Isotemporal substitution analysis of time between sleep, sedentary behavior, and physical activity on depressive symptoms in older adults: a cross-sectional study

ABSTRACT BACKGROUND: Compared to young individuals, older adults participate more in sedentary behavior (SB) and less in physical activity (PA). These behaviors are associated with numerous adverse health factors. OBJECTIVE: The purpose of the study was to examine the hypothetical effects of substituting time spent sleeping, performing SB, and performing moderate-to-vigorous physical activity (MVPA) on depressive symptomatology in older adults. DESIGN AND SETTING: An analytical cross-sectional study employing exploratory survey methods was conducted in the city of Alcobaça in the state of Bahia, Brazil METHODS: The study included 473 older adults who answered a structured questionnaire during an interview. Exposure time to SB and PA level were assessed using the International Physical Activity Questionnaire, and depressive symptoms were analyzed using the short version of the Geriatric Depression Scale. An isotemporal replacement model was used to evaluate the effects of different SB sessions on depressive symptomatology. RESULTS: An increase in the risk of depressive symptoms was observed when MVPA and sleep time were substituted for the same SB time at all times tested, with maximum values of 40% and 20%, respectively. Opposite substitution of MVPA and sleep time increments reduced the risk of depressive symptomatology by 28% and 17%, respectively. CONCLUSIONS: The results of the present study indicate that replacing SB with the same amount of sleep or MVPA may reduce depressive symptoms. The longer the reallocation time, the greater are the benefits.

The Status and Trends of Food Fraud in Tamale, Ghana

Despite its seriousness, food fraud has not received the necessary attention in Ghana’s discourse on food safety. Food fraud is generally considered as the intentional misrepresentation of the contents or identity of food for economic gain. The study was aimed at assessing the food fraud awareness level of participants as well as the foods most likely to be implicated in food fraud cases in Tamale, Ghana. Data was collected from 385 participants, including food business operators and consumers, via a simple random sampling technique using a structured questionnaire. Most participants (54%) were not aware of food fraud and its related activities before the study. Beverages and juices, fruits and vegetables, spices, oils, meat and fish, baked foods, honey, milk, and semi-processed local foods such as groundnut paste, "Dawadawa," “Kulikuli zim,” and “Agushi powder” were all revealed to be implicated in food fraud by respondents. Adulteration was the most common food fraud action, but tampering, substitution, and mislabeling were also identified as ongoing in the study area. “Moora” (Bixa orellana seeds) was revealed as the key adulterant used in most foods. Food fraud, which is a threat to consumer health and well-being, is active in the region and is predicted to increase without strict regulation and increased sensitization about its dangers. The fight against food fraud should be refocused on making food defense systems like vulnerability analysis and critical control points (VACCP) a key aspect of food safety systems to tackle food fraud.

Medicamentos genéricos ¿buenos y usables? La percepción de los estudiantes de medicina en un estado mexicano

Introducción: el conocimiento y la percepción hacia los medicamentos genéricos son temas que surgen como un factor importante a explorar en los estudiantes de medicina. Objetivo: determinar las diferencias entre los estudiantes de medicina de universidades públicas y privadas sobre la percepción y el uso de las Especialidades Farmacéuticas Genéricas (EFG). Materiales y métodos: se realizó un estudio cuantitativo de tipo observacional, transversal, analítico y comparativo en un universo de 858 estudiantes matriculados durante 2019-2020 en cinco escuelas de medicina del estado mexicano de Tabasco. A través de Google Forms se recolectaron los datos de un formulario auto aplicado con base a un cuestionario previamente validado. Se emplearon estadísticas descriptivas para evaluar las percepciones de los estudiantes y pruebas no paramétricas a través de un modelo de análisis de diferencia de medias para comparar el resultado entre las universidades. Resultados: la percepción de las dimensiones de calidad (8= 12,51) y eficacia (8=6,06) muestran una postura indecisa en general. En la fiabilidad (8=6,99), los alumnos estuvieron de acuerdo. Las dimensiones de preferencia-experiencia (8=10,649) y la de accesibilidad (X=7,01), colocan a los alumnos en el grupo de indecisos. En la comparación de medias de la escala de percepción de EFG (prueba t de estudent), la universidad pública presentó una media baja (8=24,72), mientras que en el grupo de universidades privadas fue mayor (8=26,06). En cuanto al uso de EFG, la universidad pública presentó una media 8=38,22, mientras que el grupo de universidades privadas fue menor (8=36,70). Conclusiones: se requiere incluir en los contenidos curriculares de los futuros profesionales de la medicina, mayor información sobre calidad, seguridad y eficacia de las EFG, lo que contribuirá a elevar el nivel de confianza en su prescripción.

Introduction: Knowledge and perception towards generic drugs are topics that emerge as an important factor to explore in medica students. Objective: To determine the differences between medical students from public and private universities on the perception and use of Generic Pharmaceutical Specialties (GFE). Materials and methods: A quantitative observational, cross-sectional, analytica and comparative study was conducted in a universe of 858 students enrolled during 2019-2020 in five medical schools in the Mexican state of Tabasco. Through Google Forms, data were collected from a self-applied form based on a previously validated questionnaire Descriptive statistics were used to assess student perceptions, and nonparametric tests through an analysis model for difference of means to compare the result between universities. Results: The perception of the dimensions of quality (8= 12,51) and efficacy (8=6,06) shows an indecisive position in general. On reliability (8=6,99), students agreed. The dimensions of preference-experience (8=10.649) and accessibility (8=7,01), place students in the group of undecideds. In the comparison of means of the GFE perception scale (student's t test), the public university presented a low mean (8=24,72), while in the group of private universities it was higher (8=26,06). Regarding the use of GFE, the public university presented a mean 8=38,22, while the group of private universities was lower (8=36,70). Conclusions: It is necessary to include in the curricular contents of future medical professionals more information on quality, safety and efficacy of GFE, which will contribute to raising the level of confidence in their prescription.

Study of antidiabetic activity of two novel Schiff base derived dibromo and dichloro substituted compounds in streptozotocin-nicotinamide-induced diabetic rats: pilot study

Abstract Schiff bases are aldehyde-or ketone-like chemical compounds in which an imine or azomethine group replaces the carbonyl group. Such compounds show various beneficial biological activities, such as anti-inflammation and antioxidants. The present study addresses comprehensiveevaluation of antidiabetic effect of two novel dibromides and dichlorides substituted Schiff bases substituted Schiff bases (2,2'-[1,2-cyclohexanediylbis (nitriloethylidyne)]bis[4-chlorophenol] (CNCP) and 2, 2'-[1,2-cyclohexanediylbis(nitriloethylidyne)]bis[4-bromophenol] (CNBP) with two different doses, high (LD) and low (LD) in streptozotocin and nicotinamide induced diabetic rats. The rats were separated into normal, untreated, treated and reference groups. Except for the normal group, diabetes traits were induced in the rest animals. Insulin level was measured, and the effect of the compounds on biochemical parameters of liver function and lipid profile were evaluated. High glucose and decreased insulin level are observed in the groups. The histological evaluation confirms that the hepatic architecture in the treated animals with a low dose of CNCP is quite similar to that of the normal hepatic structure and characterized by normal central vein, hepatocytes without any fatty alterations and mild red blood cell infiltration. CNCP (LD) and CNBP (HD) are more successful in enhancing cell survival in the diabetic rat's liver and can be responsible for causing much healthier structure and notable morphology improvement.

Component analysis of relationship between 24 hour movement behavior and physical fitness in college students / 中国学校卫生

Objective@#To explore the relationship between 24 hour movement behavior and physical fitness in college students, so as to provide a reference for physical fitness interventions for college students.@*Methods@#A survey was conducted from September 23 to November 12, 2022, involving 342 college students selected from one comprehensive college among Shanghai City, Hubei Province and Zhejiang Province. Accelerometers were used to measure 24 hour movement behavior, and programs specified in the National Physical Fitness Standards for Students (2014 revision) were used to evaluate physical fitness. Compositional linear regression was used to analyze the association between 24 hour movement behavior and physical fitness. The effects of compositional isotemporal substitution of 24 hour movement behavior on physical fitness were also examined.@*Results@#The geometric means for sleep, sedentary behavior, light physical activity (LPA), and moderate to vigorous physical activity (MVPA) were 515.89, 678.88 , 196.30, 48.92 min/d, respectively, and the comprehensive physical fitness score was (73.09±8.55). The proportion of participants who passed the fitness test was 72.51%. Overall, 20.76% had excellent or good scores, whereas 6.73% failed. Compositional linear regression indicated that physical fitness was significantly positively associated with MVPA ( β =2.55) and LPA ( β = 5.88 )( P <0.05), but no significantly associated with sleep ( β =-5.18) and sedentary behavior ( β =-3.24)( P >0.05). Isotemporal substitution indicated that reallocation of 15 minutes from sleep and sedentary behavior to MVPA resulted in a 0.71 and 0.64 point increase in physical fitness, respectively. Similarly, reallocating the same duration to LPA led to a 0.50 and 0.43 point increase in physical fitness, respectively. Dose response analysis revealed that the mutual substitution of LPA with sedentary behavior and sleep had symmetry, whereas the mutual substitution of MVPA with sedentary behavior and sleep had asymmetry. The effectiveness of replacing sleep or sedentary behavior with MVPA in improving physical fitness decreased with increasing allocation time, whereas the adverse effects of replacing MVPA with sleep or sedentary behavior increased with increasing allocation time.@*Conclusion@#In the context of 24 hour movement behavior, increasing the time spent on LPA and MVPA is beneficial for physical fitness among college students. It should be recommend that college students actively transition from sedentary behavior to engaging in physical activity, with a particular emphasis on incorporating MVPA.

The relationship between behavior isotemporal substitution and depression among vocational school students with different moderate-to-vigorous physical activity durations / 中国学校卫生

Objective@#To explore the relationship between isotemporal substitution of 10 min/d of vigorous physical activity (VPA), moderate physical activity (MPA), walking, sedentary behavior (SB) and sleep (SLP) and depression among vocational school students with different duration of moderate-to-vigorous physical activity (MVPA), so as to provide time allocation suggestions for reducing depression levels.@*Methods@#The convenient cluster sampling method was adopted to conduct a questionnaire survey among 8 149 grade one to grade three students in 14 vocational schools in Shanghai and Jiangsu Province from December 2021 to January 2022. According to whether the MVPA reached 60 min/d, the vocational school students were divided into the MVPA standard group and the MVPA non-standard group, and the isotemporal substitution model was used for analysis.@*Results@#About 19.81% of students were in the MVPA standard group. In the MVPA non-standard group, substituting MPA for all other studied behaviors and substituting SLP for walking and SB were negatively correlated with depression ( β =-0.78, -0.90, -0.88, -0.83; -0.07 , -0.05, P <0.05), and the association of MPA substitution was much greater than that of SLP substitution. In the MVPA standard group, replacing VPA, walking and SB with SLP were all negatively associated with depression ( β =-0.23, -0.12, -0.10 ), whereas replacing MPA, SB and SLP with VPA was all positively associated with depression ( β =0.15, 0.13, 0.23) ( P <0.05).@*Conclusion@#The MVPA level of vocational school students is low. The effects of isotemporal substitution for VPA and MPA are different when MVPA duration is up to standard and when MVPA duration is not up to standard. Appropriate time allocation suggestions should be provided based on the characteristics of adolescents with different MVPA durations.

The isochronous substitution effect of 24 hour activity behavior on physical health of college students / 中国学校卫生

Objective@#An isochronous substitution model was established to explore the association and substitution effect between college students 24 hour activity behavior and physical health, so as to provide specific activity behavior suggestions for college students to improve their physical health.@*Methods@#A stratified random cluster sampling method was used to conduct physical fitness tests and 24 hour activity behavior surveys among 2 794 college students in 12 colleges and universities in Tianjin.Time spent on sedentary behavior(SB), light intensity physical activity(LPA), moderate to vigorous physical activity(MVPA) and sleep(SLP) time. The isochronous method of components was used to explore the relationship between 24 h activity behavior and physical health.@*Results@#Except for 50 m running, MVPA was negatively correlated with BMI Z ( β =-0.62, P <0.05), but positively correlated with other physical fitness indexes ( β =0.34~274.23, P <0.05). LPA was not associated with lung capacity, sitting forward flexion and 50 m running, and negatively correlated with other physical fitness indexes ( β =-14.30- -0.19, P <0.05). SB was negatively correlated with most physical fitness indexes ( β =-11.57- -0.33, P <0.05), but positively correlated with BMI Z ( β =0.45, P < 0.05 ). In addition to lung capacity, SLP was positively correlated with BMI Z , total physical fitness score,1 minute sit-ups, pull ups, 800/1 000 m running, sitting forward flexion, and 50 m running ( β =0.27-11.21, P <0.05), but negatively correlated with long jump ( β =-0.10, P <0.05）. Isochronous substitution showed that the adverse effects of 30 min/d SB and LPA substitution of MVPA were much greater than the beneficial effects of MVPA substitution for corresponding behaviors (total physical score: SB, -0.58 vs 0.47 points; LPA, -0.50 vs 0.38 points).@*Conclusion@#MVPA and SLP have been found to have a positive effect on physical fitness among college students. Therefore, in the process of improving the physical health of college students, ensuring adequate sleep, improving MVPA and reducing SB as much as possible may be one of the effective methods.

A case of recurrent ureteral terminal tumor after radical cystectomy and rectal bladder replacement / 中华泌尿外科杂志

For invasive bladder cancer, radical cystectomy and rectal substitution for sigmoid skin fistulas were commonly used in some medical centers. There is no report on the feasibility of sigmoid colon retraction except nephroureterectomy for patients with recurrent ureteral tumors after operation. We presented a case of recurrent ureteral tumors after rectal substitution bladder surgery for bladder cancer. Finally, left ureteral resection + sigmoid colon return + right ureteral skin stoma was successfully performed.The patient was followed up for 1 year without recurrence.

Substitution mode of rare and endangered Chinese medicinal materials and research strategy of multi-component replacement / 中国中药杂志

Rare and endangered Chinese medicinal materials are the material basis for innovation and development of Chinese medicinal materials and their curative effects are remarkable. However, the resources are in shortage due to various man-made or natural factors such as rising demand, overexploitation and environmental degradation. Therefore, finding alternatives is a feasible and effective solution. This study systematically sorted out the list of rare and endangered Chinese medicinal materials, and combed relevant policies and regulations. According to existing research, the substitution model of rare and endangered Chinese medicinal materials was constructed from the theoretical level. In view of the slow search for substitutes, the failure to follow the basic theory of traditional Chinese medicine in the process of research and development, the difficulty in breaking through technologies and the incomplete guarantee of the clinical efficacy of substitutes, a multi-component replacement was proposed to replace the originals with more effective components from a wide range of sources. This study was expected to promote the study on the substitutes of rare and endangered Chinese medicinal materials to step into a new stage.

Serological Characteristics of Subtype A Caused by New A Allele Mutation and a Family Survey / 中国实验血液学杂志

OBJECTIVE@#In this study, the results of forward and reverse blood typing of a male patient diagnosed as bronchiectasis were inconsistent, which were type O and type A respectively. Multiple experiments including genotyping and sequencing and family investigation were carried out to determine the subtype of ABO blood group and explore the serological characteristics of this subtype.@*METHODS@#Standard serological techniques were used to conduct forward and reverse typing, reverse blood typing enhancement test, H antigen identification, absorption-elution test, salivary blood group substances test, and PCR-SSP method for ABO genotyping and exon 6 and 7 sequencing.@*RESULTS@#The proband's blood group was type O by forward typing, but antigen A could be detected by absorption-elution test, anti-A1 could be detected by reverse blood typing enhancement test, it was found that there was substance H but no substance A in saliva, and the serological characteristics were consistent with Ael subtype. Gene sequencing analysis showed that there was a c.625T>G base substitution on the basis of A102, which had never been reported before. Family survey showed that c.625T>G base substitution appeared in three generations of the family.@*CONCLUSION@#In this study, a new subtype A with Ael serological characteristics caused by c.625T>G mutation was identified. c.625T>G base substitution results in the weakening of A antigen, and this mutation can be stably passed down to future generations.

A non-toxic recombinant protein rSUMO-CPBm4 as a potential vaccine candidate against Clostridium perfringens type C beta enterotoxemia

@#Beta toxin (CPB) is a lethal toxin and plays a key role in enterotoxemia of ruminants caused by Clostridium perfringens type C strain. The existing vaccines based on crude CPB need time-consuming detoxification and difficult quality control steps. In this study, we synthesized the rCPBm4 of C. perfringens type C strain and small ubiquitin-like modifier (SUMO)-tag CPBm4 (rSUMO-CPBm4) by introducing four amino acid substitutions: R212E, Y266A, L268G, and W275A. Compared with rCPBm4, rSUMO-CPBm4 was expressed with higher solubility in Escherichia coli BL21 (DE3). Neither rCPBm4 nor rSUMO-CPBm4 was lethal to mice. Although rCPBm4 and rSUMO-CPBm4 were reactogenic with polyclonal antibodies against crude CPB, rabbits vaccinated with rSUMO-CPBm4 developed significant levels of toxin-neutralizing antibody (TNA) titers that conferred protection against crude toxin challenge. These data suggest that genetically detoxified rSUMO-CPBm4 is a promising subunit vaccine candidate for C. perfringens type C beta enterotoxemia.

Interpretation and consideration of “Substitution of in vivo method(s) by in vitro method(s) for the quality control of vaccines” in General Texts of European Pharmacopoeia / 中国生物制品学杂志

Interpretation and consideration of “Substitution of in vivo method(s) by in vitro method(s) for the quality control of vaccines” in General Texts of European Pharmacopoeia@#Potency is a critical quality attribute for controlling relevant biological properties and batch consistency of vaccines.The methods can be divided into in vivo and in vitro methods according to whether animals are used.The in vivo methods are large consuming of animals and time,as well as have large variant detection results.In contrast,the in vitro alternative methods have been the hotspot of research due to their simple operations,in line with 3Rs principles,and more stable results.However,owing to the complexity of experimental design and the lack of corresponding guidance,the research progress of alternative methods is slow.Recently,“Substitution of in vivo method(s) by in vitro method(s) for the quality control of vaccines” was adopted in the European Pharmacopoeia(10th Edition),which clarifies the critical points of consideration for substitution.This paper interprets the chapter and puts forward some thoughts on that in China,which is expected to speed up the alternative methods research and improve the ability of vaccine quality control and supervision in China.

Relationship between 24 hour movement behavior and obesity indicators in children and adolescents / 中国学校卫生

Objective@#The method of compositional data analysis was used to explore the relationship between 24 hour movement behavior and obesity indicators, and to examine the difference of quantitative effect on obesity indicators when one behavior replaced another behavior, so as to provide specific movement behavior advice for weight control in children and adolescents.@*Methods@#In June 2021, 231 students from eight classes in a primary school and a middle school in Taiyuan City, Shanxi Province were voluntarily recruited by using random cluster sampling. ActiGraph GT3X+ accelerometer was used to measure 24 hour movement behavior and Inbody J20 body composition analyzer was used to measure body composition. The relationship between each component and obesity indicators was analyzed by compositional multivariate linear regression model. In addition, 30 minutes of one behavior was used to replace another behavior to predict the effect difference of the outcomes.@*Results@#After adjusting for covariates such as height, weight, age, and sex, compared with time spent in sedentary behavior(SB), sleep (SLP) and light physical activity (LPA), time spent on moderate to vigorous physical activity (MVPA) was positively correlated with fat free mass index (FFMI) ( β= 0.40, P ＜0.05), negatively correlated with waist circumference (WC) ( β=-2.50, P ＜0.05) and waist hip ratio (WHR) ( β= -0.04 , P ＜0.05). Compared with SB, SLP and MVPA, time spent on LPA was positively correlated with WHR ( β=0.06, P < 0.05 ). If MVPA of 30 min/d replaces SLP, SB, and LPA respectively, WC and WHR decrease 1.10,1.10,1.34 cm and 0.02, 0.02 ,0.02 respectively, and FFMI increases 0.19,0.19,0.15 kg/m 2 respectively.@*Conclusion@#In 24 h movement behavior, with consistent level of sedentary behavior, sleep or low intensity movement behavior, maintaining a high level of MVPA and replacing sedentary with active activities are crucial for optimal abdominal fat and fat free mass in children and adolescents.

Relationship between 24 hour movement behavior and physical fitness among pupils / 中国学校卫生

Objective@#To examine the relationship between 24 hour movement behavior and physical fitness of pupils by using compositional analyses, so as to provide a theoretical basis for physical activity promotion and physical fitness improvement.@*Methods@#By random cluster sampling method, 120 students of grade 4 and 5 from the Second Experimental Primary School of Yingze District of Taiyuan were selected. Physical fitness was evaluated by the indicators of the Protocol of National Physical Training Standard and 20 meter shuttle run. The movement behavior was measured by accelerometer. The relationship between each behavior and physical fitness was analysed by component multiple linear regression, and the effect of replacement of components on physical fitness was discussed.@*Results@#Girls 1minute situps were lower than boys（24.79±7.77，28.21±6.52），and sitting forward flexion was higher than boys[9.00（5.00，14.00），5.20（1.00，9.75）cm]（ t/Z =2.60，-3.15， P ＜0.05）. Boys showed higher light physical activity(LPA), moderate to vigorous physical activity(MVPA) and lower sedentary behavior(SB), while girls showed lower LPA, MVPA and higher SB. MVPA was positively correlated with the performance of 30 second rope skipping and 20 meter shuttle run ( β= 13.19, 7.90, P <0.05). Sleep(SLP), SB, and LPA were not significantly correlated with physical fitness. After re allocating 10 min MVPA to SB and SLP，the performance of 30 second rope skipping and 20 meter shuttle run increased by 2.25，2.28 and 1.28 ,1.34 times，respectively，while significantly decreased after reverse reallocation ( P <0.05). MVPA replaced LPA，the 20 meter shuttle run performance increased 1.46 times，while decreased significantly in reverses ( P <0.05).@*Conclusion@#MVPA is positively correlated with the speed and endurance of pupils. There are gender differences in movement behavior patterns and physical fitness. Children, especially girls, should be encouraged to raise exercise awareness and increase PA, especially MVPA.

Diagnosis and treatment of dyspepsia associated with pancreatic tumors / 临床肝胆病杂志

Dyspepsia is the one of the most common clinical manifestations of digestive system diseases and has various and complex causes， among which pancreatic tumor is a relatively uncommon cause and is easily neglected in clinical practice. The dual factors of tumor and dyspepsia may cause a significant reduction in the quality of life of patients. At present， there is still a lack of standardized diagnosis and treatment strategies for dyspepsia associated with pancreatic tumors， and this article reviews the diagnosis and treatment of this disease.

Establishment of an intervention model for adolescent obesity based on component isochronous substitution method / 中国学校卫生

Objective@#To explore the relationship between isochronous substitution and BMI, waist circumference (WC), and body fat rate (FAT) among physical activity (PA), sedentary (SB), and sleep (SLP), so as to provide effective measures for obesity control in adolescents.@*Methods@#A total of 193 adolescents aged 12-15 (90 males and 103 females) was randomly selected, and their height, weight, and BMI were measured using routine testing methods from May to August 2022. The PA, SB and SLP of the participants were measured using a 3D accelerometer (ActiGraph GT3X+).@*Results@#The arithmetic mean value overestimated SLP (40.8%) and SB (39.6%) to some extent, and underestimated LPA (16.1%) and MVPA (3.5%) to some extent. Based on the ISM at 15 min, MVPA was substituted for other activity, BMI Z decreased by 0.17-0.22 units, WC Z decreased by 0.16-0.20 units, and FAT Z decreased by 0.17-0.22 units. The substitution between MVPA and for other activity exhibited significant asymmetry. The effects of MVPA substitutions for SB was the largest, followed by the effects of MVPA substitutions for SLP, and the effects of MVPA substitutions for LPA was the lowest. As MVPA substitutions for other behaviors, it reached its maximum (0.06-0.08 units ) when the MVPA time increased by 5 minutes.@*Conclusions@#MVPA plays an irreplaceable role in the control of adolescent obesity . While reducing SB time, MVPA duration should be increased to ensure that the daily MVPA duration is not less than 55 minutes in order to effectively control obesity.

Influencing factors for direct-acting antiviral therapy failure in treatment of hepatitis C / 临床肝胆病杂志

Objective To investigate the influencing factors for direct-acting antiviral agent (DAA) therapy failure in the treatment of hepatitis C by comparing baseline clinical data and resistance-associated substitution (RAS) in sequencing data between the patients with HCV RNA reactivation after DAA therapy and the patients with successful DAA treatment. Methods A total of 13 patients from multiple centers who failed DAA therapy from November 2019 to October 2021 were enrolled as treatment failure group, and sequencing was performed for their positive serum samples. A total of 51 patients with successful DAA treatment were enrolled as control group, and baseline clinical data and sequencing results were compared between the treatment failure group and the control group. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups, and the chi-square test was used for comparison of categorical data between groups; univariate and multivariate logistic regression analyses were performed to calculate odds ratio ( OR ) and investigate the influencing factors for treatment failure. Results All 12 patients with complete treatment data experienced recurrence within 1 year after the end of medication. The male patients with treatment failure had significantly higher baseline total bilirubin, direct bilirubin, and creatinine than their female counterparts ( Z =-2.517, -2.440, and -2.132, P =0.010, 0.010, and 0.038), and the patients with an age of ≤55 years ( OR =5.152, 95% confidence interval [ CI ]: 1.116-23.790, P =0.036) or genotype 3b ( OR =9.726, 95% CI : 1.325-71.398, P =0.025) had a higher probability of treatment failure. There were differences in the incidence rates of major RAS mutations on three gene fragments between the treatment failure group and the treatment success group, and the common RAS mutations detected in the treatment failure group were not detected in the treatment success group. Conclusion Age, genotype, and RAS in serum virus gene sequence are influencing factors for DAA treatment failure.

Evaluation of the rationality and feasibility of the grouping method for centralized procurement of insulin drugs in Wuhan based on the results of questionnaire survey among endocrinology physicians / 中国药房

OBJECTIVE To investigate t he attitude of endocrinology physicians to clinical conversion and substitution of insulin drugs ，and to provide basis for improving the centralized procurement program of insulin. METHODS The proportion of convertible and substitutable insulin recognized by endocrinology physicians was investigated by questionnaire from 4 dimensions： intergenerational level ，bargaining group level ，common name level and brand/specification level. The subjects were endocrinology physicians in the third grade class A general hospitals in Nanchang. RESULTS A total of 89 questionnaires were successfully distributed，accounting for 80.2％ of the on-the-job endocrinology physicians （111 in total ）in the third grade class A general hospitals in Nanchang. Eighty-nine questionnaires were collected ，one of which was invalid ，and the effective rate was 98.9％. At the intergenerational level ，93.2％ of endocrinology physicians preferred insulin analogues. At the bargaining group level ，the weighted average of the convertible ratio between group 3 and group 4 approved by physicians was 63.9％. At the levels of common name and brand/specification ，the weighted averages of convertible proportion of each group were more than 70％. CONCLUSIONS The method of insulin grouping in Wuhan is reasonable which can complete clinical conversion and substitution of insulin in the group safely. It is suggested to cancel long-acting human insulin group. The weighted average of the proportion of convertible and substitutable drugs in the group is high. It is suggested to increase the agreed purchase volume of insulin and conduct“volume price linked ”negotiations. When the surveyed physicians choose the initial treatment scheme of insulin ，they pay more attention to the factors such as efficacy and safety ，so the replacement of insulin should be based on the clinical efficacy and drug safety.

Analgesia with blockage of the erector plane of the spine in the postoperative period of cardiac surgery. Case report / Analgesia pós-operatória em cirurgia cardíaca pelo bloqueio do plano eretor da espinha. Relato de caso

ABSTRACT BACKGROUND AND OBJECTIVES: Persistence of pain in the postoperative thoracic region is very common with conventional analgesia performed only with opioids, which prolongs recovery, increasing costs and morbidity. Erector spinae plane blockage is a promising technique for the analgesic control in the postoperative period of cardiac surgeries. The purpose of this study was to describe a case in which erector spinae plane blockage provided adequate postoperative analgesic control. CASE REPORT: A 61-year-old male patient submitted to elective cardiac surgery for left ventricular aneurysmectomy and coronary artery bypass grafting. On the first postoperative day presented pain of intensity 8 on the visual analog scale in the left hemithorax. The patient underwent erector spinae plane blockage with a catheter located at T5 guided by ultrasound with a 17G Tuohy needle and injection of 20mL of 0.5% ropivacaine providing important decrease and improvement of pulmonary expansibility. CONCLUSION: Erector spinae plane blockage provided adequate analgesia and was considered a good therapeutic option.

RESUMO JUSTIFICATIVA E OBJETIVOS: A persistência da dor na região torácica no pós-operatório é muito comum com analgesia convencional realizada apenas com opioides, o que prolonga a recuperação, aumentando os gastos e a morbidade. O bloqueio do plano eretor da espinha é uma técnica promissora no controle analgésico no pós-operatório das cirurgias cardíacas. O objetivo deste estudo foi descrever um caso em que o bloqueio do plano eretor da espinha propiciou adequado controle analgésico pós-operatório. RELATO DO CASO: Paciente do sexo masculino, 61 anos, submetido à cirurgia cardíaca eletiva de aneurismectomia do ventrículo esquerdo e revascularização do miocárdio. No primeiro dia de pós-operatório apresentou dor de intensidade 8 pela escala analógica visual em hemitórax esquerdo. Foi submetido ao bloqueio do plano eretor da espinha com cateter locado em T5 guiado por ultrassom com agulha Tuohy 17G e injeção de 20mL de ropivacaína a 0,5%, propiciando importante diminuição e melhora da expansibilidade pulmonar. CONCLUSÃO: O bloqueio do plano eretor da espinha promoveu analgesia adequada, sendo considerado como uma boa opção terapêutica.

CRISPR-mediated base editing in mice using cytosine deaminase base editor 4

BACKGROUND: Many human genetic diseases arise from point mutations. These genetic diseases can theoretically be corrected through gene therapy. However, gene therapy in clinical application is still far from mature. Nearly half of the pathogenic single-nucleotide polymorphisms (SNPs) are caused by G:C>A:T or T:A>C:G base changes and the ideal approaches to correct these mutations are base editing. These CRISPR-Cas9-mediated base editing does not leave any footprint in genome and does not require donor DNA sequences for homologous recombination. These base editing methods have been successfully applied to cultured mammalian cells with high precision and efficiency, but BE4 has not been confirmed in mice. Animal models are important for dissecting pathogenic mechanism of human genetic diseases and testing of base correction efficacy in vivo. Cytidine base editor BE4 is a newly developed version of cytidine base editing system that converts cytidine (C) to uridine (U). RESULTS: In this study, BE4 system was tested in cells to inactivate GFP gene and in mice to introduce single-base substitution that would lead to a stop codon in tyrosinase gene. High percentage albino coat-colored mice were obtained from black coat-colored donor zygotes after pronuclei microinjection. Sequencing results showed that expected base changes were obtained with high precision and efficiency (56.25%). There are no off-targeting events identified in predicted potential off-target sites. CONCLUSIONS: Results confirm BE4 system can work in vivo with high precision and efficacy, and has great potentials in clinic to repair human genetic mutations.