BACKGROUND:As a member of bone morphogenetic proteins,growth differentiation factor-5 shows promising potential in the application of cartilage and bone repair.The affinity of growth differentiation factor-5 onto bone tissue determines protein use efficiency,so it is of great significance to prepare growth differentiation factor-5 with bone targeting capability. OBJECTIVE:To modify growth differentiation factor-5 using bisphosphonates and investigate the effects of modified protein on the growth of preosteoblasts in mice. METHODS:Pamidronate disodium/growth differentiation factor-5 complex was prepared using chemical crosslinking to couple growth differentiation factor-5 with pamidronate disodium.The functional groups and structures of the complex were characterized using Fourier transform infrared spectroscopy and circular dichromatography.To determine the bone targeting in vitro,the binding of the modified growth differentiation factor-5 with calcium phosphate and in vitro release amount of growth differentiation factor-5 were measured with an ELISA kit.Growth differentiation factor-5(control group)and the pamidronate disodium/growth differentiation factor-5 complex(experimental group)were co-cultured with preosteoblasts MC3T3-E1.Individually cultured cells were blank controls.The effect of the complex on cell proliferation and differentiation was evaluated. RESULTS AND CONCLUSION:(1)The infrared spectroscopy and circular dichromatography results indicated that the bisphosphonate/growth differentiation factor-5 complex was successfully prepared without significant changes in the protein secondary structure.In vitro protein adsorption results showed that growth differentiation factor-5 adsorption on calcium phosphate was increased by about one time after coupling with a bisphosphonate.In the presence of cysteine,growth differentiation factor-5 could be released from the bisphosphonate/growth differentiation factor-5 complex.(2)CCK-8 assay results showed that the absorbance value of the experimental group cultured for 4 and 7 days was higher than that of the control group and blank control group(P<0.000 1).After 7 days of culture,the expression of alkaline phosphatase in the experimental group was significantly higher than that in the control group and blank control group(P<0.000 1).After 13 days of culture,the content of calcium nodules in the experimental group was significantly higher than that in the control group and the blank control group(P<0.000 1).The results of qRT-PCR showed that the mRNA expression of alkaline phosphatase,osteocalcin and Runx2 in the experimental group was higher than that in the control group and the blank control group after 7 days of culture(P<0.01,P<0.001,P<0.000 1).(3)These findings exhibit that bisphosphonate modification can enhance the binding capacity of growth differentiation factor-5 to calcium phosphate as well as improve its biological activity.

Sleep deprivation refers to the loss of sleep caused by self-inflicted or external factors. There is increasing evidence that pregnancy is prone to sleep deprivation, which not only disrupts maternal functions but also affects offspring′s cognitive function. This article reviews the effects of sleep deprivation during pregnancy on offspring cognition and its underlying mechanisms, in order to establish a foundation for developing scientifically sound sleep strategies during pregnancy and to provide clinical insights for improving the neurodevelopment and cognitive function of offspring.

Objective:To observe the effects of ointment and massage on inflammation, oxidative stress and angiogenesis after skeletal muscle trauma, and to explore their mechanisms.Methods:Forty-two adult male Sprague-Dawley rats were randomly divided into a blank group ( n=6), an ointment and massage (O&M) group ( n=18) and a model group ( n=18). The blunt contusion model of gastrocnemius malformation was established in both the O&M and model groups using self-made percussion instruments. Two hours after successful modeling, the anti-inflammatory pain-relieving cream was applied to the injured area, and massaged evenly and gently for 5 minutes. That was repeated with an interval of 12 hours. No treatment was given to the model and blank groups. On the 1st, 3rd and 7th days after modeling, injured gastrocnemius muscles were resected after collecting abdominal blood. Hematoxylin-eosin (HE) staining and immunofluorescent (CD34) staining were applied, and serum superoxide dismutase (SOD) and malondialdehyde (MDA) contents were detected. Results:HE staining showed that at each time point the gastrocnemius muscle fibers of the model group were significantly more swollen and deformed, collapsed and dissolved than those of the blank group, with a large number of inflamed cells. The O&M group had better recovery, with more newly-generated muscle cells, less inflammatory infiltration and more normal cell shapes than the model group. Fluorescence was stronger in the O&M and model groups than in the blank group at each time point, with that of the O&M group significantly stronger than in the model group. The average SOD and MDA levels in the model and O&M groups were significantly higher than in the blank group, and on the 1st and 3rd days the O&M group′s average SOD level was significantly higher than the model group′s average, though by the 7th day there was no significant difference. The average MDA content of the O&M group was significantly lower than the model group′s average at each time point.Conclusion:Ointment and massage can effectively reduce the local inflammatory response and oxidative stress after a skeletal muscle injury. They can accelerate local angiogenesis, promoting the repair of damaged tissues.

Objective:To evaluate the clinical efficacy and safety of secukinumab in the treatment of moderate to severe the adults with plaque psoriasis.Methods:The clinical data from 183 adult patients with moderate to severe plaque psoriasis treated with secukinumab were collected.The patients received subcutaneous injections of secukinumab once a week at weeks 0,1,2,3,and 4,followed by an injection every 4 weeks,with each dose of 300 mg.The follow-up period was 52 weeks.The psoriasis area and severity index(PASI),body surface area(BSA),investigator global assessment(IGA),and dermatology life quality index(DLQI)scores of the patients with psoriasis were caculated.The clinical efficacy and safety of secukinumab in the treatment of moderate to severe plaque psoriasis were evaluated,and the influencing factors were analyzed.Results:Compared with week 0,the PASI、BSA、IGA and DLQI scores of the patients were significantly decreased at weeks 4,12,24,and 52 of secukinumab treatment(P<0.05).After treated with secukinumab,the percentages of the patients achieving PASI 75,PASI 90,and PASI 100 at week 4 were 95.6%,84.2%,and 47.5%,respectively;at week 12,they were 97.3%,95.6%,and 78.7%,respectively;at week 24,they were 97.8%,96.7%,and 84.2%,respectively;and at week 52,they were 98.4%,97.8%,and 83.6%,respectively.The percentages of the patients with BSA≤1%at weeks 4,12,24,and 52 were 80.9%,94.5%,95.6%,and 94.0%,respectively.The percentages of the patients with IGA score of 0/1 at week 4,12,24,and 52 were 86.3%,97.3%,96.7%,and 95.6%,respectively.The percentages of the patients with DLQI score of 0/1 at weeks 4,12,24,and 52 were 76.6%,89.1%,92.9%,and 91.8%,respectively.At week 4 of secukinumab treatment,there were significant differences in age,body mass index(BMI),disease duration,baseline PASI score,and history of previous biologic treatment between the patients in two groups(P<0.05).At week 24 of secukinumab treatment,there were significant differences in age and BMI between the patients in two groups(P<0.05).At week 4,BMI≥25 kg·m-2,disease duration≥10 years,baseline PASI score≥10,and a history of previous biologic treatment were risk factors affecting the recovery of the patient(P<0.05).At week 24,age≥40 years was a risk factor affecting the recovery of the patient(P<0.05).During the treatment period,44 out of 183 psoriasis patients reported 49 adverse reactions,and the adverse reaction rate was 24.0%.No serious adverse events or fatal adverse reactions occurred.The adverse reactions included upper respiratory tract infections in 23 cases,eczema-like skin lesions in 10 cases,skin fungal infections in 6 cases,urticaria in 3 cases,mild liver function abnormalities in 2 cases,folliculitis in 2 cases,conjunctivitis in 2 cases,and otitis media in 1 case.Conclusion:Secukinumab treatment for the adult patients with moderate to severe plaque psoriasis is rapid-acting and has lasting efficacy.The BMI,disease duration,baseline PASI score,history of previous biologic treatment,and age are the factors influencing the clinical efficacy of secukinumab.The overall safety is good,and secukinumab may be used as a first-line treatment option for moderate to severe plaque psoriasis.

Formative assessment emphasizes timely feedback to guide and improve the learning process, benefiting both students and teachers through the evaluation–feedback–improvement–reevaluation mechanism. The Pediatric College of Chongqing Medical University has widely applied formative assessment to standardized residency training, and at the same time, has actively researched this method in undergraduate education to employ various formative assessment tools to establish a formative assessment-based pediatric education model that has specialized characteristics and can be popularized. We have demonstrated that the formative assessment-based education model can improve the teaching quality of pediatric medical education, and better meet the requirements of higher education and the new situation of medical education in the age of new medicine.

The Omicron family of SARS-CoV-2 variants are currently driving the COVID-19 pandemic. Here we analyzed the clinical laboratory test results of 9911 Omicron BA.2.2 sublineages-infected symptomatic patients without earlier infection histories during a SARS-CoV-2 outbreak in Shanghai in spring 2022. Compared to an earlier patient cohort infected by SARS-CoV-2 prototype strains in 2020, BA.2.2 infection led to distinct fluctuations of pathophysiological markers in the peripheral blood. In particular, severe/critical cases of COVID-19 post BA.2.2 infection were associated with less pro-inflammatory macrophage activation and stronger interferon alpha response in the bronchoalveolar microenvironment. Importantly, the abnormal biomarkers were significantly subdued in individuals who had been immunized by 2 or 3 doses of SARS-CoV-2 prototype-inactivated vaccines, supporting the estimation of an overall 96.02% of protection rate against severe/critical disease in the 4854 cases in our BA.2.2 patient cohort with traceable vaccination records. Furthermore, even though age was a critical risk factor of the severity of COVID-19 post BA.2.2 infection, vaccination-elicited protection against severe/critical COVID-19 reached 90.15% in patients aged ≽ 60 years old. Together, our study delineates the pathophysiological features of Omicron BA.2.2 sublineages and demonstrates significant protection conferred by prior prototype-based inactivated vaccines.
Humans ; Aged ; Middle Aged ; COVID-19/prevention & control* ; SARS-CoV-2 ; Pandemics/prevention & control* ; China/epidemiology* ; Disease Outbreaks/prevention & control* ; Vaccination

Emerging evidence indicates that the gut microbiome contributes to the host immune response to infectious diseases. Here, to explore the role of the gut microbiome in the host immune responses in COVID-19, we conducted shotgun metagenomic sequencing and immune profiling of 14 severe/critical and 24 mild/moderate COVID-19 cases as well as 31 healthy control samples. We found that the diversity of the gut microbiome was reduced in severe/critical COVID-19 cases compared to mild/moderate ones. We identified the abundance of some gut microbes altered post-SARS-CoV-2 infection and related to disease severity, such as Enterococcus faecium, Coprococcus comes, Roseburia intestinalis, Akkermansia muciniphila, Bacteroides cellulosilyticus and Blautia obeum. We further analyzed the correlation between the abundance of gut microbes and host responses, and obtained a correlation map between clinical features of COVID-19 and 16 severity-related gut microbe, including Coprococcus comes that was positively correlated with CD3⁺/CD4⁺/CD8⁺ lymphocyte counts. In addition, an integrative analysis of gut microbiome and the transcriptome of peripheral blood mononuclear cells (PBMCs) showed that genes related to viral transcription and apoptosis were up-regulated in Coprococcus comes low samples. Moreover, a number of metabolic pathways in gut microbes were also found to be differentially enriched in severe/critical or mild/moderate COVID-19 cases, including the superpathways of polyamine biosynthesis II and sulfur oxidation that were suppressed in severe/critical COVID-19. Together, our study highlighted a potential regulatory role of severity related gut microbes in the immune response of host.
COVID-19 ; Clostridiales ; Gastrointestinal Microbiome ; Humans ; Immunity ; Leukocytes, Mononuclear ; SARS-CoV-2

Objective:To analyze the feasibility of developing clinical pediatrics curriculum for pediatric students at the pre-clinical stage, and to provide a basis for the subsequent curriculum construction.Methods:A total of 90 pediatric medical students were enrolled, including pre-clinical group (G1, third semester of the second year, n=47) and the clinical clerkship group (G2, seventh semester of the fourth year, n=43). A questionnaire survey was conducted to compare the two groups from three aspects: clinical interest, learning methods and learning ability. And 24 and 20 students were randomly selected from the two groups to participate a clinical course respectively. Both of the formative evaluation and in-class test were carried out to compare the learning performance and learning effect between G1 and G2. SPSS 22.0 was used for data analysis. The counting data were described by case number and rate, and the frequency between groups was compared by chi-square test. When the chi-square test condition is not met, Fisher's exact test was performed. Normal distribution test was carried out for measurement data. Two independent sample t test was conducted for the comparison between groups of normal distribution data and Mann-Whitney U test for the comparison between groups of skewed distribution respectively. Results:There was no significant difference in clinical interest and pre-clinical interest between the two groups (Fisher's exact probability method, P=0.252, 1.000). There were partial differences in learning methods: G1 spent more time learning after class ( Z=-2.36, P=0.018), learned more in spare time ( Z=2.53, P=0.011), learned more on the homework ( P=0.020), and had a higher preview rate ( Z=-5.07, P < 0.001). There were also partial differences in learning ability: G2 had better literature retrieval ability ( χ2=10.57, P=0.001); G2 had higher scores on class and extended class performance ( t=-3.18, P=0.004; t=-10.14, P<0.001). In terms of learning effect, G2 scored higher scores on only one multiple choice question ( t=-2.46, P=0.022). Conclusion:The pediatrics students at the pre-clinical stage have certain interest and ability to receive clinical pediatrics courses. Sufficient pre-class preparation and appropriate curriculum design are helpful to the early cultivation of student's clinical thinking.

Objective To evaluate the rupture risk of carotid atherosclerotic plaque under cervical rotatory manipulation. Methods The fluid-structure interaction (FSI) model of carotid atherosclerotic plaque was established, and tensile deformation of the plaque and lumen under cervical rotatory manipulation was simulated.Mechanical parameters such as the maximum flow shear stress(FSS), the maximum wall shear stress (WSS), the maximum plaque wall stress (PWS), wall tensile stress (WTS) and wall pressure (WP) of the plaque and lumen were recorded. Results Under 16% carotid tensile deformation, the maximum WSS of the plaque was 40.54 Pa. The maximum PWS was 66.16 kPa, which was far smaller than the threshold of plaque rupture.The maximum WTS of fiber cap and the maximum strain were 156.75 kPa and 0.56, which were larger than the fracture strain range. The maximum WTS of the lumen was 1 040.30 kPa, which approached the threshold of medial membrane rupture and might cause vascular injury. Conclusions When the cervical spine rotates to the end range of motion, large carotid artery stretch may cause damage to epidermal tissues of the plaque, leading to abscission. Lesions, ulcers, bleeding and vascular damage may form inside the plaque, which will affect stability of the plaque. Cervical rotatory manipulation should be performed cautiously in patients with cervical diseases who also have carotid atherosclerotic plaques.The finite element assessment of plaques before manipulation may be an effective safety screening method.

Objective:To analyze the effect of SBAR (situation, background, assessment, and recommendation) sign-out template in the standardized residency training in a neonatal ward.Methods:Based on SBAR communication mode, we designed and optimized neonatal ward sign-out checklist, and a total of 67 residents were trained for 2 weeks from April 2019 to June 2019, with control group (before training) and observation group (after training). The assessment indicators of sign-out information included sign-out duration, the incidence of sign-out errors, quality assessment scores and shift satisfaction (including sign-out satisfaction and self-evaluation) as well as competencies. A total of 1 553 children's morning shift data were collected, and SPSS 22. 0 was used for t test and chi-square test. Results:In the control group, the sign-out duration was (23.4±4.7) min, the incidence of sign-out errors was (43.6±6.6)%, quality assessment scores were (6.3±0.7) points, the satisfaction degree was (76.5±4.6)%, and the self-evaluation scores were (5.2±2.1) points. While, in the observation group, the sign-out duration was (15.9±3.2) min, the incidence of sign-out errors was (21.1±2.3)%, quality assessment scores were (8.9±0.9) points, the satisfaction degree was (94.1±2.9)%, and the self-evaluation scores were (8.9±0.8) points, with statistically significant difference ( P<0.05). There were statistically significant differences between the two groups in clinical skills and medical service ability [(2.2±0.1) vs. (3.8±0.3)], interpersonal communication ability [(2.6±0.5) vs. (4.2±0.1) points], teamwork ability [(3.1±0.2) vs. (4.6±0.3)], information and management ability [(2.5±0.5) vs. (4.2±0.2)] ( P<0.05). Conclusion:The SBAR template can improve sign-out process and the clinical skills of standardized training residents.