Preparation of mesoporous silica nanoparticles with different sizes and study on the correlation between size and toxicity / 药学学报

To investigate the crucial role of particle size in the biological effects of nanoparticles, a series of mesoporous silica nanoparticles (MSNs) were prepared with particle size gradients (50, 100, 150, 200 nm) with the traditional Stober method and adjusting the type and ratio of the silica source. The correlation between toxicity and size-caused biological effects were then further examined both in vitro and in vivo. The results indicated that the prepared MSNs had a uniform size, good dispersal, and ordered mesoporous structure. Hemolytic toxicity was found to be independent of particle size. At the cellular level, MSNs with smaller particle sizes were more readily internalized by cells, which initiated to more intense oxidative stress, therefor inducing higher cytotoxicity, and apoptosis rate. In vivo studies demonstrated that MSNs primarily accumulated in the liver and kidneys of mice. Pharmacokinetic analysis revealed that larger MSNs were eliminated more efficiently by the urinary system than smaller MSNs. The mice's body weight monitoring, blood tests, and pathological sections of major organs indicated good biocompatibility for MSNs of different sizes. Animal welfare and the animal experimental protocols were strictly consistent with related ethics regulations of Zhejiang Chinese Medical University. Overall, this study prepared MSNs with a particle size gradient to investigate the correlation between toxicity and particle size using macrophages and endothelial cells. The study also examined the biosafety of MSNs with different particle sizes in vivo and in vitro, which could help to improve the safety design strategy of MSNs for drug delivery systems.

Adapted physical education programs for psychomotor development in school settings for children with intellectual and developmental disabilities: a systematic review / 中国康复理论与实践

ObjectiveTo analyze the effect of physical activity in an adaptive physical education program on the psychomotor development of children with intellectual and developmental disabilities in the school setting. MethodsLiterature related to adaptive physical education programs and psychomotor development for children with intellectual and developmental disabilities were retrieved from EBSCO, PubMed, Embase, Web of Science and CNKI, from the establishment of the library to May, 2023, and systematically reviewed. ResultsSeven English literatures of randomized controlled trials were included, from four countries, involving 236 subjects, aged six to 18 years. The main sources were journals in the fields of sport and psychomotor, developmental disorders, adapted physical education, and children's psychomotor, with publication dates centered after 2016. Physical activity components of adaptive physical education programs in school settings primarily included muscle and balance training, perceptual-motor training, walking up and down stairs, aerobic exercise using equipment (e.g., treadmills, steppers, cross-trainers, and stationary bikes), sit-ups, jumping exercises, rhythmic activities, simultaneous static and dynamic balancing activities while focusing on visual inputs, changing positions at different rhythms and moving through space, breathing and stretching exercises, adapted table tennis motor skill training, ball control exercises, and hand-eye coordination exercises, with an intervention of light-moderate intensity, 45 to 60 minutes a time, one to five times a week, for eight to 24 weeks. The health benefit maily included the enhancement of rhythmic perception as well as the improvement of integrated visual, auditory, and tactile perception; improving muscular strength and endurance, total locomotor capacity and fine-motor capacity such as fine-motor integration, running speed and agility, and balance; improving physical flexibility and coordination, such as upper limb coordination, static balance, strength and flexibility; improvement of correct response, sustained response, and theoretical level of reactivity, and motor flexibility and agility; significant improvements in self-care (eating, dressing, and self-direction), increasing in the number of sit-ups to standard, increasing success in jumping for a ball, and improving motor skill proficiency and executive functioning. ConclusionThis systematic review constructed a PICO for the psychomotor development of children with intellectual and developmental disabilities participating in physical activity in the school setting with an adaptive physical education program based on the PRISMA guidelines. The adaptive physical education program may promote psychomotor development in children with intellectual and developmental disabilities in five main areas: perception, motor control, coordination, reaction time, and movement planning and execution.

Psychological and behavioral benefits of adapted yoga exercise for children with autism spectrum disorder in special education schools: a systematic review / 中国康复理论与实践

ObjectiveThe psychological and behavioral health benefits participating in yoga activities for children with autism spectrum disorder (ASD) in special education schools were reviewed using the theory and methodology of the International Classification of Functioning, Disability and Health (ICF). MethodsThe literature on benefits of yoga in psychological and behavioral health for students with ASD from special education schools participating in yoga activities was searched from PubMed, Embase, Web of Science and CNKI, from January, 2010 to July, 2023, and a systematic review was conducted. ResultsSeven papers from USA, India and Australia were included, mainly from the journals related to autism, sports therapy, and health psychology, published after 2018. The study design was all randomized controlled trials, featuring a total of 207 children with ASD aged five to 15 years. Adopted yoga interventions mainly included Mandala yoga postures, traditional yoga (breathing, posture, partner posture and relaxation) activities, etc. These simple yoga activities were incorporated into the physical health curriculum of special education schools. The benefits of yoga on psychological and behavioral health of students with ASD were mainly reflected in the following aspects: in the field of cognition, it significantly improved working memory, task monitoring, planning/organization and other aspects in reactive joint attention function and executive function; in the field of emotional development and control, it enhanced the ability of emotions/expressing emotions, empathy for others, and awareness of emotional control, and reduced in anxiety states, irritability that occurred in social, emotional, behavioral aspects, and hyperactivity and aggressive behavior; in the field of social and team activities, it improved speech/communication skills, social skills, and teamwork; in the field of psychomotor, it improved overall motor and imitation skills, exercise-related health behaviors, and sedentary behaviors. Yoga activities also relieved sleep problems. The frequency of intervention ranged from twelve to 60 minutes, one to six times a week for eight to 45 weeks. ConclusionIn the context of special education schools, the health benefits of adapted yoga activities are primarily reflected in improving the psychological health, motor function, and social skills of children with ASD.

Establishment and evaluation of in vitro galectin-3 inhibitor screening model / 药学学报

Galectin-3 (Gal-3) belongs to the galectin family and is specific in binding β-galactoside. Through its C-terminal domain, Gal-3 binds to the galactoside group of the glycosylated insulin receptor (IR) and inhibits IR signaling pathway, which leads to the insulin resistance. Thus, Gal-3 is a potential therapeutic target for the treatment of insulin resistance and type 2 diabetes. Here we report a simple Gal-3 screening model based on the property that Gal-3 binds to the galactoside. We expressed and purified human Gal-3 in Escherichia coli (E.coli), and labeled it with fluorescein isothiocyanate (FITC) in vitro. After incubating FITC labeled Gal-3 (Gal-3-FITC) with PANC-1 cells, which express glycosylated membrane protein, PANC-1 cells started to show green fluorescent signal due to the Gal-3-FITC binding to the glycosylated membrane protein. Gal-3 inhibitor disrupts the binding of Gal-3-FITC and PANC1 cells, subsequently leads to the decrease of the fluorescent signal in PANC-1 cells. We can evaluate the inhibitory efficiency of Gal-3 inhibitors through measurement of the fluorescent signal. Further studies show this model is simple, stable, and repeatable with a Z' factor between 0.7 and 0.85. In sum, we have successfully established an in vitro high-throughput screening model for Gal-3 inhibitors.

Study on the correlation between meibomian gland dysfunction and sleep quality / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To study the correlation between meibomian gland dysfunction(MGD)patients and their sleep quality.METHODS: Retrospective case-control study. A total of 150 MGD patients treated in our hospital from January 2021 to October 2022 were selected and divided into sleep disorder group(75 cases, PSQI>10 points)and control group(75 cases, PSQI≤10 points)according to the Pittsburgh sleep quality index(PSQI). Both groups were scored using the ocular surface disease index(OSDI), underwent meibomian gland-related examinations(eyelid margin morphology, meibomian gland secretion ability, meibomian gland secretion quality score), corneal fluorescein staining(FL)score, Schirmer Ⅰ test(SⅠt), tear film break-up time(BUT)was measured, and sleep indicators(sleep quality, sleep latency, subjective sleep quality, sleep time)were evaluated.RESULTS: There were significant differences in OSDI score, FL score, SⅠt, BUT, eyelid margin morphology score, meibomian gland secretion ability score, and meibomian gland secretion quality score between the two groups(P<0.05). In the sleep disorder group, PSQI score, sleep latency score, subjective sleep quality score, and sleep time score were significantly positively correlated with OSDI score, FL score, meibomian gland secretion ability score, and meibomian gland secretion quality score(P<0.05); PSQI score, subjective sleep quality score, and sleep time score were significantly positively correlated with eyelid margin morphology score(P<0.05); PSQI score, sleep latency score, and subjective sleep quality score were significantly negatively correlated with BUT and SⅠt(P<0.05); sleep time score was significantly negatively correlated with BUT(P<0.05); sleep latency score was not significantly correlated with eyelid margin morphology score(P>0.05); sleep time score was not significantly correlated with SⅠt(P>0.05).CONCLUSION:The ocular surface condition of MGD patients is correlated with multiple sleep quality indicators, and a decline in sleep quality may increase the risk of MGD.

Secular trends of age at menarche and age at menopause in women born since 1951 from a county of Shandong Province, China / 北京大学学报(医学版)

OBJECTIVE@#To describe the secular trends of age at menarche and age at natural menopause of women from a county of Shandong Province.@*METHODS@#Based on the data of the Premarital Medical Examination and the Cervical Cancer and Breast Cancer Screening of the county, the secular trends of age at menarche in women born in 1951 to 1998 and age at menopause in women born in 1951 to 1975 were studied. Joinpoint regression was used to identify potential inflection points regarding the trend of age at menarche. Average hazard ratios (AHR) of early menopause among women born in different generations were estimated by performing multivariate weighted Cox regression.@*RESULTS@#The average age at menarche was (16.43±1.89) years for women born in 1951 and (13.99±1.22) years for women born in 1998. The average age at menarche was lower for urban women than that for rural women, and the higher the education level, the lower the average age at menarche. Joinpoint regression analysis identified three inflection points: 1959, 1973 and 1993. The average age at menarche decreased annually by 0.03 (P < 0.001), 0.08 (P < 0.001), and 0.03 (P < 0.001) years respectively for women born during 1951-1959, 1960-1973, and 1974-1993, while it remained stable for those born during 1994-1998 (P=0.968). As for age at menopause, compared with women born during 1951-1960, those born during 1961-1965, 1966-1970 and 1971-1975 showed a gradual decrease in the risk of early menopause and a tendency to delay the age at menopause. The stratified analysis presented that the risk of early menopause gradually decreased and the age of menopause showed a significant delay among those with education level of junior high school and below, but this trend was not obvious among those with education level of senior high school and above, where the risk of early menopause decreased and then increased among those with education level of college and above, and the corresponding AHRs were 0.90 (0.66-1.22), 1.07 (0.79-1.44) and 1.14 (0.79-1.66).@*CONCLUSION@#The age at menarche for women born since 1951 gradually declined until 1994 and leveled off, with a decrease of nearly 2.5 years in these years. The age at menopause for women born between 1951 and 1975 was generally delayed over time, but the trend of first increase and then decrease was observed among those with relatively higher education levels. In the context of the increasing delay in age at marriage and childbearing and the decline of fertility, this study highlights the necessity of the assessment and monitoring of women' s basic reproductive health status, especially the risk of early menopause.

Factors associated with malnutrition in infants with congenital heart disease within one year after surgery / 中华儿科杂志

Objective: To explore the risk factors of malnutrition in infants with congenital heart disease within one year after surgery. Methods: This retrospective cohort study selected 502 infants with congenital heart disease who underwent surgical treatment in Guangzhou Women and Children's Medical Center from February 2018 to January 2019. Their basic information and clinical data were analyzed, and their nutrition status after the surgery was followed up by questionnaire survey. Weight-for-age Z score (WAZ)≤-2 one year after operation was defined as malnutrition group, and WAZ>-2 was non-malnutrition group. The perioperative indicators and complementary food advancement were compared between the two groups by chi-square test, t-test, and Kruskal-Wallis test. The risk factors of malnutrition were analyzed by Logistic regression. Results: A total of 502 infants were selected, including 301 males and 201 females, with the age of 4.1 (2.0, 6.8) months. There were 90 cases in malnutrition group and 412 cases in non-malnutrition group. The body length and weight at birth in the malnutrition group were lower than those in the non-malnutrition group ((47.8±3.8) vs. (49.3±2.5) cm, (2.7±0.6) vs.(3.0±0.5) kg, both P<0.001). The proportion of paternal high school education or above and the proportion of family per capita income of 5 000 yuan or above in the malnutrition group were lower than those in the non-malnutrition group ((18.9% (17/90) vs. 30.8% (127/412), 18.9% (17/90) vs. 33.7% (139/412), both P<0.05). Compared to the non-malnutrition group, the proportion of complex congenital heart disease in the malnutrition group was higher (62.2% (56/90) vs. 47.3% (195/412), P<0.05). The postoperative mechanical ventilation time, postoperative intensive care unit (ICU) stay time, postoperative hospital stay, total length of ICU stay and total hospital stay in the malnutrition group were significantly longer than those in non-malnutrition group (all P<0.05). The proportion of egg and fish supplementation over 2 times/week within one year after the surgery was also lower in the malnutrition group (both P<0.05). Logistic regression analysis showed that mother's weight at delivery (OR=0.95,95%CI 0.91-0.99), the pre-operative WAZ≤-2 (OR=6.04, 95%CI 3.13-11.65), the complexity of the cardiac disease (OR=2.23, 95%CI 1.22-4.06), the hospital stay after the surgery over 14 days (OR=2.61, 95%CI 1.30-5.26), the types of complementary food<4 (OR=2.57, 95%CI 1.39-4.76), and the frequency of meat and fish<2 times/week (OR=2.11, 95%CI 1.13-3.93) were the risk factors associated with malnutrition within one year after the surgery. Conclusion: Mother's weight at delivery pre-operative nutritional status, complexity of cardiac disease, postoperative hospital stay, types of daily supplements and frequency of fish are risk factors associated with malnutrition within one year after surgery in children with congenital heart disease.

Analysis of tuberculosis epidemiological characteristics and drug resistance among the floating population in Beijing in 2019 / 中华流行病学杂志

Objective: To analyze the epidemic characteristics and drug resistance of pulmonary tuberculosis among the floating population in Beijing and to provide a scientific basis for formulating strategies for the prevention and control of tuberculosis among the floating population. Methods: Data of tuberculosis patients who were positive for Mycobacterium tuberculosis culture was collected from 16 districts and one municipal institution of tuberculosis control and prevention in Beijing in 2019. The strain samples were tested for drug sensitivity by the proportional method. According to household registration location, patients were divided into the floating population and Beijing registration. SPSS 19.0 software analyzed tuberculosis patients' epidemic characteristics and drug resistance in the floating population. Results: In 2019, there were 1 171 culture-positive tuberculosis patients in Beijing, among the floating population, 593 (50.64%) patients were identified, with a male-to-female sex ratio of 2.2∶1 (409∶184). Compared to patients under household registration as Beijing residents, a higher proportion of young adults aged 20-39 years (65.09%,386/593) were noticed, with 55.65% (330/593) reported from the urban areas and 96.80% (574/593) were reported the first time. The differences were statistically significant (all P<0.05). After completing the drug sensitivity test, 37 cases were with multiple drug-resistant tuberculosis, accounting for 6.24% (37/593). The rates of isoniazid resistance (42.11%,8/19) and multidrug resistance (21.05%,4/19) in floating population patients after retreatment were significantly higher than those in newly treated patients (11.67%, 67/574 and 5.75%, 33/574), and the differences were statistically significant (all P<0.05). Conclusions: Most patients with tuberculosis in the floating population in Beijing in 2019 were young males aged 20-39 years. The reporting areas were urban areas and the newly treated patients mainly. The patients with tuberculosis in the re-treated floating population were more likely to suffer from multidrug and drug resistance, which should be taken as the key population for prevention and control.

Analysis of the characteristics of retracted scientific papers in the field of global liver diseases published by Chinese scholars / 中华肝脏病杂志

Objective: To analyze the characteristics of scientific papers in the field of global liver diseases published by Chinese scholars that were retracted for diverse reasons from the Retraction Watch database, so as to provide a reference to publishing-related papers. Methods: The Retraction Watch database was retrieved for retracted papers in the field of global liver disease published by Chinese scholars from March 1, 2008 to January 28, 2021. The regional distribution, source journals, reasons for retraction, publication and retraction times, and others were analyzed. Results: A total of 101 retracted papers that were distributed across 21 provinces/cities were retrieved. Zhejiang area (n = 17) had the most retracted papers, followed by Shanghai (n = 14), and Beijing (n = 11). The vast majority were research papers (n = 95). The journal PLoS One had the highest number of retracted papers. In terms of time distribution, 2019 (n = 36) had the most retracted papers. 23 papers, accounting for 8.3% of all retractions, were retracted owing to journal or publisher concerns. Liver cancer (34%), liver transplantation (16%), hepatitis (14%), and others were the main areas of retracted papers. Conclusion: Chinese scholars have a large number of retracted articles in the field of global liver diseases. A journal or publisher chooses to retract a manuscript after investigating and discovering more flawed problems, which, however, require further support, revision, and supervision from the editorial and academic circles.

Effective substances and mechanism of Yishen Guluo Mixture in treatment of chronic glomerulonephritis based on metabolomics and serum pharmacochemistry / 中国中药杂志

This study aimed to investigate the effective substances and mechanism of Yishen Guluo Mixture in the treatment of chronic glomerulonephritis(CGN) based on metabolomics and serum pharmacochemistry. The rat model of CGN was induced by cationic bovine serum albumin(C-BSA). After intragastric administration of Yishen Guluo Mixture, the biochemical indexes related to renal function(24-hour urinary protein, serum urea nitrogen, and creatinine) were determined, and the efficacy evaluations such as histopathological observation were carried out. The serum biomarkers of Yishen Guluo Mixture in the treatment of CGN were screened out by ultra-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry(UPLC-Q-TOF-MS) combined with multivariate statistical analysis, and the metabolic pathways were analyzed. According to the mass spectrum ion fragment information and metabolic pathway, the components absorbed into the blood(prototypes and metabolites) from Yishen Guluo Mixture were identified and analyzed by using PeakView 1.2 and MetabolitePilot 2.0.4. By integrating metabolomics and serum pharmacochemistry data, a mathematical model of correlation analysis between serum biomarkers and components absorbed into blood was constructed to screen out the potential effective substances of Yishen Guluo Mixture in the treatment of CGN. Yishen Guluo mixture significantly decreased the levels of 24-hour urinary protein, serum urea nitrogen, and creatinine in rats with CGN, and improved the pathological damage of the kidney tissue. Twenty serum biomarkers of Yishen Guluo Mixture in the treatment of CGN, such as arachidonic acid and lysophosphatidylcholine, were screened out, involving arachidonic acid metabolism, glycerol phosphatide metabolism, and other pathways. Based on the serum pharmacochemistry, 8 prototype components and 20 metabolites in the serum-containing Yishen Guluo Mixture were identified. According to the metabolomics and correlation analysis of serum pharmacochemistry, 12 compounds such as genistein absorbed into the blood from Yishen Guluo Mixture were selected as the potential effective substances for the treatment of CGN. Based on metabolomics and serum pharmacochemistry, the effective substances and mechanism of Yishen Guluo Mixture in the treatment of CGN are analyzed and explained in this study, which provides a new idea for the development of innovative traditional Chinese medicine for the treatment of CGN.

Clinical value of new coagulation biomarkers in pediatric sepsis / 中华儿科杂志

Objective: To evaluate the clinical value of new coagulation biomarkers including soluble thrombomodulin (sTM) and tissue plasminogen activator inhibitor complex (t-PAI·C) for the diagnosis and prognosis of sepsis in children. Methods: The prospective observational study enrolled 59 children who were diagnosed with sepsis including severe sepsis and septic shock in the Department of Pediatric Critical Care Medicine of Shanghai Children's Medical Center affiliated to the Medical College of Shanghai Jiao Tong University from June 2019 to June 2021. The sTM, t-PAI·C and conventional coagulation tests were detected on illness day one of sepsis. Twenty healthy children were selected as the control group, and the above parameters were detected on the day of inclusion. Children with sepsis were divided into survival group and non-survival group according to prognosis at discharge. Baseline comparisons between groups were performed using Mann-Whitney U test. Multivariate Logistic regression analysis was used to evaluate the risk factors for the diagnosis and prognosis of sepsis in children. Receiver operating characteristic (ROC) curve was conducted to evaluate the predictive values of above variables for the diagnosis and prognosis of sepsis in children. Results: The sepsis group included 59 patients (39 boys and 20 girls), aged 61(22, 136)months. There were 44 patients in the survival group and 15 patients in the non-survival group, respectively. The control group consisted of 20 boys, aged 107 (94,122) months. Patients in the sepsis group had higher sTM and t-PAI·C ((12 (9, 17)×103 vs. 9(8, 10)×103 TU/L, 10(6, 22) vs. 2 (1, 3) μg/L, Z=-2.15, -6.05, both P<0.05) compared with children in the control group. The t-PAI·C was superior to sTM for the diagnosis of sepsis. The areas under the curve (AUC) of t-PAI·C and sTM for the diagnosis of sepsis were 0.95 and 0.66, respectively, and the optimal cut-off value were 3 μg/L and 12×103 TU/L, respectively. Patients in the survival group had lower sTM (10 (8, 14)×103 vs. 17 (11, 36)×103 TU/L, Z=-2.73, P=0.006) than those in the non-survival group. Logistic regression analysis showed that sTM was a risk factor for death at discharge (OR=1.14, 95%CI 1.04-1.27, P=0.006). The AUC of sTM and t-PAI·C for predicting death at discharge were 0.74 and 0.62, respectively, and the optimal cut-off values were 13×103 TU/L and 6 μg/L, respectively. The AUC of sTM combined with platelet counts for predicting death at discharge was 0.89, which was superior to sTM and t-PAI·C. Conclusion: The sTM and t-PAI·C had clinical application values in diagnosing and predicting prognosis in pediatric sepsis.

Clinicopathological features of patients with RET fusion-positive non-small cell lung cancer / 中华病理学杂志

Objective: To investigate the clinicopathological features, treatment and prognosis of patients with RET fusion positive non-small cell lung cancer (NSCLC). Methods: A total of 1 089 NSCLCs were retrieved at Affiliated Hospital of Jiangnan University from August 2018 to April 2020. In all cases, multiple gene fusion detection kits (fluorescent PCR method) were used to detect the gene status of RET, EGFR, ALK, ROS1, KRAS, BRAF and HER2; and immunohistochemical method was used to detect the expression of PD-L1 and mismatch repair related proteins. The correlation between RET-fusion and patients' age, gender, smoking history, tumor stage, grade, pathologic type, and PD-L1, mismatch repair related protein expression was analyzed. Results: There were 22 cases (2.02%) detected with RET fusion-positive in 1 089 NSCLC patients, in which 11 males and 11 females; and the median age was 63.5 years. There were 20 adenocarcinomas, including 11 acinar predominant adenocarcinoma (APA), five solid predominant adenocarcinoma (SPA) and four lepidic predominant adenocarcinoma (LPA); There were one case each of squamous cell carcinoma (non-keratinizing type) and sarcomatoid carcinoma (pleomorphic carcinoma). There were 6 and 16 patients with RET fusion-positive who were in stage Ⅰ-Ⅱ and Ⅲ-Ⅳ respectively, and 16 cases with lymph node metastasis, 11 cases with distant metastasis. Among RET fusion-positive cases, one was detected with HER2 co-mutation. The tumor proportion score of PD-L1≥1% in patients with RET fusion positive lung cancer was 54.5% (12/22). Defects in mismatch repair protein expression were not found in patients with RET fusion positive NSCLC. Four patients with RET fusions positive (two cases of APA and two cases of SPA) received pratinib-targeted therapy, and two showed benefits from this targeted therapy. Conclusions: The histological subtypes of RET fusions positive NSCLC are more likely to be APA or SPA. RET fusion-positive NSCLC patients are associated with advanced clinical stage, lymph node metastases, and they may benefit from targeted therapy with RET-specific inhibitors.

Effect evaluation of various nanofiltration systems for filtering intravenous human immunoglobulin / 中国生物制品学杂志

@#Abstract： Objective To evaluate the filtration effects of various nanofiltration systems on intravenous human immunog⁃ lobulin（IVIG）in order to screen the optimal nanofiltration system. Methods Various nanofilters were used for IVIG filtration to determine the best one and then various prefilters were selected to combine with the optimal nanofilter for IVIG filtration to determine the optimal nanofiltration system. Results The tangential flow（cross flow）nanofilter showed better filtering effect than dead end（direct current）nanofilter，and nanofilter C was the best one. The effect of deep filtration prefilter was better than that of absolute filtration prefilter，and prefilter Y1 in series with nanofilter C was the optimal nanofiltration system. Conclusion The optimal nanofiltration system was determined through the effect evaluation of various nanofiltration systems filtering for IVIG.

Biphasic Cholinergic Modulation of Reverberatory Activity in Neuronal Networks / 神经科学通报·英文版

Acetylcholine (ACh) is an important neuromodulator in various cognitive functions. However, it is unclear how ACh influences neural circuit dynamics by altering cellular properties. Here, we investigated how ACh influences reverberatory activity in cultured neuronal networks. We found that ACh suppressed the occurrence of evoked reverberation at low to moderate doses, but to a much lesser extent at high doses. Moreover, high doses of ACh caused a longer duration of evoked reverberation, and a higher occurrence of spontaneous activity. With whole-cell recording from single neurons, we found that ACh inhibited excitatory postsynaptic currents (EPSCs) while elevating neuronal firing in a dose-dependent manner. Furthermore, all ACh-induced cellular and network changes were blocked by muscarinic, but not nicotinic receptor antagonists. With computational modeling, we found that simulated changes in EPSCs and the excitability of single cells mimicking the effects of ACh indeed modulated the evoked network reverberation similar to experimental observations. Thus, ACh modulates network dynamics in a biphasic fashion, probably by inhibiting excitatory synaptic transmission and facilitating neuronal excitability through muscarinic signaling pathways.

Target versus sub-target dose of renin-angiotensin system inhibitors on survival in elderly patients with heart failure with reduced ejection fraction: a systematic review and meta-analysis / 老年心脏病学杂志（英文版）

BACKGROUND@#The efficiency of the target versus sub-target dose of renin-angiotensin system inhibitors (RASIs) in elderly patients with heart failure (HF) with reduced ejection fraction (HErEF) remains unclear.@*METHODS@#PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched from database inception through March 2022 for randomized controlled trials (RCTs) and observational studies considering the effect of the target versus sub-target dose of RASIs on survival in elderly patients (≥ 60 years) with HErEF. The primary outcome was all-cause mortality. The secondary outcomes were cardiac mortality, HF hospitalization, and the composite endpoint of mortality or HF hospitalization. A meta-analysis was conducted to generate combined hazard ratio (HR) and 95% CI.@*RESULTS@#Seven studies (two RCTs and five observational studies) enrolling 16,634 patients were included. A pooled analysis suggested that the target versus sub-target dose of RASIs led to lower rates of all-cause mortality (HR = 0.92, 95% CI: 0.87-0.98, I2 = 21%) and cardiac mortality (HR = 0.93, 95% CI: 0.85-1.00, I2 = 15%) but not reduced rates of HF hospitalization (HR = 0.94, 95% CI: 0.88-1.01, I2 = 0) and the composite endpoint (HR = 1.03, 95% CI: 0.91-1.15, I2 = 51%). However, the target dose of RASIs was associated with a similar primary outcome (HR = 0.85, 95% CI: 0.64-1.14, I2 = 0) in a subgroup of very elderly patients > 75 years of age.@*CONCLUSIONS@#Our analysis suggests that the target dose of RASIs has a better survival benefit in elderly patients with HFrEF compared to the sub-target dose of RASIs. However, the sub-target dose of RASIs is associated with a similar mortality rate in very elderly patients > 75 years of age. Future high-quality and adequately powered RCTs are warranted.

Development and clinical application of a new reduction device for the treatment of tibial plateau fracture under arthroscopic monitoring / 中国骨伤

OBJECTIVE@#To develop a reduction device for the arthroscopy-assisted treatment of tibial plateau fracture and explore its clinical efficacy.@*METHODS@#From May 2018 to September 2019, 21 patients with tibial plateau fracture were treated, including 17 males and 4 females. Their ages ranged from 18 to 55 years old with an average of (38.6±8.7) years old. There were 5 cases of Schatzker typeⅡand 16 cases of Schatzker type Ⅲ. The self-designed reductor combined with arthroscope was used for auxiliary reduction and fixation(minimally invasive percutaneous plate osteosynthesis). The efficacy was analyzed by observing the operation time, blood loss, fracture healing time and knee function(HSS and IKDC scoring criteria).@*RESULTS@#All the 21 patients were followed up for 8 to 24 with an average of(14.0±3.1) months. The operative time ranged from 70 to 95 min with an average of(81.7±7.6)min, incision length ranged from 4 to 7 cm with an average of(5.3±0.9) cm, intraoperative blood loss ranged from 20 to 50 ml with an average of(35.3±5.2) ml, postoperative weight-bearing time ranged from 30 to 50 d with an average of(35.1±9.2) d, fracture healing time ranged from 65 to 90 d with an average of(75.0±4.4) d, and complications were 0 cases, respectively. The fracture was well healed and no screw plate fracture was observed. The knee function scores of HSS and IKDC 18 months after operation were significantly higher than those before operation(P<0.05).@*CONCLUSION@#The custom-made reduction tool for the arthroscopic management of tibial plateau fracture is reasonable in design and simple in operation. The specific reduction tool could effectively reduce the fracture, and shorten the fixation time with minimally invasive procedure.

Correlations between appearance traits and internal quality of Bupleurum scorzonerifolium roots based on theory of "quality evaluation through morphological identification" / 中国中药杂志

It is generally believed that high-quality Bupleurum scorzonerifolium roots possess specific morphological characteristics, being red, robust, and long with strong odor. However, the scientific connotation of these characteristics has not been elucidated. According to the theory of "quality evaluation through morphological identification", we studied the correlations between appearance traits(the RGB value of root surface, root length, root diameter, dry weight, and ratio of phloem to xylem) and content of main chemical components(volatile oils, total saponins, total flavonoids, total polysaccharides, and seven saikosaponins) of B. scorzonerifolium roots. Epson Scanner and ImageJ were used to scan the root samples and measure the appearance traits. Ultraviolet spectrophotometry and HPLC were employed to determine the content of chemical components. The correlation, regression, and cluster analyses were performed to study the correlations between the appearance traits and the content of chemical components. The results showed that the content of volatile oils and saikosaponins were significantly correlated with RGB value, root length, and root diameter, indicating that within a certain range, the roots being redder, longer, and thicker had higher content of volatile oils and saikosaponins. According to the appearance traits and chemical component content, the 14 samples from different producing areas were classified into four grades, and the differences in morphological traits and chemical component content were consistent among different grades. The findings in this study demonstrate that appearance traits(RGB value, root length, and root diameter) can be used to evaluate the quality of B. scorzonerifolium roots. Meanwhile, this study lays a foundation for establishing an objective quality evaluation method for B. scorzonerifolium roots.

Construction of an adenovirus vector expressing engineered splicing factor for regulating alternative splicing of YAP1 in neonatal rat cardiomyocytes / 南方医科大学学报

OBJECTIVE@#To construct an adenovirus vector expressing artificial splicing factor capable of regulating alternative splicing of Yap1 in cardiomyocytes.@*METHODS@#The splicing factors with different sequences were constructed against Exon6 of YAP1 based on the sequence specificity of Pumilio1. The PCR fragment of the artificially synthesized PUF-SR or wild-type PUFSR was cloned into pAd-Track plasmid, and the recombinant plasmids were transformed into E. coli DH5α for plasmid amplification. The amplified plasmids were digested with Pac I and transfected into 293A cells for packaging to obtain the adenovirus vectors. Cultured neonatal rat cardiomyocytes were transfected with the adenoviral vectors, and alternative splicing of YAP1 was detected using quantitative and semi-quantitative PCR; Western blotting was performed to detect the signal of the fusion protein Flag.@*RESULTS@#The transfection efficiency of the adenovirus vectors was close to 100% in rat cardiomyocytes, and no fluorescent protein was detected in the cells with plasmid transfection. The results of Western blotting showed that both the negative control and Flag-SR-NLS-PUF targeting the YAPExon6XULIE sequence were capable of detecting the expression of the protein fused to Flag. The results of reverse transcription-PCR and PCR demonstrated that the artificial splicing factor constructed based on the 4th target sequence of YAP1 effectively regulated the splicing of YAP1 Exon6 in the cardiomyocytes (P < 0.05).@*CONCLUSION@#We successfully constructed adenovirus vectors capable of regulating YAP1 alternative splicing rat cardiomyocytes.

Investigation on the growth factor regulatory network of dermal fibroblasts in mouse full-thickness skin defect wounds based on single-cell RNA sequencing / 中华烧伤杂志

Objective: To explore the heterogeneity and growth factor regulatory network of dermal fibroblasts (dFbs) in mouse full-thickness skin defect wounds based on single-cell RNA sequencing. Methods: The experimental research methods were adopted. The normal skin tissue from 5 healthy 8-week-old male C57BL/6 mice (the same mouse age, sex, and strain below) was harvested, and the wound tissue of another 5 mice with full-thickness skin defect on the back was harvested on post injury day (PID) 7. The cell suspension was obtained by digesting the tissue with collagenase D and DNase Ⅰ, sequencing library was constructed using 10x Genomics platform, and single-cell RNA sequencing was performed by Illumina Novaseq6000 sequencer. The gene expression matrices of cells in the two kinds of tissue were obtained by analysis of Seurat 3.0 program of software R4.1.1, and two-dimensional tSNE plots classified by cell group, cell source, and gene labeling of major cells in skin were used for visual display. According to the existing literature and the CellMarker database searching, the expression of marker genes in the gene expression matrices of cells in the two kinds of tissue was analyzed, and each cell group was numbered and defined. The gene expression matrices and cell clustering information were introduced into CellChat 1.1.3 program of software R4.1.1 to analyze the intercellular communication in the two kinds of tissue and the intercellular communication involving vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and fibroblast growth factor (FGF) signal pathways in the wound tissue, the relative contribution of each pair of FGF subtypes and FGF receptor (FGFR) subtypes (hereinafter referred to as FGF ligand receptor pairs) to FGF signal network in the two kinds of tissue, and the intercellular communication in the signal pathway of FGF ligand receptor pairs with the top 2 relative contributions in the two kinds of tissue. The normal skin tissue from one healthy mouse was harvested, and the wound tissue of one mouse with full-thickness skin defect on the back was harvested on PID 7. The multiple immunofluorescence staining was performed to detect the expression and distribution of FGF7 protein and its co-localized expression with dipeptidyl peptidase 4 (DPP4), stem cell antigen 1 (SCA1), smooth muscle actin (SMA), and PDGF receptor α (PDGFRα) protein. Results: Both the normal skin tissue of healthy mice and the wound tissue of full-thickness skin defected mice on PID 7 contained 25 cell groups, but the numbers of cells in each cell group between the two kinds of tissue were different. Genes PDGFRα, platelet endothelial cell adhesion molecule 1, lymphatic endothelial hyaluronic acid receptor 1, receptor protein tyrosine phosphatase C, keratin 10, and keratin 79 all had distinct distributions on two-dimensional tSNE plots, indicating specific cell groups respectively. The 25 cell groups were numbered by C0-C24 and divided into 9 dFb subgroups and 16 non-dFb groups. dFb subgroups included C0 as interstitial progenitor cells, C5 as adipose precursor cells, and C13 as contractile muscle cells related fibroblasts, etc. Non-dFb group included C3 as neutrophils, C8 as T cells, and C18 as erythrocytes, etc. Compared with that of the normal skin tissue of healthy mice, the intercellular communication in the wound tissue of full-thickness skin defected mice on PID 7 was more and denser, and the top 3 cell groups in intercellular communication intensity were dFb subgroups C0, C1, and C2, of which all communicated with other cell groups in the wound tissue. In the wound tissue of full-thickness skin defected mice on PID 7, VEGF signals were mainly sent by the dFb subgroup C0 and received by vascular related cell groups C19 and C21, PDGF signals were mainly sent by peripheral cells C14 and received by multiple dFb subgroups, EGF signals were mainly sent by keratinocyte subgroups C9 and C11 and received by the dFb subgroup C0, and the main sender and receiver of FGF signals were the dFb subgroup C6. In the relative contribution rank of FGF ligand receptor pairs to FGF signal network in the normal skin tissue of healthy mice and the wound tissue of full-thickness skin defected mice on PID 7, FGF7-FGFR1 was the top 1, and FGF7-FGFR2 or FGF10-FGFR1 was in the second place, respectively; compared with those in the normal skin tissue, there was more intercellular communication in FGF7-FGFR1 signal pathway, while the intercellular communication in FGF7-FGFR2 and FGF10-FGFR1 signal pathways decreased slightly or did not change significantly in the wound tissue; the intercellular communication in FGF7-FGFR1 signal pathway in the wound tissue was stronger than that in FGF7-FGFR2 or FGF10-FGFR1 signal pathway; in the two kinds of tissue, FGF7 signal was mainly sent by dFb subgroups C0, C1, and C2, and received by dFb subgroups C6 and C7. Compared with that in the normal skin tissue of healthy mouse, the expression of FGF7 protein was higher in the wound tissue of full-thickness skin defected mouse on PID 7; in the normal skin tissue, FGF7 protein was mainly expressed in the skin interstitium and also expressed in the white adipose tissue near the dermis layer; in the two kinds of tissue, FGF7 protein was co-localized with DPP4 and SCA1 proteins and expressed in the skin interstitium, co-localized with PDGFRα protein and expressed in dFbs, but was not co-localized with SMA protein, with more co-localized expression of FGF7 in the wound tissue than that in the normal skin tissue. Conclusions: In the process of wound healing of mouse full-thickness skin defect wound, dFbs are highly heterogeneous, act as potential major secretory or receiving cell populations of a variety of growth factors, and have a close and complex relationship with the growth factor signal pathways. FGF7-FGFR1 signal pathway is the main FGF signal pathway in the process of wound healing, which targets and regulates multiple dFb subgroups.

Influence of continuous light and benzene exposure on erythrocyte parameters and expression of miRNA-144/451 in mice / 中国职业医学

@#Abstract: Objective To explore the effects of continuous light and benzene exposure on peripheral blood erythrocyte - Methods parameters and expression of miR 144/451 in the bone marrow of mice. This was a 2×2 factorial design. Photoperiod ， ， factor was set as normal and continuous light levels and mice were treated for 12 hours/12 hours light/dark or 24 hours light - respectively. The benzene exposure factor was set as non exposure and exposure levels. Mice were exposed to benzene by static 3 ， inhalation with a mass concentration of 0.0 and 32.5 mg/m for three hours per day five days per week for a total of four weeks. ， ， Specific pathogen free male C57BL/6 J mice were randomly divided into negative control group simple continuous light group - - ， ， simple benzene exposure group and combined exposure group with 12 mice per group. After benzene exposure peripheral ， blood was collected for the detection of erythrocyte parameters in four periods. After the mice were sacrificed the expression of - - - - miR 451a and miR 144 5p was detected by real time fluorescence quantitative polymerase chain reaction in bone marrow Results （ ）， ， tissues. The hematocrit volume HCT mean corpuscular volume mean corpuscular hemoglobin concentration （ ） - MCHC and mean corpuscular hemoglobin in peripheral blood and the relative expression of miR 451a in bone marrow tissue （ P< ） ， were statistically significant only in mice with benzene exposure all 0.05 . Among them the MCHC of benzene exposed （P< ）， （ P< ） - mice increased 0.05 but the other four indexes decreased all 0.05 compared with non benzene exposed mice. In thenegative control group the change of red blood cells count hemoglobin level and HCT in peripheral blood were rhythmical all P < ） ， （ P > ） rhythmical 0.05 . However the indexes above were out of rhythm all rhythmical 0.05 in the simple continuous light group and the - （ P > combined exposure group. The change of hemoglobin level and HCT of peripheral blood were also out of rhythm all rhythmical ） - - 0.05 in the simple benzene exposure group. The relative expression of miR 451a in bone marrow tissues of negative control （ P < ）， - group and simple continuous light group was rhythmical all rhythmical 0.05 while the relative expression of miR 451a in simple - - （ P > ）Conclusion benzene exposure group and combined exposure group was out of rhythm all rhythmical 0.05 . Benzene exposure ， induced changes in erythrocyte parameters of mice are independent effect and its mechanism may be related to the rhythmic - ， expression disorder of miR 451a in bone marrow tissues. Continuous light exposure benzene exposure and their interactions can ， interfere with the circadian rhythm of erythrocyte parameters such as red blood cell count hemoglobin and HCT to some extent.