Orogenital ulcers and the Behcet’s disease

Behcet’s’s disease is a systemic vasculitis involving small to large veins and arteries. It is a sporadic disease, mostly prevalent among the ancestors of the silk route. It is characterized by recurrent oral ulcers, genital ulcers, and uveitis. It also can manifest as skin, vascular, gastrointestinal, neurological, cardiac, and renal involvement. Though overall mortality is around 5%, delay in diagnosis and treatment may lead to significant morbidity. Cardiovascular and pulmonary arterial aneurysms are dreadful complications of this disease. Being uncommon in south India it is liable to be wrongly diagnosed and treated. Delay in the diagnosis and treatment may lead to severe complications. Here we present a case of Behcet’s disease which was managed at primary health care inadequately. We also demonstrated a quick response to steroids which are the mainstay of treatment. In this case presentation we illustrated pre and post treatment scrotal and oral Behcet’s’s lesions for clinicians to memorize. We also discussed international criteria to diagnose Behcet’s disease (ICBD) in concurrence with our case. In this presentation, we briefly described the involvement of other systems and their treatment. This article also elaborated on the latest developments in the treatment of Behcet’s disease.

Diferencias en la conclusión final de la búsqueda de anticoagulante lúpico en pacientes anticoagulados con antagonistas de la vitamina K / Differences in the final conclusion of the search for lupus anticoagulant in patients anticoagulated with vitamin K antagonists

Resumen Introducción. La detección de anticoagulante lúpico (AL) en pacientes que reciben el tratamiento con antagonistas de la vitamina K (AVK) es todavía una asignatura pendiente. Algunas guías recomiendan realizar todas las pruebas en la mezcla equimolar del plasma del paciente y el pool de plasmas normales (PN+PP), en aquellos pacientes con RIN<3. Sin embargo, la última guía de la ISTH sugiere no determinar AL en pacientes con AVK. Objetivo. Comparar la conclusión final de los estudios de AL, realizando las pruebas de tamizaje y confirmatorias en el plasma puro (PP) y en la mezcla (PP+PN), en pacientes en tratamiento con AVK. Población. 90 pacientes con diagnóstico previo de AL persistente, que al momento de su inclusión estaban en tratamiento con AVK con RIN < 3. Todos habían sido estudiados por segunda vez para confirmar el diagnóstico de AL persistente, a los tres meses, bajo tratamiento anticoagulante con heparina de bajo peso molecular y luego continuaron con el tratamiento con AVK. Materiales y métodos. Se realizaron los ensayos de tamizaje y confirmatorio del tiempo de veneno de víbora de Russell (dRVVT y cRVVT) y del tiempo de coagulación de sílice (sSCT y cSCT). Se preparó el pool de plasmas normales con 40 donantes de sangre, que fueron negativos para la evaluación de AL. Los puntos de corte fueron establecidos localmente de acuerdo a la guía ISTH. Resultados. 33/90 pacientes fueron AL positivo tanto en PP como en PP+PN, 27 negativos y 30 discordantes. 46 de las 90 muestras fueron positivas por dRVVT en PP, pero sólo 18/90 fueron positivas por ensayo de dRVVT en PP+PN. El valor de kappa para la medida de la concordancia entre el ensayo dRVVT en ambas situaciones fue de 0,21 (IC del 95 % = 0,047-0,374). 52/90 fueron negativos por ensayo SCT en PP y 50/90 fueron negativos en PP+PN. 31/90 fueron positivos en ambos casos. Sólo 9/90 fueron positivos por SCT en PP+PN y negativos en PP. El índice kappa para el SCT fue 0,64 (0,431-0,844). Discusión. Aunque realizar las pruebas de AL en PP+PN en pacientes anticoagulados con AVK es una práctica habitual, de acuerdo con estos resultados no es una buena opción, porque podría dar un diagnóstico falsamente negativo o positivo, dependiendo del ensayo. La discrepancia entre usar o no la mezcla es mayor en el ensayo de Drvvt.

Abstract Introduction. The detection of lupus anticoagulant (LA) in patients who are on vitamin K antagonist (VKA) treatment is still an unresolved issue. Some guidelines recommend performing all tests on the equimolar mixture of the patient's plasma plus normal plasma pool (PN+PP) in those patients with INR<3. However, the latest ISTH guideline suggests not determining LA in patients with VKA. AIM. To compare the final conclusion of LA studies, performing screening and confirmatory tests in pure plasma (PP) and in the mixture (PP+PN), in patients receiving VKA treatment. Population. 90 patients with a previous diagnosis of persistent AL, who at the time of inclusion were in treatment with VKA with INR < 3. All had been studied for a second time to confirm the diagnosis of persistent LA, three months later, under anticoagulant treatment with low molecular weight heparin and then continued treatment with VKA. Materials and methods. Screening and confirmatory tests of Russell's viper venom time (dRVVT and cRVVT) and silica coagulation time (sSCT and cSCT) were performed. The normal plasma pool was prepared with 40 blood donors, who were negative for the AL evaluation. The cut-off points were established locally according to the ISTH guideline. Results. 33/90 patients were LA positive considering PP and PP+PN, 27 were negative and 30 discordant. 46 of the 90 samples were positive by dRVVT in PP but only 18/90 were positive by dRVVT assay in PP+PN. The kappa value for the measure of agreement between the dRVVT test in both situations was 0.21 (95% CI = 0.047-0.374). 52/90 were negative by SCT assay in PP and 50/90 were positive in PP+PN. Only 9/90 were positive by SCT in PP+PN and negative in PP. The kappa index for the SCT was 0.638 (0.431-0.844). Discussion. Although performing LA tests on the PP+PN mixture in anticoagulated patients with VKA is a common practice, according to these results, it is not a good option because they could give a false negative or positive diagnosis, depending on the assay. The discrepancy between using or not using the mixture is greater in dRVVT´s assay.

Research progress on P2X7 receptor in cancer pain / 基础医学与临床

The activation of the P2X7 receptor as an ATP-gated ion channel,triggers the release of pro-inflammato-ry cytokines in tumor carring individuals and stimulate excitation of injury-causing neurons,thereby exacerbating the transmission of pain.In preclinical cancer pain models,it has the potential to serve as a new therapeutic target for cancer pain management.

Expression of N-methyl-D-aspartic acid receptor and endoplasmic reticulum stress related pathway proteins in brain tissue of fluorosis rats / 中国组织工程研究

BACKGROUND:Previous studies have shown that N-methyl-D-aspartic acid receptor(NMDA)receptors are associated with fluorine,but the role in fluoride-induced endoplasmic reticulum stress remains unclear. OBJECTIVE:To observe the changes of excitatory neurotransmitter NMDA receptor and endoplasmic reticulum stress IRE1α-ASK1-JNK pathway protein expression in brain tissue of rats with experimental fluorosis,and to investigate the pathogenesis of neurological injury in fluorosis by giving NMDA receptor inhibitor to SH-SY5Y cells. METHODS:(1)Animal model:18 1-month-old SD rats were randomly divided into control group(drinking water fluoride content<0.5 mg/L),low fluoride group(drinking water fluoride content 10.0 mg/L)and high fluoride group(drinking water fluoride content 100.0 mg/L),with 6 rats in each group,half of each sex.After 6 months of fluoride intake,the rats were observed for the occurrence of dental fluorosis,and the 24-hour urinary fluoride content was measured.After anesthesia and euthanasia,the brain tissue of rats was taken to observe the pathological changes.Western blot assay was used to detect NMDA receptors and IRE1α,ASK1 and JNK protein expression in the brain tissue.(2)Cell model:SH-SY5Y cells were cultured in vitro and treated with sodium fluoride at final concentrations of 0.3 mmol/L and 3 mmol/L.The fluoride-stained cells were interfered with 10 μmol/L NMDA receptor antagonists Ifenprodil and MK-801 to observe the relevant protein changes. RESULTS AND CONCLUSION:(1)The incidence of dental fluorosis and urinary fluoride level in rats in the high fluoride group were significantly higher than that in the control and low fluoride groups(P<0.05).(2)Compared with the control group,the cytoplasm of neuronal cells in the CA3 area of the hippocampus in the low fluoride group was slightly more basophilic,while the neuronal cells in the CA3 area of the high fluoride group were disorganized,with increased basophilicity and some of the nuclei solidified.(3)In rat brain tissue,the expressions of NR2A in the high fluoride group and NR2B in the low fluoride group were significantly higher compared with the control group(P<0.05),and NR2B,IRE1,ASK1,and p-JNK protein expression levels were increased in the high fluoride group compared with the control and low fluoride groups(P<0.05).(4)In SH-SY5Y cells,NR1,NR2A and NR2B protein expressions were significantly increased in the high fluoride group compared to the control group(P<0.05).The protein levels of NR1 and NR2A were significantly reduced in the high fluorine + Ifenprodil group and high fluorine + MK-801 group compared with the high fluorine group(P<0.05).NR2B protein expression was significantly lower in the high fluorine + Ifenprodil group than that in the high fluorine group(P<0.05).(5)In SH-SY5Y cells,IRE1,ASK1,and p-JNK protein expression was significantly higher in the high fluoride group compared with the control group(P<0.05),while ASK1 and p-JNK protein expressions were significantly decreased in the high fluorine + Ifenprodil group and high fluorine + MK-801 group compared with the high fluorine group(P<0.05).IRE1 protein level was significantly lower in the high fluorine + Ifenprodil group than that in the high fluorine group(P<0.05).(6)It is concluded that excessive fluorine intake activates NMDA receptors in the central nervous system,causing increased expression of endoplasmic reticulum stress IRE1α,ASK1,and p-JNK proteins,and the use of NMDA receptor inhibitors has a mitigating effect on endoplasmic reticulum stress caused by fluorosis.

The effects of attenuated Salmonella carrying IL-2/NK4 double gene on immune function in mice / 中国生物制品学杂志

@#Objective To study the effects of attenuated Salmonella(Ty21a-pIRES-IL-2-NK4,TPIN)carrying interleukin-2(IL-2)/4-kringle antagonist of hepatocyte growth factor(NK4)double gene on humoral and cellular immune function.Methods Eighteen BALB/c mice,half male and half female,were randomly divided into control group(1. 5 mL 10%NaHCO3 by gastric tube feeding),Ty21a group(0. 1 mL Ty21a by gastric tube feeding)and TPIN group(0. 1 mL TPIN by gastric tube feeding),with 6 mice in each group. The immunization was boosted twice 7 d after the initial immunization. At 21d after administration,the blood samples were collected from eyeballs and the serum was separated,which was detected for the serum IgG antibody level by ELISA. The thymus and spleen of mice were isolated aseptically,and the spleen cells were stimulated by Ty21a and TPIN respectively in vitro. After 72 h,the proliferation ability of spleen cells was measured by CCK-8 assay,and the expression level of cytokines in spleen cells was detected by ELISA. The spleen and thymus were weighed,the spleen and thymus indexes were analyzed,and HE staining was performed.Results Compared with the control group and Ty21a group,the serum IgG level(F = 111. 74,P < 0. 01)and the contents of IFNγ,IL-4 and IL-10 in spleen cell supernatant(F = 38. 21,11. 37 and 26. 92,respectively,each P < 0. 05)increased significantly,as well as the spleen and thymus indexes(F = 10. 419 and 5. 859,respectively,each P < 0. 05)showed significant increase. In mice of Ty21a and TPIN group,the thymus cortex widened,lymphocytes increased,and there was mild inflammatory reaction;the white pulp and lymphocytes in spleen increased with neutrophil infiltration.Conclusion TPIN has a good immune protective effect,and can significantly stimulate the body to produce humoral immunity and cellular immunity,which may have a good therapeutic effect on tumors.

Construction,expression,purification and quality identification of kanamycin resistant strain of recombinant human interleukin-1 receptor antagonist / 中国生物制品学杂志

@#Objective To construct a recombinant human interleukin-1 receptor antagonist(rhIL-1Ra)strain of kanamycin resistance,express,purify and identify rhIL-1Ra protein in order to reduce the risks of β-lactam antibiotics.Methods The ampicillin-resistant rhIL-1Ra(A-rhIL-1Ra)plasmid and PET-28a plasmid were used as templates to prepare the linearized vector and kanamycin gene fragment by PCR.The kanamycin resistant rhIL-1Ra plasmid(K-rhIL-1Ra)was constructed by homologous recombination,which was transformed into E.coli BL21(DE3)to construct the recombinant engineered bacteria after correct sequencing.The engineered bacteria were induced by IPTG and then purified by CM Bestarose Fast Flow and DEAE Bestarose Fast Flow column chromatography.The purified products were collected,and then detected for the purity by 15% SDS-PAGE,size-exclusion high-performance liquid chromatography(SEC-HPLC),and reversed-phase high-performance liquid chromatography(RP-HPLC),determined for the relative molecular mass by tandem mass spectrometry,identified for the specificity by Western blot,measured for the biological activity by reporter gene assay,and compared for the related impurities by liquid chromatography-mass spectrometry(LC-MS)analysis.Results Colony PCR and sequencing results showed that K-rhIL-1Ra plasmid was constructed correctly.The expressed K-rhIL-1Ra protein had a relative molecular mass of about 17 000,mainly existing in soluble form,and the expression amount accounted for more than 30% of the total bacterial proteins.The purity of K-rhIL-1Ra protein purified by two steps was 97% and 99%,the monomer content was 99.33%and 100%,and the chromatographic purity was 91.86% and 96.96%,respectively.The mass spectral molecular mass was consistent with that of the standard(A-rhIL-1Ra protein),and the protein reacted specifically relative with mouse antihuman IL-1Ra monoclonal antibody.The biological activity of the purified K-rhIL-1Ra protein was 1.29 × 105U/mg,and the chemical modification types of related proteins were the same as those of the standard(A-rhIL-1Ra protein).Conclusion The K-rhIL-1Ra strain was successfully constructed,and the expressed and purified protein was in line with the characteristics and quality standards of rhIL-1Ra,which lays a foundation for the study of rhIL-1Ra strain change and comparability

Network meta-analysis of triple therapy for the prevention and treatment of acute nausea and vomiting caused by emetogenic chemotherapy drugs with moderate and high risk / 中国药房

OBJECTIVE To evaluate the efficacy of the triple therapy of 5-HT3 receptor antagonists， neurokinin-1 receptor antagonists and dexamethasone （referred to as “triple therapy”） in the prevention and treatment of acute nausea and vomiting caused by moderately and highly emetogenic chemotherapy drugs. METHODS Retrieved from PubMed， Embase， the Cochrane Library， CNKI and Wanfang data， randomized controlled trials （RCTs） about triple therapy or 5-HT3 receptor antagonist combined with dexamethasone （referred to as “dual therapy”） were collected during the inception to May 2023. After literature screening， data extraction and literature evaluation， network meta-analysis was performed by using Stata 16.0 software. RESULTS A total of 59 RCTs were included， involving 23 418 patients and 15 interventions. Results of network meta-analysis showed that fosaprepitant + palonosetron + dexamethasone （FPD） was most effective in terms of acute nausea and vomiting control rate， followed by fosaprepitant + granisetron + dexamethasone （FGD） and aprepitant + ramosetron + dexamethasone （AMD）. In terms of acute nausea control rate， FPD was the most effective， followed by aprepitant + palonosetron + dexamethasone （APD） and FGD. In terms of acute vomiting control rate， FPD was the most effective， followed by FGD and APD. CONCLUSIONS Fosaprepitant + palonosetron + dexamethasone is better than other triple therapy or dual therapy in preventing acute nausea and vomiting caused by moderately and highly emetogenic chemotherapy drugs.

Navafenterol, a new drug for the treatment of chronic obstructive airway disease / 中国临床药理学与治疗学

Navafenterol is a new compound with both muscarinic receptor antagonist and β2 receptor agonist effects in a single molecule, who is being developed for the treatment of chronic obstructive airway disease such as chronic obstructive pulmonary disease and asthma. These pilot clinical studies found that it can significantly improve lung function and symptoms, and is safe and well tolerated. Common treatment emergent adverse events include headache, nasopharyngitis, and dizziness. It may become a next-generation bronchodilator for chronic obstructive airway disease. This review introduced the prospective of Navafenterol.

Development and verification of a detection method for activity of neutralizing antibody in ELISA antibody positive serum of rats immunized with recombinant human interleukin-1 receptor antagonist / 中国生物制品学杂志

@#Objective To develop and verify a method for detecting the activity of neutralizing antibodies in ELISA antibody positive serum of rats immunized with recombinant human interleukin-1 receptor antagonist(rhIL-1Ra). Methods The SD rats were subcutaneously immunized with 3,20 and 100 mg/kg rhIL-1Ra injection respectively,10 rats in each group,half male and half female,twice a day at an interval of at least 4 h between each dose for 13 consecutive weeks. The blood samples were collected from the jugular vein of rats during the administration period and the recovery period. The serum samples were isolated and detected for the antibody titers by ELISA,and the samples positive for rhIL-1Ra antibody were purified by Protein A chromatographic column. Based on,D10G4·1 cells biological activity assay,a method for the detection of neutralizing antibody activity was developed and verified for the specificity,sensitivity and precision. The neutralizing antibody activity of rhIL-1Ra antibody positive serum determined by ELISA was detected by using the developed method.Results With the increase of doses,the serum antibody titers of rats in various dose groups gradually increased,and there were still antibodies in the recovery period,and the titer was still high. Rabbit anti-rhIL-1Ra monoclonal antibody showed obvious neutralizing effect on rIL-1Ra,while rabbit anti-rIFN-2b monoclonal antibody had no dose-effect relationship with rIL-1Ra. The sensitivity of the method was 171. 93 μg/mL;The CVs of precision verification were not more than 20%. The positive antibody sera detected by ELISA all had neutralizing effect on rhIL-1Ra injection,which was consistent with the results detected by ELISA. Conclusion The method developed in this study has good specificity and high sensitivity in the detection of serum neutralizing antibody activity in rats immunized with rhIL-1Ra,which can be used to detect the serum neutralizing antibody activity of animals with rhIL-1Ra repeated administration.

Effects of the 5-HT1A receptor antagonist on synaptic plasticity in sevoflurane-induced cognitive dysfunction in aged rats and its mechanism / 中国医科大学学报

Objective To investigate the effect of the 5-HT1A receptor antagonist on synaptic plasticity in flurane-induced cognitive dys-function in aged rats.Methods Thirty 18-month-old Sprague-Dawley rats were randomly divided into control,model,and drug groups.The model group inhaled a 50%oxygen gas mixture(2 L/min)and 2%sevoflurane and were then treated with 5μL 0.9%NaCl;the drug group inhaled a 50%oxygen mixture(2 L/min)and 2%sevoflurane for 4 h and then the 5-HT1A receptor antagonist(3μg)was injected into the left ventricles of the rats;and the control group inhaled a 50%oxygen mixture(2 L/min)for 4 h.The water maze method was used to assess the learning memory of the rats and histopathological changes in the rat hippocampus were examined by HE staining.Nissl and Golgi staining were used to identify any changes to the neurons and synapses in hippocampal tissue.The MeCP2,p250GAP,PSD-95,GAP-43,and Syn expression levels were determined by immunofluorescence assay and the PKA,CREB1,and BDNFmRNA levels were determined using real-time PCR.Western blotting was performed to determine the PKA,CREB1,p-CREB1,and BDNF expression levels.Results The water maze data showed that the escape latency was significantly prolonged in the model group compared to the control group and,after treatment with the 5-HT1A receptor antagonist,the escape latency significantly decreased in the drug group compared to that of the model group(P<0.05).Moreover,the number of platform crossings was significantly lower in the model group than in the control group,but the number of platform crossings in the drug group was significantly higher than that in the model group(P<0.05).Compared to the control group,the hippocampal neurons in the model group had irregular morphology,loosely arranged and enlarged sur-rounding tissue gaps,deeply stained nuclei,a reduced number of Nissl bodies in the neurons,and a significantly reduced dendritic spine density and number of branches.After treatment with the 5-HT1A receptor antagonist,the hippocampal neurons in the drug group had a regular morphology,relatively complete structure,uniform arrangement,increased numbers of Nissl bodies in the neurons,and a signifi-cantly increased dendritic spine density and number of dendritic branches.Compared to the control group,MeCP2,PSD-95,GAP-43,Syn,PKA,CREB1,p-CREB1,and BDNF expression levels significantly decreased and p250GAP expression significantly increased in the rat brain tissue from the model group(P<0.05),but the PKA,CREB1,and BDNF mRNA levels significantly decreased(P<0.05).Furthermore,compared to the model group,the MeCP2,PSD-95,GAP-43,Syn,PKA,CREB1,p-CREB1,and BDNF expres-sion levels significantly increased along with the PKA,CREB1,and BDNF mRNA levels(P<0.05)in the drug group.However,the p250GAP protein expression level significantly decreased(P<0.05).Conclusion The 5-HT1A receptor antagonist improves learning memory in rats with sevoflurane-induced cognitive dysfunction.Specifically,it enhances PSD-95,GAP-43,and Syn expression levels,pro-motes synaptic remodeling,and protects rat hippocampal neuronal cells by activating the CREB/BDNF pathway.

Role of cetrorelix in the prevention and treatment of ovarian hyperstimulation syndrome: a prospective case control study

Background: Ovarian hyperstimulation syndrome (OHSS) has intrigued clinicians for many years because of its devastating consequences. As an iatrogenic condition resulting from elective ovarian stimulation in the quest for pregnancy, the need to completely prevent the syndrome is evident. Gonadotropin releasing hormone (GnRH) antagonist Cetrorelix has found to be effective in treatment of OHSS and some studies have found it to be helpful in prevention of this condition. Hence, we designed a hospital-based study to investigate the effect of Cetrorelix in preventing and treating OHSS in in-vitro fertilization � embryo transfer (IVF朎T) patients at risk of OHSS undergoing long and short protocol.Methods: The study includes total 102 patients undergoing controlled ovarian stimulation COS for IVF/ICSI. All cases were stimulated using long and short protocol. Depending on whether a GnRH antagonist was given after ovum pick-up (OPU) the patients were divided in two groups: Cetrorelix (antagonist) group (n=51) and control group (n=51). The study group was treated with Cetrorelix 0.25 mg for 5 days commencing on the day of ovum pick up.Results: Incidence of mild OHSS was significantly higher (p=0.01) whereas moderate to severe OHSS was significantly lower in the antagonist group (p<0.05). None of the patients had critical OHSS.Conclusions: GnRH antagonist Cetrorelix administration in early luteal phase in patients undergoing long or short protocol is effective in prevention and treatment of OHSS.

In vivo Bio-efficacy of Fungicides and Antagonists for the Management of Target Leaf Spot of Soybean [Corynespora cassiicola (Berk. and Curt.) Wei]

Foliar diseases cause major qualitative and quantitative yield loss in soybean, among which target leaf spot of soybean caused by Corynespora cassiicola is one of the constraints. Hence, management of this disease is much needed effort. Thus the present investigation was carried out for management of the disease under field condition using fungicides and bioagents that were effective in inhibiting the pathogen under in vitro studies. Among the different treatments evaluated, seed treatment with (pyraclostrobin 5% + thiophanate methyl 45%) @ 2 ml/kg seed followed by spray with (tebuconazole 50% + trifloxystrobin 25%) @ 0.05% at 55 and 75 days after sowing (DAS) recorded the least disease severity of 2.23 percent with higher seed yield (17.20 q/ha) and test weight (17.41 g) as compared to untreated check which recorded disease severity of 27.50 percent. Apart from the target disease, other diseases like rust, anthracnose and Alternaria leaf spot were also take care in the same treatment. Use of fungicides for the management of disease in the absence of resistant genotypes is an old practice and it is one of the best options when there is outbreak.

Characterization of Native Fluorescent Pseudomonads against Sclerotinia Blight of Brinjal (Solanum melongena L.)

Brinjal (Solanum melongena L.) is one of the most common and known rich source of vitamin B1 (Thiamin), dietary fibre, manganese, niacin (vitamin B3), copper, vitamin B6 (pyridoxine), folate (vitamin B9), potassium, Vitamin K. Brinjal cultivation is affected by several pests and diseases. Sclerotinia blight is one of the most destructive diseases of brinjal caused by Sclerotinia sclerotiorum (Lib) de Bary. Under the present investigation two isolates of Fluorescent Pseudomonads (FLPs) viz., FLP-Brinjal 2020-1 and FLP-Brinjal 2020-2, were evaluated against Sclerotinia sclerotiorum (SCL)under in vivo and in vitro conditions using dual culture, inverted plate assay. FLP-Brinjal 2020-2 gave maximum inhibition over the control followed by FLP-Brinjal 2020-1 against the pathogen in in vitro condition. Experiments conducted in pluck trays indicated that FLP-Brinjal 2020-2 was superior with least sclerotinia blight incidence (20.53%).The identity and diversity among the FLP isolates were examined by sequence analysis of 16s rRNA gene. The gene was amplified by PCR using primers pair, 27 F/1492 R. Amplified DNA products were sequenced and analysed by BLAST (BLASTn) programme at NCBI database for species identification. Among the 10 FLPs isolates assessed 9 were found to have maximum similarity with Pseudomonas aeruginosa. FLP 2020-2 and FLP 2020-1 were found to be Pseudomonas fluorescence which is in confirmation with the morphological observations. Significant diversity among the isolates was observed when dendrogram of the sequence was plotted using CLUSTAL W.

Clínicas de ketamina: usos actuales según la evidencia / Ketamine clinics: current uses based on evidence

Resumen: La ketamina es un medicamento conocido por sus bondades como inductor anestésico y para disminuir la posibilidad de complicaciones, por ejemplo, exacerbación del dolor neuropático e hiperalgesia asociada a opioides. En esta revisión nos enfocaremos en otras indicaciones en las que también ha demostrado ser útil y que, bajo observación e instrucción adecuadas en una infraestructura diseñada para ello (clínicas de ketamina), mejora la calidad en el comportamiento y disminuye el estrés, ansiedad y dolor. Entre las indicaciones para su uso se encuentran los trastornos depresivos, el trastorno de ansiedad, el trastorno obsesivo compulsivo y los relacionados con traumas emocionales; el trastorno bipolar, anormalidades en conducta e ingesta alimentaria, al igual que los trastornos adictivos.

Abstract: Ketamine is a drug known for its benefits as an anesthetic inducer and to reduce the possibility of complications such as exacerbation of neuropathic pain and hyperalgesia associated with opioids. In this review we will focus on other indications in which it has also proven to be useful and that, under adequate observation and instruction in an infrastructure designed for it (ketamine clinics), improves the quality of behavior and decreases stress, anxiety and pain. Among the indications for its use are depressive disorders, anxiety disorder, obsessive-compulsive disorder and those related to emotional trauma; bipolar disorder, abnormalities in behavior and eating intake as well as addictive disorders.

A bullous variant of central serous chorioretinopathy treated with oral spironolactone / Uma variante bolhosa da coriorretinopatia serosa central tratada com espironolactona oral

ABSTRACT We report the case of a 39-year-old male patient who presented with visual loss in the right eye for 6 weeks. The best-corrected visual acuity was counting fingers in the right eye and 20/30 in the left eye. The fundus examination demonstrated a right retinal detachment inferiorly extending to the fovea and a left macular serous detachment. After multimodal imaging study, the patient was diagnosed as having a bullous variant of central serous chorioretinopathy and treated with oral spironolactone associated with adjuvant laser photocoagulation. The retinal changes resolved after 6 months. The final visual acuity was 20/20 in both eyes.

RESUMO Relatamos o caso de um homem de 39 anos apresentando perda visual no olho direito há seis semanas. A melhor acuidade visual corrigida foi conta-dedos no olho direito e 20/30 no esquerdo. A fundoscopia demonstrou descolamento de retina direito inferiormente com extensão à fóvea e descolamento macular seroso à esquerda. Após estudos de imagem multimodal, o paciente foi diagnosticado com uma variante bolhosa de coriorretinopatia serosa central e tratado com espironolactona oral associada à fotocoagulação a laser adjuvante. As alterações retinianas resolveram após seis meses. A acuidade visual final foi 20/20 em ambos os olhos.

Addition of gonadotropin releasing hormone antagonist for women undergoing intrauterine insemination: a randomized controlled trial

Background: Intrauterine insemination (IUI) is a widely acceptable fertility treatment modality. GnRH antagonists have been proven effective in restricting the LH surge. The aim of the study was to assess whether the addition of gonadotropin releasing hormone antagonist (Cetrorelix) would improve clinical pregnancy rate in women undergoing IUI. Methods: This prospective randomized controlled trial was conducted at a Sudha fertility center where 730 women with primary or secondary infertility were subjected to controlled ovarian stimulation with tablet letrozole 5mg once daily for 5 days and then human menopausal gonadotrophins 75 IU/150 IU administered intramuscularly for both the groups and for study group alone Cetrorelix (0.25 mg/day, started when the leading follicle was ?16 mm; GnRH antagonist) was given additionally. A double insemination was performed at 36 hours and 60 hours after hCG was given (5,000 IU, intramuscularly) in both groups. Chi-square and independent t test was done.Results: Baseline characteristics in both the groups were almost equal without any statistically significant difference. Significant difference (p=0.017) was found on calculating with statistics among both groups on analyzing LH on hCG day. Clinical pregnancy rates (29.3%) were higher among the study group compared with the control group (21.7%).Conclusions: From the present study results it shows that addition of GnRH antagonists to controlled ovarian stimulation IUI significantly decreases the incidence of premature luteinization and increases the clinical pregnancy rates and live birth rate.

The effect of early radiofrequency turbinate reduction, intranasal steroid, and antihistamine H-1 on persistent allergic rhinitis: a randomized clinical trial

Abstract Objective: We aimed to evaluate the effect of radiofrequency turbinate reduction as an initial treatment on clinical improvement, inflammatory mediators, and remodeling process. Methods: Between July 2018- February 2020, 32 patients with moderate-severe persistent AR were randomly divided into 2 groups. Intervention group received radiofrequency turbinate reduction followed by intranasal steroid and Antihistamine H-1 (AH-1), control group received intranasal steroid and AH-1. Both groups were evaluated for clinical improvement (using visual analogue scale based on total nasal symptoms score, peak nasal inspiratory flow, and turbinate size using imageJ) after 4 and 8 weeks of treatment. Inflammatory mediators (ELISA from nasal secretions was performed to measure ECP, IL-5, and HSP-70) and remodeling markers (nasal biopsy followed by immunohistochemistry examination was performed to evaluate MMP-9, TIMP-1, and PAI-1) were evaluated in week 4. Results: Three patients dropped out of the study, resulting in 16 patients in intervention group and 13 patients in control group. At week 4, clinical response improved significantly in the intervention group compared to control group (Chi-Square test, p<0.05). Compared to control, intervention group experienced a reduction of IL-5 and no significant change in ECP level (Mann Whitney test, p>0.05). Reduction in the ratio of MMP-9/TIMP-1 were significantly higher in intervention group (unpaired t-test, p< 0,05). Meanwhile, increase in HSP-70 in the intervention group was slightly lower than in control group, but the difference with control group was not significant (Mann Whitney test, p>0.05). Conclusion: Early radiofrequency turbinate reduction followed by pharmacotherapy given to persistent moderate-severe AR patients give more improvement only in early clinical symptoms and reduce MMP-9/TIMP-1 ratio, thus it might be suggested as one of the adjuvant therapies for the management of moderate-severe persistent AR. However, further investigation with a larger sample size and longer follow-up period is needed. Level of evidence: 1B.

Comparative evaluation of metformin & sitaformin in classic PCOS patients undergoing intracytoplasmic sperm injection: A randomized controlled pilot study

Background & objectives: Studies have shown that insulin resistance and hyperinsulinaemia play a major role in the pathogenesis of polycystic ovary syndrome (PCOS). Therefore, the use of insulin sensitizing drugs in the treatment of PCOS has attracted the attention of medicine and researchers. The aim of this study was to investigate the effects of sitaformin (sitagliptin/metformin) and metformin on the quality of oocyte and embryo in classic PCOS patients undergoing intracytoplasmic sperm injection (ICSI). Methods: Sixty patients of PCOS (25-35 yr) were randomly allocated into three groups (n=20, each group): a metformin-treated group (administered metformin 500 mg twice daily), a sitaformin-treated group (administered sitaformin 50/500 mg twice daily) and a placebo group. Participants in all the groups received the drug two months prior to the start of the ovulation cycle and treatment continued until the day of the oocyte aspiration. Results: Serum insulin and total testosterone levels decreaseed significantly after treatment in both the treatment groups as compared to the placebo (P<0.05). A significant decrease in the number of immature oocytes [MI + germinal vesicle (GV) stage] was observed in metformin and sitaformin groups as compared to the placebo. In addition, sitaformin group when compared to the metformin group showed a significant decrease in the number of immature oocytes (P<0.05). The number of mature and normal MII oocytes increased significantly in both the treatment groups compared to the placebo group (P<0.05). The number of mature and normal oocytes increased in sitaformin group in comparison to the metformin group, but the difference was not significant. There was a significant increase in the number of grade I embryos, fertilization and cleavage rates in the sitaformin group compared to the other groups (P<0.05). Interpretation & conclusions: This is the first study to compare the impact of sitaformin with metformin on oocyte and embryo quality in women with PCOS undergoing a gonadotropin-releasing hormone (GnRH) antagonist cycle. In conclusion, sitaformin can be more effective in decreasing immature oocytes and increasing the quality of embryos than the use of metformin.

Changes of RAGE/p38MAPK/NF-κB signaling pathway in brain tissue of subchronic fluorosis rats and protective effects of Ginkgo biloba extract and RAGE antagonist / 环境与职业医学

Background Fluorine accumulates in the brain tissue after long-term excessive intake and subsequently cause nerve damage and decline of learning and memory ability. Receptor of advanced glycation end-products (RAGE)/p38 mitogen-activated protein kinase (p38MAPK)/nuclear factor kappa-B (NF-κB) signaling pathway is considered to be involved in the associated mechanism. Objective To study the changes of RAGE/ p38MAPK/ NF-κB signaling pathway in rats with subchronic fluorosis, and to explore the protective effects of extract of Ginkgo biloba 761 (EGb761) and RAGE antagonist (FPS-ZM1) on neuromemory ability. Methods Ninety male clean SD rats were divided into 9 groups with 10 rats in each group. The modeling period was 6 months. Control group (C group): free drinking tap water (fluoride content <0.5 mg·L−1), low- and high-dose fluoride groups (LF group, HF group): free drinking tap water with 10 or 50 mg·L−1 fluoride; intervention group of Ginkgo biloba extract (CE, LFE, and HFE groups): on the basis of the C group, LF group, and HF group, 100 mg·kg−1·d−1 EGb761 was given daily via intragastric administration; FPS-ZM1 intervention groups (CF, LFF, and HFF groups): 7 d before the end of modeling, 1 mg·kg−1·d−1 FPS-ZM1 was injected intraperitoneally daily on the basis of the C group, LF group, and HF group. The contents of fluoride in brain and blood of each group were detected. The learning and memory ability was tested by water maze experiment. The histopathologic changes of the hippocampus were detected by Nissl staining. The protein expression levels of RAGE and its ligand high mobility group protein B1 (HMGB1), NF-κB, p38MAPK, phospho-p38MAPK (p-p38MAPK), interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α) in brain tissue were detected by Western blotting. The mRNA expression levels of RAGE, HMGB1, and p38MAPK were detected by quantitative real-time PCR. Results Compared with the C group, the contents of blood fluoride and brain fluoride in the LF and the HF groups were increased (P<0.05). The results of the water maze experiment showed that, compared with the C group, the escape latency time of the LF group and the HF group was longer and the crossing times were reduced; compared with the HF group, the escape latency time of the HFE group and the HFF group was shortened, and the crossing times were increased (P<0.05). The Nissl staining results showed that the number of Nissl body in the HF group decreased compared with the C group; compared with the HF group, the number of Nissl body in the HFE group and the HFF group increased. The Western blotting results showed that compared with the relative protein expression levels of RAGE, HMGB1, NF-κB, p38MAPK, p-p38MAPK, IL-6, and TNF-α in the C group , the levels of above indicators in the HF group and the levels of RAGE, HMGB1, NF-κB, p-p38MAPK, and IL-6 in the LF group were up-regulated (P<0.05); compared with the HF group, the levels of above indicators in the HFE group and the HFF group were all down-regulated (P<0.05); compared with the relative protein expression levels of RAGE and HMGB1 in the LF group, the levels in the LFE group and the LFF group were all down-regulated (P<0.05). The quantitative real-time PCR results showed that compared with the C group, the mRNA expression levels of RAGE and HMGB1 in the LF group and the HF group were up-regulated; compared with the LF group, the mRNA expression levels of RAGE in the LFE group and the LFF group were down-regulated ; compared with the HF group, the mRNA expression levels of RAGE and HMGB1 in the HFE group and the HFF group were down-regulated (P<0.05). Conclusion The central nervous system injury caused by subchronic fluorosis may be related to the activation of RAGE/p38-MAPK/NF-κB signaling pathway, which can impair the learning and memory ability of rats, while EGb761 and FPS-ZM1 may have certain protective effects on the nerve injury.

Effect of Elevated Basal LH on IVF-ET Outcomes in Patients with Polycystic Ovary Syndrome / 中山大学学报(医学科学版)

ObjectiveTo compare the outcomes in controlled ovarian stimulation （COH） and fresh embryo transfer between women with and those without a high basal luteinizing hormone （bLH） level in polycystic ovary syndrome （PCOS）. MethodsThe clinical data of PCOS patients at the Reproductive Medicine Center of the Sixth Hospital of Sun Yat-sen University from January 2015 to December 2021 were retrospectively analyzed. They were divided into the high group （LH≥10 U/L） and normal group （LH<10 U/L） according to the bLH levels. The results of COH and pregnancy outcomes after fresh transfer were compared， including gonadotropin （Gn） initiation dose， Gn duration， total Gn dose， number of oocytes obtained， two pronuclei （2PN） rate， available embryos rate， high-quality embryos rate， blastocyst formation rate， human chorionic gonadotrophin （HCG） positive rate， clinical pregnancy rate （CPR）， spontaneous abortion rate （SAR）， ongoing pregnancy rate （OPR） and live birth rate （LBR）. The differences in hormonal trends during COH were also analyzed. ResultsThere were no statistically significant differences in age， body mass index， anti-Mullerian hormone， and type of infertility between the two groups. Compared with the normal group， the Gn initiation dose and Gn duration were not statistically significant （P>0.05）， while the total Gn dose was significantly lower （P<0.001） in the high group. The number of oocytes retrieved， 2PN rate， available embryos rate， high-quality embryos rate， and blastocyst formation rate were comparable between the two groups （all P>0.05）. After fresh embryo transfer， they had similar pregnancy outcomes in the HCG positive rate， CPR， SAR， OPR and LBR （all P > 0.05）. ConclusionsIn patients with PCOS， high bLH levels do not affect COH or pregnancy outcomes in fresh transfer cycles. Further studies are needed to determine whether LH levels need to be lowered prior to COH and whether frozen-all strategy is required in patients with elevated bLH levels.