity of mutations according to the ACMG guideline. Lastly, we analyzed the relationship between genotype and phenotype of newborns with SLC26A4 single allele mutation. Results: Among 850 cases, the median age of diagnosis was 4 months. In the first step, 850 cases were sequenced. A total of 32 cases (3.76%, 32/850) of a second variants were detected, including 18 cases (2.12%, 18/850) with identified pathogenic variants; 832 cases were sequenced and 8 cases of KCNJ10 gene missense variants were detected among the second step. No missense mutations in the FOXI1 gene and abnormal SLC26A4 gene promoter were detected; the third step sequencing results were all negative. Genotypes and hearing phenotypes included 18 cases combined with the second clear pathogenic variant, 16 cases (16/18) referred newborn hearing screening and 2 cases (2/18) passed in both ears; degree of hearing loss consisted of 18 profound ears (18/36), 13 severe ears (13/36) and 5 moderate ears (5/36); audiogram patterns comprised 17 high frequency drop ears (17/36), 14 flat ears (14/36), 3 undistinguished ears (3/36), and 2 U shaped ears (2/36); 11 cases underwent imaging examination, all of which were bilateral enlarged vestibular aqueduct. As for 22 cases of other genotypes, all passed neonatal hearing screening and the hearing diagnosis was normal, including 9 cases with VUS or possibly novel benign variants, 8 cases with KCNJ10 double gene heterozygous variants, and 5 cases with double heterozygous variants. Conclusions: The probability of individuals with SLC26A4 single-allele variant who merge with a second pathogenic variant is 2.12%, all of which are SNV, which can provide scientific basis for the genetic diagnosis and genetic counseling of SLC26A4 variants. Those who have merged with second pathogenic variant are all diagnosed with sensorineural hearing loss. Patients with KCNJ10 gene mutations do not manifest hearing loss during the infancy, suggesting the need for further follow-up.
Subject(s)
Female , Humans , Male , Infant, Newborn , Alleles , Deafness/genetics , DNA Copy Number Variations , Forkhead Transcription Factors/genetics , Genotype , Hearing Loss/genetics , Hearing Loss, Sensorineural/genetics , Mutation , Phenotype , Sulfate Transporters/genetics , Vestibular Aqueduct , Potassium Channels, Inwardly Rectifying/geneticsABSTRACT
OBJECTIVE@#To establish the finite element model of varus-type ankle arthritis and to implement the finite element mechanical analysis of different correction models for tibial anterior surface angle (TAS) in supramalleolar osteotomy.@*METHODS@#A female patient with left varus-type ankle arthritis (Takakura stage Ⅱ, TAS 78°) was taken as the study object. Based on the CT data, the three-dimensional model of varus-type ankle arthritis (TAS 78°) and different TAS correction models [normal (TAS 89°), 5° valgus (TAS 94°), and 10° valgus (TAS 99°)] were created by software Mimics 21.0, Geomagic Wrap 2021, Solidworks 2017, and Workbench 17.0. The 290 N vertical downward force was applied to the upper surface of the tibia and 60 N vertical downward force to the upper surface of the fibula. Von Mises stress distribution and stress peak were calculated.@*RESULTS@#The finite element model of normal TAS was basically consistent with biomechanics of the foot. According to biomechanical analysis, the maximum stress of the varus model appeared in the medial tibiotalar joint surface and the medial part of the top tibiotalar joint surface. The stress distribution of talofibular joint surface and the lateral part of the top tibiotalar joint surface were uniform. In the normal model, the stress distributions of the talofibular joint surface and the tibiotalar joint surface were uniform, and no obvious stress concentration was observed. The maximum stress in the 5° valgus model appeared at the posterior part of the talofibular joint surface and the lateral part of the top tibiotalar joint surface. The stress distribution of medial tibiotalar joint surface was uniform. The maximum stress of the 10° valgus model appeared at the posterior part of the talofibular joint surface and the lateral part of the top tibiotalar joint surface. The stress on the medial tibiotalar joint surface increased.@*CONCLUSION@#With the increase of valgus, the stress of ankle joint gradually shift outwards, and the stress concentration tends to appear. There was no obvious obstruction of fibula with 10° TAS correction. However, when TAS correction exceeds 10° and continues to increase, the obstruction effect of fibula becomes increasingly significant.
Subject(s)
Humans , Female , Tibia/surgery , Finite Element Analysis , Ankle , Arthritis , Fibula/surgery , Ankle Joint/surgeryABSTRACT
Glucocorticoid-induced osteoporosis (GIOP) is a skeletal disease characterized by decreased bone strength and increased fracture risk associated with long-term glucocorticoid use. GIOP is the most common secondary osteoporosis that critically affects the quality of life of patients. Currently, the incidence of GIOP in China remains high, with insufficient awareness and lack of prevention and treatment norms. Therefore, the Chinese Rheumatology Association has established this standard based on domestic and international experience, with the aim of raising awareness of prevention and treatment among clinicians, guiding the standardized diagnosis and treatment of this disease, and improving the overall prognosis of patients with GIOP.
Subject(s)
Humans , Glucocorticoids/adverse effects , Quality of Life , Osteoporosis/therapy , Incidence , Rheumatology , Bone DensityABSTRACT
Objective: To investigate the misdiagnosis of area postrema syndrome (APS) manifesting as intractable nausea, vomiting and hiccups in neuromyelitis optic spectrum disease (NMOSD) and reduce the risk of misdiagnosis. Methods: We retrospectively analyzed data from NMOSD patients attending the Department of Neurology at the First Medical Center of PLA General Hospital between January 2019 and July 2021. SPSS25.0 was then used to analyze the manifestations, misdiagnosis, and mistreatment of APS. Results: A total of 207 patients with NMOSD were included, including 21 males and 186 females. The mean age of onset was 39±15 years (range: 5-72 years). The proportion of patients who were positive for serum aquaporin 4 antibody was 82.6% (171/207). In total, 35.7% (74/207) of the NMOSD patients experienced APS during the disease course; of these patients, 70.3% (52/74) had APS as the first symptom and 29.7% (22/74) had APS as a secondary symptom. The misdiagnosis rates for these conditions were 90.4% (47/52) and 50.0% (11/22), respectively. As the first symptom, 19.2% (10/52) of patients during APS presented only with intractable nausea, vomiting and hiccups; 80.8% (42/52) of patients experienced other neurological symptoms. The Departments of Gastroenterology and General Medicine were the departments that most frequently made the first diagnosis of APS, accounting for 54.1% and 17.6% of patients, respectively. The most common misdiagnoses related to diseases of the digestive system and the median duration of misdiagnosis was 37 days. Conclusions: APS is a common symptom of NMOSD and is associated with a high rate of misdiagnosis. Other concomitant symptoms often occur with APS. Gaining an increased awareness of this disease/syndrome, obtaining a detailed patient history, and performing physical examinations are essential if we are to reduce and avoid misdiagnosis.