Determinación del pH salival después de la aplicación de aceite ozonizado / Determination of salivary pH after application of ozonated oil

La saliva, compuesta principalmente por 99% de agua y 1% de moléculas orgánicas e inorgánicas, mantiene un rango de pH de 6.0 a 7.5, pero puede verse alterada por ciertos factores. En este estudio se determinó la variación del pH salival, luego de la aplicación tópica manual en mucosa masticatoria y órganos dentarios con aceite de girasol ozonizado de 300 mEq/kgO2, en jóvenes estudiantes de entre 21 a 23 años, como agente de neutralización en los cambios de pH. Se realizó un estudio comparativo longitudinal en 13 sujetos después de su cepillado dental; se tomaron dos muestras en saliva estimulada con el test estandarizado Saliva-Check BUFFER (GC®EUROPE). La medición basal de pH fue 7.66 ± 0.09, cifra por encima del rango normal; después de la aplicación del aceite de girasol ozonizado (O3MX®300IP) el pH fue de 7.27 ± 0.19, estableciéndose una variación de 0.28 ± 0.48, t = 8.04, p < 0.05 (0.000). Este estudio revela una caída significativa en el pH salival después de aplicar aceite de girasol ozonizado, lo que sugiere su potencial como buffer del pH salival. Se necesitan más investigaciones para explorar las implicaciones clínicas para el manejo de la salud oral (AU)

Saliva, primarily composed of 99% water and 1% organic and inorganic molecules, typically maintains a pH range of 6.0 to 7.5 but can be influenced by various factors. This study aimed to assess the variation in salivary pH following manual topical application of 300 mEq/kgO2 ozonated sunflower oil to the masticatory mucosa and dental structures in young individuals aged 21 to 23 years, using it as a pH-neutralizing agent. A longitudinal comparative study was conducted on 13 subjects after dental brushing. Stimulated saliva samples were collected using the standardized Saliva-Check BUFFER Test (GC®EUROPE). An initial baseline pH measurement of 7.66 ± 0.09 was obtained, which was above the normal range. Following the application of ozonated sunflower oil (O3MX®300IP), the pH dropped to 7.27 ± 0.19, indicating a variation of 0.28 ± 0.48 (t = 8.04, p < 0.05 (0.000). In conclusion, this study reveals a significant decrease in salivary pH after applying ozonated sunflower oil, suggesting its potential as a salivary pH buffer. Further research is needed to explore the clinical implications for oral health management.(AU)

Exploring Scientific Connotation of "Fried Charcoal Survivability" of Lonicerae Japonicae Flos Based on Color-composition Correlation / 中国实验方剂学杂志

ObjectiveTo explore the scientific connotation of fried charcoal survivability of Lonicerae Japonicae Flos（LJF） by analyzing the correlation between the color change and the intrinsic components during the processing of LJF Carbonisata（LJFC）， and taking pH， charcoal adsorption and microscopic characteristics as indexes. MethodLJFC samples with different degrees of processing were prepared according to the stir-frying time of 0.0， 1.5， 3.0， 4.5， 6.0， 7.5， 9.0， 10.5 min（numbered S1-S8）， and the contents of gallic acid， chlorogenic acid， cryptochlorogenic acid， rutin， luteoloside， isochlorogenic acid A and isochlorogenic acid C were determined by high performance liquid chromatography（HPLC）， and the L*（brightness）， a*（red-greenness） and b*（yellow-blueness） of LJFC samples with different degrees of processing were determined by spectrophotometer， and the correlation analysis and principal component analysis（PCA） between the contents of seven representative components and the color of the samples were carried out by SPSS 26. 0 and SIMCA-P 14.1. Then pH， adsorption force and characteristic structure of different samples of LJFC were detected and the processing pattern of LJFC was analyzed. ResultThe results of quantitative analysis revealed that the contents of luteoloside， rutin， chlorogenic acid and isochlorogenic acid A gradually decreased， and the contents of cryptochlorogenic acid， isochlorogenic acid C and gallic acid firstly increased and then decreased. The L* and b* of the sample powders decreased， and a* showed a trend of increasing and then decreasing. The L* and b* were positively correlated with the contents of chlorogenic acid， rutin， luteoloside， isochlorogenic acid A， b* was positively correlated with the content of gallic acid， and a* was positively correlated with the contents of cryptochlorogenic acid and isochlorogenic acid C. PCA revealed that samples could be clearly divided into 3 groups， S1-S2 as one group， S3-S5 as one group， and S6-S8 as one group， with S3 having the highest score. The results of regression analysis showed that only isochlorogenic acid C could be used to predict the contents of components by colorimetric values combined with regression equations. Physicochemical analysis showed that pH of LJFC increased with the increase of degree of charcoal stir-frying， while adsorption force showed a tendency of increasing and then decreasing， with the highest adsorption force in the S5 sample， and the non-glandular hairs， calcium oxalate clusters and pollen grains had a varying degree of decreasing with the deepening of processing degree， and the microstructures of S6-S8 samples were obviously charred with pollen grains almost invisible. ConclusionThe changes in chemical composition and color characteristics of LJFC during the processing have certain correlations， combined with the changes in physicochemical properties， S5 sample is found to be the optimal processed products， which can provide a reference for the processing standardization and quality evaluation of LJFC， and enrich the scientific connotation of fried charcoal survivability of LJF.

Lactate and pH values in newborns with a history of acute fetal distress / Valores de lactato y pH en recién nacidos con antecedente de sufrimiento fetal agudo

Abstract Background: Acute fetal distress (AFD) is a condition that requires timely diagnosis because it generates hypoxia, acidosis, and even intrauterine death. This study aimed to determine lactate and pH values in the umbilical cord in full-term newborns (NBs) with a history of AFD. Methods: We conducted a cross-sectional study in full-term NBs of mothers with at least one perinatal, neonatal, or gasometric AFD antecedent. Neonatal morbidity was considered: if 1-min Apgar ≤ 6, or advanced neonatal maneuvers, or neonatal intensive care unit (NICU) admissions were necessary. The cutoff points were lactate > 4mmol/L and pH < 7.2. Results: Of 66 NBs, 33.3% of mothers presented at least one antecedent for developing AFD; 22.7% presented hypertensive pregnancy disease, 13.6% oligohydramnios, and 63.6% other factors. Perinatally, 28.7% required advanced neonatal resuscitation maneuvers and 7.5% admission to the NICU. In the gasometry, the lactate and pH values for the neonatal morbidity of the NBs' group were 4.726 ± 1.401 and 7.293 ± 0.056, respectively, versus 2.240 ± 0.318 and 7.359 ± 0.022 (p < 0.05) for the group without associated neonatal morbidity. Conclusions: Lactate values in the umbilical cord increased by 25%, and pH decreased by one percent in NBs with a history of AFD and associated morbidity.

Resumen Introducción: El sufrimiento fetal agudo (SFA) es una condición que amerita un diagnóstico oportuno debido a que genera hipoxia, acidosis e incluso la muerte intrauterina. El objetivo de este estudio fue determinar los valores de lactato y pH en cordón umbilical en recién nacidos de término con antecedente SFA. Métodos: Se llevó a cabo un estudio transversal, en recién nacidos a término, de madres que tuvieron al menos un antecedente para SFA de tipo perinatal, neonatal o gasométrico. Se consideró morbilidad neonatal cuando presentaron Apgar al minuto ≤ 6, o requirieron maniobras avanzadas de reanimación neonatal, o ingreso a Unidad de Cuidados Intensivos Neonatales (UCIN). El punto de corte fue > 4 mmol/L para los valores de lactato y pH < 7.2. Resultados: De un total de 66 recién nacidos, el 33.3% de las madres presentaron al menos un antecedente para desarrollar SFA; el 22.7% presentó enfermedad hipertensiva del embarazo, el 13.6%, oligohidramnios, y el 63.6%, otros factores. El 28.7% requirieron maniobras avanzadas de la reanimación neonatal y el 7.5%, el ingreso a la UCIN. En la gasometría, el valor de lactato y pH para el grupo de recién nacidos con morbilidad neonatal fue de 4.726 ± 1.401 y 7.293 ± 0.056 respectivamente, versus 2.240 ± 0.318 y 7.359 ± 0.022 (p < 0.05) para el grupo sin morbilidad neonatal asociada. Conclusiones: Se observó un incremento del 25% de los valores de lactato en cordón umbilical y una disminución del 1% del pH en los recién nacidos con antecedente de SFA y morbilidad asociada.

Analysis of pH, calcium ion release, and energy dispersive spectroscopy of a bioceramic root canal dressing

Abstract This study compared the pH and calcium ion release of calcium silicate- (Bio-C Temp) and calcium hydroxide-based (Ultracal XS) medications. Intracanal remnants of both medications were also evaluated using SEM-EDS after the removal protocol. Thirty-five bovine teeth were prepared. Fifteen were filled with Bio-C Temp and 15 with Ultracal XS. Five remained without intracanal medication (control group). Five samples from each experimental time (i.e.. 24, 72, and 168 hours) were used to measure pH and calcium ions release using a digital pH meter and microplate reader, respectively. Afterward, the peaks of the chemical elements composing both medications were analyzed in SEM-EDS. One-way ANOVA and Tukey's post hoc test analyzed the pH and calcium ion release data. Student's t-test compared the medications in each experimental time. SEM-EDS described the percentage of chemical elements in the samples. Bio-C Temp and Ultracal XS showed a significant pH increase from 24 to 168 hours (p<0.05). Ultracal XS showed a higher pH value at 24 hours than Bio-C Temp (p<0.05) but were similar at 72 and 168h (p > 0.05). Calcium ion release did not depend on the experimental period (p > 0.05). Bio-C Temp showed lower calcium ions release than Ultracal XS at 24 hours (p<0.05). SEM-EDS analyses showed the remains of both medications, but the concentration of Si, Al, and W ions was present only in the calcium silicate-based medication. Bio-C Temp presented alkaline pH and a satisfactory calcium ion release over the time. The remaining of both medications were present after the protocols for paste removal.

Resumo Este estudo comparou o pH e a liberação de íons cálcio de medicações intracanais a à base de silicato de cálcio (Bio-C Temp) e à base de hidróxido de cálcio (Ultracal XS). Remanescentes de ambas as medicações também foram avaliados usando microscopia eletrônica de varredura e espectroscopia de dispersão de energia após o protocolo de remoção. Trinta e cinco dentes bovinos foram preparados. Quinze dentes foram preenchidos com Bio-C Temp e 15 com Ultracal XS. Cinco permaneceram sem medicação intracanal (grupo controle). Cinco amostras de cada tempo experimental (ou seja, 24, 72 e 168 horas) foram usadas para medir o pH e a liberação de íons de cálcio usando um medidor de pH digital e um leitor de microplacas, respectivamente. Em seguida, os picos dos elementos químicos que compõem os dois medicamentos foram analisados ​​em microscopia eletrônica de varredura e por espectroscopia de dispersão de energia. Os testes One-way ANOVA e post hoc de Tukey analisaram os dados de pH e liberação de íons cálcio. O teste t de Student comparou as medicações em cada tempo experimental. A microscopia eletrônica de varredura e a espectroscopia de dispersão de energia descreveu a porcentagem de elementos químicos nas amostras. O Bio-C Temp e o Ultracal XS mostraram um aumento significativo de pH de 24 a 168 horas (p<0,05). O Ultracal XS apresentou um valor de pH mais alto em 24 horas do que o Bio-C Temp (p<0,05), mas foi semelhante em 72 e 168h (p > 0,05). A liberação de íons cálcio não dependeu do período experimental (p> 0,05). O Bio-C Temp apresentou menor liberação de íons de cálcio do que Ultracal XS em 24 horas (p<0,05). As análises de microscopia eletrônica de varredura e espectroscopia de dispersão de energia mostraram remanescentes de ambas as medicações, mas a concentração de íons Si, Al e W estavam presentes apenas na medicação à base de silicato de cálcio. O Bio-C Temp apresentou pH alcalino e maior liberação de íons cálcio. Remanescentes de ambas as medicações estiveram presentes após os protocolos de remoção da pasta.

Frequency of functional esophageal disorders in patients with refractory reflux symptoms in Lima, Peru

Gastroesophageal reflux disease (GERD) is a clinical condition in which gastric reflux causes symptoms or damage to the esophageal mucosa. It is managed with proton pump inhibitors, however, up to 45% of patients with suspected GERD are refractory to treatment. It is necessary to establish a true GERD diagnosis by means of a digestive endoscopy, which does not show lesions in approximately 70% of patients. In this scenario, it is necessary to perform an esophageal pH-impedance measurement, a procedure that allows to determine whether exposure to gastric acid is pathological. Of this group, patients with pathological acid exposure are diagnosed as true non-erosive reflux disease (NERD). If, in addition to not presenting esophageal lesions, they have a physiological exposure to gastric acid, they suffer from esophageal hypersensitivity or functional heartburn, which are functional disorders. These require a different approach from that of GERD or NERD, as the symptoms are not due to pathological exposure to gastric acid. The aim was to calculate the frequency of esophageal hypersensitivity and functional heartburn in patients with suspected NERD. This was a cross-sectional study. Data was collected by reviewing pH-impedance and manometry reports, 166 patients were selected. The frequency for functional disorders was 86.15%, being 46.9% for functional heartburn and 39.2% for esophageal hypersensitivity. The frequency of functional disorders was higher than that reported in previous studies. In conclusion, age, psychological conditions, dietary, cultural, ethnic or lifestyle factors inherent to our environment might play important roles in the development of functional disorders.

La enfermedad por reflujo gastroesofágico (ERGE) es una condición clínica en la que el reflujo gástrico provoca síntomas o daños en la mucosa esofágica. Se maneja con inhibidores de la bomba de protones; sin embargo, hasta el 45% de los pacientes con sospecha de ERGE son refractarios al tratamiento. Por lo cual, es necesario establecer un verdadero diagnóstico de ERGE mediante una endoscopia digestiva, que no muestra lesiones en aproximadamente el 70% de los pacientes. En este escenario, es necesario realizar una medición de pH-impedancia esofágica, procedimiento que permite determinar si la exposición al ácido gástrico es patológica. De este grupo, los pacientes con exposición patológica al ácido son diagnosticados como verdadera enfermedad por reflujo no erosiva (ERNE). Si además de no presentar lesiones esofágicas, tienen una exposición fisiológica al ácido gástrico, padecen hipersensibilidad esofágica o pirosis funcional, que son trastornos funcionales. Estos requieren un enfoque diferente al ERGE o ERNE, ya que los síntomas no se deben a una exposición patológica al ácido gástrico. El objetivo fue calcular la frecuencia de hipersensibilidad esofágica y pirosis funcional en pacientes con sospecha de ERNE. Este fue un estudio transversal. Los datos se recopilaron mediante la revisión de informes de pH-impedancia y manometría, se seleccionaron 166 pacientes. La frecuencia de trastornos funcionales fue de 86,15%, siendo 46,9% de pirosis funcional y 39,2% de hipersensibilidad esofágica. La frecuencia de trastornos funcionales fue superior a la reportada en estudios previos. En conclusión, la edad, las condiciones psicológicas, los factores dietéticos, culturales, étnicos o de estilo de vida inherentes a nuestro entorno podrían jugar un papel importante en el desarrollo de trastornos funcionales.

Assessment Of Groundwater Quality - A Case Study

The shortage and contamination of sources of surface water, as well as the increasing demand for agricultural practices, groundwater is important for many domestic, commercial, and industrial purposes. Human health and agricultural yields were significantly affected either by quality and concentration levels of groundwater. 25 groundwater samples were used in this study, which has been conducted in five different mandals of the Palnadu region. The samples were obtained from a variety of bore wells using the random sampling method, and the physical and chemical characteristics of water quality parameters were evaluated. The study covered the maximum amount of groundwater in the five mandals of Nuzendla, Vinukonda, Savalyapuram, Romicharla and Ipur as well as the suitable treatment methods for trying to turn the water in to the potable form.

A Study Of The Impact Of Economic Status On The Opinion Of Beneficiary Candidates Of The Scheme Of Developing High Quality Research About The Scheme Benefits

Continuous improvement and evolution in various fields are crucial to ensure a better living environment for everyone. To achieve this, researchers have a significant responsibility to produce valuable research in concerned areas. However, dedicated researchers often face various obstacles, such as financial stress, which can hinder their ability to conduct research. To support Ph.D. scholars, many central and state government funding agencies offer financial assistance schemes. In this regard, the Government of Gujarat has initiated a scheme called SHODH – ScHeme Of Developing High quality research to provide financial support to Ph.D. scholars from recognized universities/institutes of the state to produce quality research in various disciplines. However, it is essential to understand the impact of the scheme's benefits from the perspective of the beneficiary candidates, especially those belonging to different economic statuses. Therefore, a study has been conducted to explore the opinions of beneficiary candidates of the SHODH scheme about the scheme's selected aspects and whether their opinions differ based on their economic status. The study adopts a causal-comparative research method to gain insight into the requirements of research scholars belonging to different economic statuses. This information will enable better facilitation of scholars to produce meaningful research in their respective fields.

Historia de vida del Dr. C. Oscar B. Alonso Chil, ejemplo para la educación médica cubana / Life history of Ph.D. Oscar B. Alonso Chil, a role model for cuban medical education

Introducción: El Dr. C. Oscar B. Alonso Chil (1930-2021) formó parte de los médicos que permanecieron en Cuba después del triunfo de la Revolución. Fue fundador de servicios de asistencia en medicina interna y geriatría, y realizó importantes contribuciones a la docencia médica. Objetivo: Exponer la trayectoria de Oscar B. Alonso Chil como médico y docente de la medicina cubana revolucionaria, a través de su historia de vida. Métodos: Se realizó un estudio de tipo descriptivo y de corte cualitativo, donde se utilizó la técnica de la historia de vida, centrada en el aspecto profesional. Para ello se hizo una entrevista semiestructurada al testimoniante como fuente fundamental de información. Se validó el testimonio oral mediante la revisión de la documentación oficial en su expediente docente y la literatura científica existente relacionada con el tema, además de entrevistas a sus alumnos y compañeros de trabajo. Desarrollo: Se constató que fundó servicios; organizó la actividad docente; realizó tutorías, publicaciones y asesorías; y fue miembro de tribunales y consejos científicos. Cada una de sus actividades las desempeñó con gran compromiso e incondicionalidad a su profesión, lo cual le generó mucha satisfacción con la vida. Llegó a ostentar las más altas distinciones por su trabajo: Especialista de Segundo Grado en Medicina Interna, y Profesor Titular, Consultante y de Mérito de la Universidad de Ciencias Médicas de La Habana. Conclusiones: Oscar B. Alonso Chil contribuyó al desarrollo de la medina interna en Cuba en la etapa revolucionaria. Este profesor representa un modelo para los estudiantes de ciencias médicas por su prestigio profesional y científico(AU)

Introduction: Ph.D. Oscar B. Alonso Chil (b. 1930-d. 2021) was one of the physicians who stayed in Cuba after the triumph of the Revolution. He was a founder of the healthcare services for internal medicine and geriatrics, and made important contributions to medical teaching. Objective: To present the professional career of Oscar B. Alonso Chil as a physician and teacher of revolutionary Cuban medicine, through his life history. Methods: A descriptive and qualitative study was carried out, using the life history technique, focused on the professional aspect. For this purpose, a semistructured interview was conducted with the testimony witness as a fundamental source of information. The oral testimony was validated by reviewing the official documentation in his teaching file and the existing scientific literature related to the subject; in addition to interviews with his students and coworkers. Development: It was observed that he founded services, organized the teaching activity, supervised research, made publications and consultancies, and was a member of scientific boards and councils. He performed each of these activities with great commitment and unconditionality to his profession, which gave him great satisfaction with life. He achieved holding the highest distinctions for his work: second-degree specialist in Internal Medicine, as well as Full Professor, Faculty Consultant and Emeritus Professor of the University of Medical Sciences of Havana. Conclusions: Oscar B. Alonso Chil contributed to the development of internal medicine in Cuba during the revolutionary period. This professor represents a role model for students of medical sciences due to his professional and scientific prestige(AU)

Manejo endoscópico de la enfermedad por reflujo gastroesofágico (ERGE) / Endoscopic management of gastroesophageal reflux disease (GERD)

La enfermedad por reflujo gastroesofágico (ERGE) se manifiesta cuando el quimo gástrico refluye al esófago y pasa de ser fisiológico a sintomático y patológico. Es frecuente a nivel mundial y de difícil abordaje diagnóstico debido a la multitud de síntomas y presentaciones, haciendo que su enfoque terapéutico sea complejo. Existen múltiples opciones de tratamiento siendo el farmacológico basado en inhibidores de bomba de protones (IBP) la piedra angular. El manejo quirúrgico está descrito pero reservado a ciertos pacientes específicos. La terapia endoscópica surge como otra opción con indicaciones similares a la cirugía, pero con las ventajas propias de los procedimientos endoscópicos. Se han descrito varias técnicas endoluminales con pobres resultados, que no se han logrado popularizar.

Gastroesophageal reflux disease (GERD) occurs when gastric chyme refluxes back into the esophagus and changes from physiologic to symptomatic and pathologic. It is common worldwide and is difficult to diagnose due to the diversity of symptoms and presentations, making its therapeutic approach complex. Although there are multiple treatment options, proton pump inhibitors (PPIs) have been the mainstay of pharmacological management of GERD. Surgical treatment is described but is used in selected patients. Endoscopic therapy emerges as another option with similar indications as surgery, featuring the advantages of endoscopic procedures. Several endoluminal techniques have been described showing poor results, thus their generalized use has not been achieved.

Prevalence of oral injuries and salivary changes in patients with chronic renal failure on hemodialysis: systematic review and meta-analysis

The objective of this study was to evaluate whether individuals with chronic renal failure (CRF) undergoing hemodialysis treatment have more salivary and oral mucosa alterations when compared to healthy individuals, through a systematic review followed by meta-analysis. A systematic literature review was performed, evaluating randomized clinical trials found in the Proquest, Embase, Scopus, Cochrane Library, Web of Science, Lilacs and Pubmed databases, using MeSH terms and other keywords. Initially, 40 articles were included in the study and, after reading the complete articles, only 15 clinical trials that analyzed oral lesions and salivary changes in patients with CRF undergoing hemodialysis treatment were eligible. Most of the clinical studies included were cross-sectional and composed of a study group and a control group. The mean age of participants in the study group was 50.19 years and in the control group, 48.95 years. The most common oral alterations found in the CRF group in relation to the control group were xerostomia, uremic breath, dysgeusia, coated tongue, gingival bleeding and pale mucosa. The salivary flow of patients with CRF was 46.6% lower than the control group. The salivary pH in the study group was also more alkaline when compared to the control group. Greater amounts of urea, phosphate, C-reactive protein and total proteins were found in the saliva of individuals with CRF. Individuals with CRF undergoing hemodialysis are more prone to changes in both the quantity and quality of saliva, as well as having a greater amount of oral changes.

Determinants of time to viral clearance among SARS-CoV-2 infected individuals at Millennium COVID-19 care center in Ethiopia: A prospective observational study

Background: Understanding the COVID-19 disease course in terms of viral shedding is important to assist in providing a tailored isolation and treatment practice. Therefore, the current study aimed to estimate time to viral clearance and identify determinants among SARS-CoV-2 infected individuals admitted to Millennium COVID-19 Care Center in Ethiopia. Methods: A Prospective observational study was conducted among 360 randomly selected SARS-CoV-2 infected individuals who were on follow up from 2nd June to 5th July 2020. Kaplan Meier plots, median survival times, and Log-rank test were used to describe the data and compare survival distribution between groups. Association between time to viral clearance and determinants was assessed using the Cox proportional hazard survival model, where hazard ratio, P-value, and 95% CI for hazard ratio were used for testing significance Results: The Median time to viral clearance was 16 days. The log-rank test shows that having moderate and severe disease, one or more symptoms at presentation, and presenting with respiratory and constitutional symptoms seems to extend the time needed to achieve viral clearance. The Final Cox regression result shows that the rate of achieving viral clearance among symptomatic patients was 44% lower than patients who were asymptomatic (AHR=0.560, 95% CI=0.322-0.975, p-value=0.040). Conclusions: Presence of symptoms was found to be associated with delayed viral clearance implying that symptomatic patients are more likely to be infectious and therefore, attention should be paid to the practices regarding isolation and treatment of COVID-19 patients.

pH and GSH dual-responsive silybin nano-micelles for inhibition of breast cancer activity and metastasis in vitro / 药学学报

The clinical tumor therapy was greatly challenged due to the complex characteristics of tumor microenvironment, however, which also provide arena for novel therapeutic strategies. In this study, poly(2-ethyl-2-oxazoline)-poly(lactic acid)-SS-poly(β-amino ester (PEOz-PLA-SS-PBAE) triblock copolymers with pH and GSH double response were synthesized, polymer micelles were prepared by thin film hydration method for loading of silybin to improve its antitumor activity. The critical micelle concentration was determined by pyrene fluorescence method as 1.8 μg·mL-1. The particle size was 155.30 ± 1.80 nm as determined by dynamic light scattering, with polydispersity index of 0.168 ± 0.004. The drug loading and entrapment efficiency of the micelles were determined by HPLC as (5.48 ± 0.04)% and (68.52 ± 0.48)%, respectively. The in vitro drug release profiles showed that the micelles have low pH sensitivity and high GSH responsiveness, and exhibited sustained release profiles. The good biocompatibility of the material was proved by measuring the hemolysis rate and cytotoxicity of the blank micelle. The cytotoxicity and apoptosis rate of tumor cells showed that the drug loaded PEOz-PLA-SS-PBAE micelles had significant inhibitory effect and apoptosis-inducing effect on MDA-MB-231 cells. The results of wounding healing assay and Transwell invasion test showed that the drug loaded PEOz-PLA-SS-PBAE micelles could significantly inhibit the metastasis of MDA-MB-231 cells. The PEOz-PLA-SS-PBAE drug-loaded micelles prepared in this study have good inhibitory effect on tumor growth and anti-tumor metastasis in vitro, which lays the foundation for the further application of silybin.

Stability of human immunoglobulin(pH 4) for intravenous injection after process optimization / 中国生物制品学杂志

@#Objective To evaluate the stability of human immunoglobulin(pH 4)for intravenous injection(IGIV)after process optimization.Methods A filter plate and B filter membrane were used to filter the protein components in different separation stages to reduce the residue of immunoglobulin A(IgA)in the product in multi-batch large-scale production. The finished product was examined for the physical properties(appearance,visible foreign body,insoluble particle examination and thermal stability test)and the chemical properties[protein content,purity,molecular size distribution,titers of antiHBs,diphtheria antibody,prokallikrein activator(PKA),anti-complement activity(ACA),anti-A and anti-B hemagglutinin,and IgA residue]. The accelerated and long-term stability tests were performed.Results There was no significant difference in the key quality indicators between IGIV batches produced by the optimized process and the normal process,while the IgA residue decreased significantly(t = 3. 992 and 11. 215 respectively,each P < 0. 05). In the accelerated stability and long-term stability tests,all the test results of IGIV after process optimization were qualified,which met the relevant regulations in the third part of Chinese Pharmacopoeia(2020 edition).Conclusion IGIV after process optimization can effectively reduce IgA residue with good stability,which is of great significance for blood product manufacturers to improve the quality of IGIV products.

Prognostic analysis of 55 neonates with severe asphyxia / 预防医学

Objective@#To analyze the prognosis of neonates with severe asphyxia, so as to provide insights into improvements of prognosis among neonates with severe asphyxia. @*Methods@#Neonates with severe asphyxia born in Hangzhou Women's Hospital from 2016 to 2021 were recruited, and neonates' birth weight, gender, Apgar score, arterial blood pH value within 30 minutes after birth and maternal delivery data were collected. Outpatient follow-up was performed among neonates one year after birth, and the prognosis was evaluated with the Gesell Developmental Scale. Death or development quotient (DQ) of <75 was defined poor prognosis, and the clinical characteristics were compared between the good prognosis group and the poor prognosis group.@*Results@#A total of 55 neonates with severe asphyxia were enrolled, including 26 boys and 29 girls, with a median birth weight of 2 845.00 g (interquartile range, 1 948.00 g). There were 52 lying-in women (3 women had twins), with a mean age of (30.56±4.08) years, including 35 women with dystocia (67.31%) and 37 primiparas (71.15%). Of 55 neonates with severe asphyxia, there were 40 neonates with good prognosis (72.73%) and 15 neonates with poor prognosis (27.27%), including 13 deaths and 2 cases with DQ of <75. The incidence of abnormal fetal position was higher in the good prognosis group than in the poor prognosis group (36.84% vs. 0%; P<0.05), and the incidence of uterine torsion or uterine rupture was higher in the poor prognosis group than in the good prognosis group (21.43% vs. 0%; P<0.05). The median Apgar score at 5 min after birth and arterial blood pH within 30 min after birth were lower in the poor prognosis group [3.00 (interquartile range, 4.00) points and (6.93±0.23)] than in the good prognosis group [6.00 (interquartile range, 4.00) points and (7.23±0.15)] (P<0.05).@*Conclusion@#Maternal uterine torsion or uterine rupture, low Apgar score at 5 min after birth, and low arterial blood pH within 30 min after birth may aggravate the poor prognosis among neonates with severe asphyxia.

Glucuronic acid metabolites of phenolic acids target AKT-PH domain to improve glucose metabolism / 中草药·英文版

OBJECTIVE@#Phenolic acids widely exist in the human diet and exert beneficial effects such as improving glucose metabolism. It is not clear whether phenolic acids or their metabolites play a major role in vivo. In this study, caffeic acid (CA) and ferulic acid (FA), the two most ingested phenolic acids, and their glucuronic acid metabolites, caffeic-4'-O-glucuronide (CA4G) and ferulic-4'-O-glucuronide (FA4G), were investigated.@*METHODS@#Three insulin resistance models in vitro were established by using TNF-α, insulin and palmitic acid (PA) in HepG2 cells, respectively. We compared the effects of FA, FA4G, CA and CA4G on glucose metabolism in these models by measuring the glucose consumption levels. The potential targets and related pathways were predicted by network pharmacology. Fluorescence quenching measurement was used to analyze the binding between the compounds and the predicted target. To investigate the binding mode, molecular docking was performed. Then, we performed membrane recruitment assays of the AKT pleckstrin homology (PH) domain with the help of the PH-GFP plasmid. AKT enzymatic activity was determined to compare the effects between the metabolites with their parent compounds. Finally, the downstream signaling pathway of AKT was investigated by Western blot analysis.@*RESULTS@#The results showed that CA4G and FA4G were more potent than their parent compounds in increasing glucose consumption. AKT was predicted to be the key target of CA4G and FA4G by network pharmacology analysis. The fluorescence quenching test confirmed the more potent binding to AKT of the two metabolites compared to their parent compounds. The molecular docking results indicated that the carbonyl group in the glucuronic acid structure of CA4G and FA4G might bind to the PH domain of AKT at the key Arg-25 site. CA4G and FA4G inhibited the translocation of the AKT PH domain to the membrane, while increasing the activity of AKT. Western blot analysis demonstrated that the metabolites could increase the phosphorylation of AKT and downstream glycogen synthase kinase 3β in the AKT signaling pathway to increase glucose consumption.@*CONCLUSION@#In conclusion, our results suggested that the metabolites of phenolic acids, which contain glucuronic acid, are the key active substances and that they activate AKT by targeting the PH domain, thus improving glucose metabolism.

Regulation of pH on inflation and deflation of biosynthetic gas vesicles used as ultrasound molecular imaging probes / 生物工程学报

Gas vesicles (GVs) are gas-filled protein nanostructures that can regulate the buoyancy of microorganisms such as cyanobacteria and archaea. Recent studies have shown that GVs have the potential to be used as ultrasound molecular imaging probes in disease diagnosis and treatment. However, the mechanism of the inflation and deflation of GVs remains unclear, which hampers the preservation of GVs and gas replacement. In the present study, the environmental pH value was found to be an important factor in regulating the inflation and deflation of GVs. It can not only regulate the inflation and deflation of GVs in vivo to make Microcystis sp. cells present distinct levitation state, but also regulate the inflation and deflation of purified GVs in vitro, and the regulation process is reversible. Our results may provide a technical support for the large-scale production and preservation of biosynthetic ultrasound molecular imaging probes, especially for gas replacement to meet different diagnostic and therapeutic needs, and would facilitate the application of biosynthetic ultrasound molecular imaging probes.

Development of the method for determinating ADCC biological activity of IVIG / 中国输血杂志

【Objective】 To establish a method for determinating the antigen-dependent cell-mediated cytotoxicity (ADCC) of human immunoglobulin (pH4)for intravenous injection (IVIG) on luciferase reporter gene-modified cell assay. 【Methods】 As effector cells, Jurkat-NFAT-Luc-CD16 cells were used in the assay, and PLC/PRF/5 cells were used as target cells. After incubation of effector cells and target cells with IVIG, the method for determinating ADCC biological activity of IVIG was established by detecting luciferase released by activated T nuclear factor after binding of IVIG Fc fragment to effector cells. Meanwhile, the experimental assay conditions were optimized, and the methodology was verified subsequently. 【Results】 IVIG had a dose-response relationship in this method, which was consistent with four parameter logistic model. And the PLC/PRF/5 cells were finally determined as the target cells. The initial dilution concentration of antibody was 20 mg/mL, and the ratio dilution was 1∶2, and the effector to target ratio was 1∶3, and co-incubation time of two cells and IVIG was 24 hours. Within-run and between-run analysis including three independent tests, initial working concentration relative light unit (RLU) and the relative standard deviation (RSD) of the concentration for 50% of maximal effect(EC50) were less than 11%. The relative titers of the recovery samples of the two different dilution groups were (23.50±1.69)% and (49.30±2.97)%, respectively, and the corresponding recovery rates were (93.50±6.30)% and (96.24±5.43)%, respectively, with RSD less than 11%. 【Conclusion】 The method for determinating ADCC biological activity of IVIG based on luciferase reporter gene-modified cell assay was successfully established. It could be applied in determinating the ADCC biological activity of IVIG, and has the advantages of satisfactory linearity, accuracy, precision and specificity.

Hollow copper sulfide nanoparticles carrying ISRIB for the sensitized photothermal therapy of breast cancer and brain metastases through inhibiting stress granule formation and reprogramming tumor-associated macrophages

As known, the benefits of photothermal therapy (PTT) are greatly limited by the heat tolerance of cancer cells resulting from overexpressed heat shock proteins (HSPs). Then HSPs further trigger the formation of stress granules (SGs) that regulate protein expression and cell viability under various stress conditions. Inhibition of SG formation can sensitize tumor cells to PTT. Herein, we developed PEGylated pH (low) insertion peptide (PEG-pHLIP)-modified hollow copper sulfide nanoparticles (HCuS NPs) encapsulating the SG inhibitor ISRIB, with the phase-change material lauric acid (LA) as a gate-keeper, to construct a pH-driven and NIR photo-responsive controlled smart drug delivery system (IL@H-PP). The nanomedicine could specifically target slightly acidic tumor sites. Upon irradiation, IL@H-PP realized PTT, and the light-controlled release of ISRIB could effectively inhibit the formation of PTT-induced SG to sensitize tumor cells to PTT, thereby increasing the antitumor effect and inducing potent immunogenic cell death (ICD). Moreover, IL@H-PP could promote the production of reactive oxygen species (ROS) by tumor-associated macrophages (TAMs), repolarizing them towards the M1 phenotype and remodeling the immunosuppressive microenvironment. In vitro/vivo results revealed the potential of PTT combined with SG inhibitors, which provides a new paradigm for antitumor and anti-metastases.

Compound Tinglizi Decoction intervenes COPD-associated pulmonary hypertension through regulation of HMGB1-mediated pyroptosis and immune imbalance / 中国中药杂志

This paper aimed to investigate the effects of high mobility group box 1(HMGB1)-mediated pulmonary artery smooth muscle cell pyroptosis and immune imbalance on chronic obstructive pulmonary disease-associated pulmonary hypertension(COPD-PH) in rats and the intervening mechanism of Compound Tinglizi Decoction. Ninety rats were randomly divided into a normal group, a model group, low-dose, medium-dose, and high-dose Compound Tinglizi Decoction groups, and a simvastatin group. The rat model of COPD-PH was established by fumigation combined with lipopolysaccharide(LPS) intravascular infusion, which lasted 60 days. Rats in the low, medium, and high-dose Compound Tinglizi Decoction groups were given 4.93, 9.87, and 19.74 g·kg~(-1) Compound Tinglizi Decoction by gavage, respectively. Rats in the simvastatin group were given 1.50 mg·kg~(-1) simvastatin by gavage. After 14 days, the lung function, mean pulmonary artery pressure, and arterial blood gas of rats were analyzed. Lung tissues of rats were collected for hematoxylin-eosin(HE) staining to observe the pathological changes. Real-time fluorescent quantitative polymerase chain reaction(qRT-PCR) was used to determine the expression of related mRNA in lung tissues, Western blot(WB) was used to determine the expression of related proteins in lung tissues, and enzyme linked immunosorbent assay(ELISA) was used to determine the levels of inflammatory factors in the lung tissues of rats. The ultrastructure of lung cells was observed by transmission electron microscope. The forced vital capacity(FVC), forced expiratory volume in 0.3 second(FEV_(0.3)), FEV_(0.3)/FVC, peek expiratory flow(PEF), respiratory dynamic compliance(Cdyn), arterial partial pressure of oxygen(PaO_2), and arterial oxygen saturation(SaO_2) were increased, and resistance of expiration(Re), mean pulmonary arterial pressure(mPAP), right ventricular hypertrophy index(RVHI), and arterial partial pressure of carbon dioxide(PaCO_2) were decreased by Compound Tinglizi Decoction in rats with COPD-PH. Compound Tinglizi Decoction inhibited the protein expression of HMGB1, receptor for advanced glycation end products(RAGE), pro caspase-8, cleaved caspase-8, and gasdermin D(GSDMD) in lung tissues of rats with COPD-PH, as well as the mRNA expression of HMGB1, RAGE, and caspase-8. Pulmonary artery smooth muscle cell pyroptosis was inhibited by Compound Tinglizi Decoction. Interferon-γ(IFN-γ) and interleukin-17(IL-17) were reduced, and interleukin-4(IL-4) and interleukin-10(IL-10) were incresead by Compound Tinglizi Decoction in lung tissues of rats with COPD-PH. In addition, the lesion degree of trachea, alveoli, and pulmonary artery in lung tissues of rats with COPD-PH was improved by Compound Tinglizi Decoction. Compound Tinglizi Decoction had dose-dependent effects. The lung function, pulmonary artery pressure, arterial blood gas, inflammation, trachea, alveoli, and pulmonary artery disease have been improved by Compound Tinglizi Decoction, and its mechanism is related to HMGB1-mediated pulmonary artery smooth muscle cell pyroptosis and helper T cell 1(Th1)/helper T cell 2(Th2), helper T cell 17(Th17)/regulatory T cell(Treg) imbalance.