Screening of key genes in the pathogenesis of muscle atrophy in CKD-PEW children based on RNA sequencing.

BACKGROUND: In children with CKD, Protein Energy Wasting (PEW) is common, which affects the outcome of children and is an important cause of poor prognosis. We are aiming to explore the pathogenesis of muscle wasting in CKD-PEW children. METHODS: Blood samples of 32 children diagnosed with chronic kidney disease (CKD) and protein energy wasting (PEW) in our hospital from January 2016 to June 2021 were collected. RNA sequencing and bioinformatics analysis were performed. RESULTS: Based on GO (Gene Ontology) functional enrichment analysis, KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis and differential gene expression analysis, a total of 25 CKD-PEW related genes were obtained including CRP, IL6, TNF, IL1B, CXCL8, IL12B, IL12A, IL18, IL1A, IL4, IL10, TGFB2, TGFB1, TGFB3, ADIPOQ, NAMPT, RETN, RETNLB, LEP, CD163, ICAM1, VCAM1, SELE, NF-κB1, NF-κB2. The most significantly differentially expressed gene was NF-κB2 (adjusted P = 2.81 × 10-16), and its expression was up-regulated by 3.92 times (corresponding log2FoldChange value was 1.979). Followed by RETN (adjusted P = 1.63 × 10-7), and its expression was up-regulated by 8.306 times (corresponding log2FoldChange value was 2.882). SELE gene were secondly significant (adjusted P = 5.81 × 10-7), and its expression was down-regulated by 22.05 times (corresponding log2FoldChange value was -4.696). CONCLUSIONS: A variety of inflammatory factors are involved in the pathogenesis of CKD-PEW in children, and chronic inflammation may lead to the development of muscle atrophy in CKD-PEW. It is suggested for the first time that NF-κB is a key gene in the pathogenesis of muscle wasting in CKD-PEW children, and its increased expression may play an important role in the pathogenesis of muscle wasting in children with CKD-PEW.

Analysis on the household secondary attack rates of the SARS-CoV-2 Delta variant and the associated factors / 中华预防医学杂志

Objective: To evaluate the household secondary attack rates of the SARS-CoV-2 Delta variant and the associated factors. Methods: A COVID-19 outbreak caused by the Delta variant occurred in Nanjing in July 2021. A total of 235 cases with current addresses in Nanjing were reported from 171 households. The subjects in this study were selected from household close contact(s) of infected cases. The information on household index cases and their contacts were collected, and the household secondary attack rate (HSAR) and the risk factors were analyzed by the multi-factor logistic regression model. Results: A total of 234 cases of household close contacts and 64 household secondary cases were reported from 103 households, and the HSAR was 27.4% (64/234, 95%CI:22.0% to 33.4%). The proportions of household size for 2 to 3, 4 to 5, and 6 to 9 were 64.1% (66), 26.2% (27) and 9.7% (10), respectively. A total of 35 cases of household cluster outbreaks were reported (35/103, 34.0%). The number of the first case in the household (FCH) was 103 and males accounted for 27.2% (28 cases), with the median age (Q1, Q3) of 49 (9, 56). The number of household close contacts was 234 and males accounted for 59.0% (138 cases), with the median age (Q1, Q3) of 42 (20, 55) and the median exposure period (Q1, Q3) of 3 (1, 3) days. The multi-factor logistic regression model showed that the higher HSAR was observed in the FCH with the features of airport staff (OR=2.913, 95%CI:1.469-5.774), detection from home quarantine screening (OR=6.795, 95%CI:1.761-26.219) and detection from mass screening (OR=4.239, 95%CI:1.098-16.368). Meanwhile, higher HSAR was observed in cases with longer household exposure (OR=1.221, 95%CI:1.040-1.432), non-vaccination (OR=2.963, 95%CI:1.288-6.813) and incomplete vaccinations (OR=2.842, 95%CI:0.925-8.731). Conclusion: The generation interval of the Delta variant is shortened, and the ability of transmission within the household is enhanced. In the outbreak in Nanjing, the associated factors of HSAR are occupation, detection route, vaccination and exposure period.

Effect of out-hospital blood pressure management on prognosis of patients with acute aortic syndrome complicated with hypertension after TEVAR / 中华心血管病杂志

Objective: To investigate the influence of blood pressure control after discharge on prognosis of patients with acute aortic syndrome (AAS) complicated with hypertension who underwent thoracic endovascular aortic repair (TEVAR). Methods: This is a retrospective case analysis. Patients diagnosed with AAS complicated with hypertension and undergoing TEVAR in Northern Theater Command General Hospital from June 2002 to December 2021 were consecutively enrolled. Average systolic blood pressure (SBP) and the occurrence of endpoint events were recorded at one month, one year and every 2 years after TEVAR. According to the patients' average SBP, patients with average SBP<140 mmHg (1 mmHg=0.133 kPa) or<150 mmHg were divided into the target blood pressure achievement group, and the others were divided into target blood pressure non-achievement group. Endpoint events included all-cause death, aortic death, stroke, renal insufficiency, aortic related adverse events and a composite of these events (overall clinical adverse events), and re-accepting TEVAR. The incidence of endpoint events was compared between the two groups at each follow-up period. Results: A total of 987 patients were included, aged (55.7±11.7) years, including 779 male (78.9%). When the cutoff value was 140 mmHg, the rate of average target SBP achievement was 71.2% (703/987) at one month, 66.7% (618/927) during 1st to 12th month and 65.1% (542/832) from the first year to the third year after TEVAR. The proportion of patients taking≥2 antihypertensive agents was higher in the group of target blood pressure non-achievement group than the target blood pressure achievement group after TEVAR at 1 month (74.3% (211/284) vs.65.9% (463/703), P=0.010) and during 1st to 12th month (71.5% (221/309) vs. 63.6% (393/618), P=0.016). There were no statistical differences in the all-cause deaths, stroke, aortic related adverse events, and repeat TEVAR between the two groups (All P>0.05) during above follow-up periods. When the cutoff value was 150 mmHg, the rate of target SBP achievement was 89.3% (881/987) at one month, 85.2% (790/927) during 1st to 12th month and 85.6%(712/832) from the first year to the third year after TEVAR. The incidence of clinical total adverse events (8.8% (12/137) vs. 4.2% (33/790), P=0.021) and repeat TEVAR (4.4% (6/137) vs. 1.0% (8/790), P=0.003) in target blood pressure non-achievement group were significantly higher than the target blood pressure achievement group during 1st to 12th month after TEVAR. The incidence of all-cause deaths (5.8% (7/120) vs. 2.4% (17/712), P=0.037) in the target blood pressure non-achievement group was significantly higher than the target blood pressure achievement group from the first year to the third year follow-up period, but there were no statistical differences in the incidence of clinical total adverse events between the two group (P>0.05). Conclusion: Among TEVAR treated AAS patients complicated with hypertension, the average SBP more than 150 mmHg post discharge is associated with increased risk of adverse events. Ideal blood pressure control should be encouraged to improve the outcome of these patients.

Clinical characteristics and prognostic analysis of female patients with Stanford type B aortic dissection / 中华心血管病杂志

Objective: To explore the clinical characteristics and prognostic factors of female patients with Stanford type B aortic dissection. Methods: This is a single-centre retrospective study. Consecutive patients diagnosed with Stanford type B aortic dissection in General Hospital of Northern Theater Command from June 2002 to August 2021 were enrolled, and grouped based on sex. According to the general clinical conditions and complications of aortic dissection tear, patients were treated with thoracic endovascular aortic repair, surgery, or optimal medication. The clinical characteristics and aortic imaging data of the patients at different stages were collected, adverse events including all-cause deaths, stroke, and occurrence of aortic-related adverse events were obtained during hospitalization and within 30 days and at 1 and 5 years after discharge. According to the time of death, death was classified as in-hospital death, out-of-hospital death, and in-hospital death was divided into preoperative death, intraoperative death and postoperative death. According to the cause of death, death was classified as aortic death, cardiac death and other causes of death. Aortic-related adverse events within 30 days after discharge included new paraplegia, post-luminal repair syndrome, and aortic death; long-term (≥1 year after discharge) aortic-related adverse events included aortic death, recurrent aortic dissection, endoleak and distal ulcer events. The clinical characteristics, short-term and long-term prognosis was compared between the groups. Logistic regression analysis was used to explore the association between different clinical factors and all-cause mortality within 30 days in female and male groups separately. Results: A total of 1 094 patients with Stanford type B aortic dissection were enrolled, mean age was (53.9±12.1) years, and 861 (78.7%) were male and 233 (21.3%) were female. (1) Clinical characteristics: compared with male patients, female patients were featured with older average age, higher proportion of aged≥60 years old, back pain, anemia, optimal medication treatment, and higher cholesterol level; while lower proportion of smoking and drinking history, body mass index, calcium antagonists use, creatine kinase level, and white blood cell count (all P<0.05). However, there was no significant difference in dissection tear and clinical stage, history of coronary heart disease, diabetes, hypertension, and cerebrovascular disease between female and male patients (all P>0.05). (2) Follow-up result: compared with male patients, female patients had a higher rate of 30-day death [6.9% (16/233) vs. 3.8% (33/861), P=0.047], in-hospital death (5.6% (13/233) vs. 2.7% (23/861), P=0.027), preoperative death (3.9% (9/233) vs. 1.5% (12/861), P=0.023) and aorta death (6.0% (14/233) vs. 3.1% (27/861), P=0.041). The 1-year and 5-year follow-up results demonstrated that there were no significant differences in death, cerebrovascular disease, and aorta-related adverse events between the two groups (all P>0.05). (3) Prognostic factors: the results of the univariate logistic regression analysis showed that body mass index>24 kg/m2 (HR=1.087, 95%CI 1.029-1.149, P=0.013), history of anemia (HR=2.987, 95%CI 1.054-8.468, P=0.032), hypertension (HR=1.094, 95%CI 1.047-1.143, P=0.040) and troponin-T>0.05 μg/L (HR=5.818, 95%CI 1.611-21.018, P=0.003)were associated with an increased risk of all-cause mortality within 30 days in female patients. Conclusions: Female patients with Stanford type B aortic dissection have specific clinical characteristics, such as older age at presentation, higher rates of anemia and combined back pain, and higher total cholesterol levels. The risk of death within 1 month is higher in female patients than in male patients, which may be associated with body mass index, hypertension, anemia and troponin-T, but the long-term prognosis for both female and male patients is comparable.

Sciatic nerve derived exosomes in promotion of axon regeneration and functional recovery following peripheral nerve injury in rat / 中华显微外科杂志

Objective:To explore the effect of sciatic nerve derived exosomes(SN-EXO) on axon regeneration and functional recovery after peripheral nerve injury(PNI).Methods:From March 2021 to October 2022, the Department of Orthopedics of the First Affiliated Hospital of Zhengzhou University studied the effect of SN-EXO on the proliferation of Schwann cells(SCs) through EdU cell proliferation experiment. Twenty-one healthy male SD rats were randomly divided into 3 groups of sham operation, peripheral nerve injury(PNI) and SN-EXO treatment, with 7 rats in each group. The right sciatic nerves of rat models in sham group were exposed without injury. In the rat in PNI group and SN-EXO treatment group, PBS and SN-EXO were injected under the epineurium of right sciatic nerves following sciatic nerve crush. Sciatic nerve function index(SFI) was performed at 28 days after operation, and then sacrificed. Right sciatic nerves were removed for further exploration of nerve regeneration. The histopathological changes and axon arrangement of sciatic nerves were evaluated by HE staining. Regeneration efficiency of neurofilaments and SCs were obserred by NF200 and S100β double staining of sciatic nerve. The data obtained were statistically analyzed, and P<0.05 was statistically significant. Results:It was found that SN-EXO can significantly enhance the proliferation ability of SCs, with statistically significant difference( P<0.05). SFI in SN-EXO treatment group and PNI group were(-27.65±4.36) and(-57.33±7.49), respectively, and the difference was statistically significant( P<0.05). Axons in SN-EXO treatment group were arranged more closely and orderly than those in the PNI group at 28 days after operation, and there were less injury induced axon disintegration and vacuolation. Immunofluorescence assay indicated that NF200 and S100β fluorescence intensity in SN-EXO treatment group was significantly higher than that in the PNI group, and the difference was statistically significant( P<0.05). Conclusion:SN-EXO could enhance the proliferation of SCs to promote axon regeneration following peripheral nerve injury.

Fully understand COVID-19 related eye damage to improve the level of diagnosis and treatment / 中华实验眼科杂志

The continuous pandemic coronavirus disease 2019 (COVID-19) in the world has had a profound impact on the global medical model.More accumulated new medical data suggest that severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) infection will invade multiple organs of patients, but there is still a lack of sufficient understanding of the characteristics of ocular related lesions and their prognosis.The existing clinical data found that COVID-19-related ocular diseases mainly include ocular surface inflammatory lesions and retinopathy and choroidopathy in the posterior segment.The disease is not only an acute inflammatory reaction process, but also can lead to the pathological process of microvascular thrombosis in the retina and choroid, which may have a long-term impact on the visual prognosis of patients, especially those who were initially diagnosed as ophthalmic manifestations.Accurate diagnosis of COVID-19-related ocular diseases is a challenge for ophthalmologists.Ophthalmologists should have a deep understanding of the pathogenesis and development of SARS CoV-2 infected eyes, make use of the current multimodal ophthalmic imaging examination to reduce misdiagnosis and take timely targeted treatment measures to minimize the risk of disease damage to visual function.We suggest that clinical ophthalmologists pay attention to carry out the pathogenesis research of related diseases and multidisciplinary clinical research to reduce the blindness rate of patients with SARS CoV-2 infection and improve patients' quality of life.

The Action Effect of Two Kinds of Lumbar Massage Obliquity Manipulation with Different Lumbar Degeneration Degrees: A Comparative Study / 医用生物力学

Objective To compare the action effect of traditional and modified lumbar massage obliquity manipulation with different degrees of lumbar degeneration. Methods The biomechanical model of quality-spring-damping system lumbar spine was established and massage forces from professional massage doctors were collected. The force was used as input of the model, and lumbar degeneration was simulated by increasing elastic coefficient of the spring and damping coefficient of the damping in the model. By using MATLAB/ Simulink simulation technology, the effects of massage obliquity manipulation ( the maximum relative displacement and maximum acceleration) with different degrees of lumbar degeneration were obtained for comparative analysis.Results When the lumbar spine was degenerative, the maximum relative displacement and maximum acceleration of each segment were obtained under two manipulations. With the increase of lumbar degenerationdegree, the maximum relative displacement and maximum acceleration of each segment under two manipulations showed a downward trend, and the attenuation rate of the maximum relative displacement and maximum acceleration of each segment under two manipulations was obtained. Conclusions When degenerative changes in the spine do not occur, the effectiveness of traditional lumbar massage obliquity manipulation is slightly better than that of modified lumbar massage obliquity manipulation, but the safety of modified lumbar massage obliquity manipulation is obviously better than that of the traditional lumbar massage obliquity manipulation, so the modified lumbar massage obliquity manipulation should be used. With the aggravation of lumbar degeneration, the action effects of two manipulations are attenuated in a power function. The attenuation rate of effectiveness of modified lumbar massage obliquity manipulation is significantly faster than that of traditional lumbar massage obliquity manipulation, indicating that the modified lumbar massage obliquity manipulation should not be used in the caseof lumbar degeneration.

Protein phosphorylation involved in psychedelic-induced head-twitch response in rats / 中国药理学通报

Aim To investigate the potential protein post-translational modifications of psychedelic-induced Head-twith response and underling mechanism. Methods Psychedelics LSD, DOM, or Psilocin was administered to rats by intraperitoneal injection to induce head-twitch response, then the most effective dosage was identified to create animal models of head-twitch behavior. Western blot was performed in detecting the protein phosphorylation, acetylation, and ubiquitination in prefrontal cortex of SD rats after 10 min or 30 min injection. Results LSD (0.025 mg • kg~, i. p.), DOM (3 mg•kg

Risk factors analysis of protein energy wasting in children with chronic kidney disease / 中华儿科杂志

Objective: To analyze the clinical characteristics and risk factors of protein energy wasting (PEW) in children with chronic kidney disease (CKD). Methods: Clinical data of 231 children with chronic kidney disease hospitalized in Beijing Children's Hospital affiliated to Capital Medical University from January 2018 to January 2023 were retrospectively analyzed to explore the incidence of PEW. According to the diagnostic criteria of CKDPEW, they were divided into a CKDPEW group and a non PEW group. The comparison between the groups was performed by independent-sample t test and Chi-squared test, and the risk factors were analyzed by multivariate Logistic regression. Results: Among the 231 children, there were 138 males and 93 females, with a visiting age of 9.9 (7.9, 16.0) years; 6 cases were in stage 1, 14 cases in stage 2, 51 cases in stage 3, 36 cases in stage 4, and 124 cases in stage 5. A total of 30 children (13.0%) with CKD PEW were diagnosed at the age of 7. 1 (3.8, 13.2) years, including 1 case in stage 1, 1 case in stage 2, 5 cases in stage 3, 5 cases in stage 4, and 18 cases in stage 5. There were a total of 201 cases (87.0%) in the non PEW group, diagnosed at the age of 11.8 (8.5, 12.2) years, including 5 cases in stage 1, 13 cases in stage 2, 46 cases in stage 3, 31 cases in stage 4, and 106 cases in stage 5. The Chi-squared test and t test showed that the systolic blood pressure, diastolic blood pressure, birth weight and carbon dioxide binding capacity of the CKD PEW group were lower than those of the non PEW group ((109±22) vs. (120±20) mmHg (1 mmHg=0.133 kPa), (72±19) vs. (79±16) mmHg, (2.9±0.5) vs. (3.2±0.6) kg, (17±4) vs. (19±4) mmol/L,t=2.85, 2.14, 0.67, 2.63, all P<0.05). Multivariate logistic regression analysis showed that carbon dioxide binding capacity and birth weight were independent protective factors of CKDPEW in children (OR=0.81 and 0.36, 95%CI=0.73-0.90 and 0.17-0.77, respectively; both P<0.01); the risk of PEW in CKD children decreased by 0.187 times for every 1 mmol/L increment in carbon dioxide binding capacity, and 0.638 times for every 1 kg increment in birth weight. Conclusions: The incidence of protein energy expenditure in children with chronic kidney disease is lower than that in the previous researches. PEW can appear in CKD 1-2 stage, and attention should be paid to it in the early stage of CKD in clinical practice. Low birth weight CKD children are susceptible to PEW, and actively correcting metabolic acidosis can reduce the risk of CKDPEW.

Changes of uterine morphology and endometrial T2 signal intensity in the fibrotic repair secondary to endometrial injury / 中华妇产科杂志

Objective: To investigate the value of uterine morphological parameters and endometrial T2 signal intensity (T2-SI) in evaluating the degree of the fibrotic repair secondary to endometrial injury. Methods: From Sep. 2018 to Feb. 2023, this study prospectively enrolled 29 patients with fibrotic repair secondary to severe endometrial injury (severe group), 17 patients with fibrotic repair secondary to mild to moderate endometrial injury (mild to moderate group), and 40 healthy women of reproductive age (control group) in Nanjing Drum Tower Hospital. The length of uterine cavity (LUC), length of cervix and isthmus (LCI), width of upper uterine cavity (WUUC) and width of lower uterine cavity (WLUC) were measured using magnetic resonance imaging. T2-SI of endometrium and subcutaneous fat of buttocks were measured, and endometrial normalized T2-SI (nT2-SI; T2-SI of endometrium/T2-SI of subcutaneous fat of buttocks) was calculated. Statistical analyses of data were performed using one-way analysis of variance, Mann-Whitney U test, intraclass correlation coefficient, Spearman rho test, area under the receiver operating characteristic curve (AUC). Results: LUC, WUUC, WLUC and endometrial nT2-SI of severe group [(19.7±3.5) mm, (26.9±6.4) mm, (7.9±1.4) mm, 0.73±0.11, respectively] were significantly lower than those of the control group (all P<0.01), while LCI and WUUC/LUC [(51.3±7.3) mm and 1.38±0.34] were significantly higher than those of the control group (all P<0.001). LUC and WLUC of severe group were significantly lower than those of mild to moderate group [(32.4±5.1) mm and (8.8±1.2) mm; all P<0.05], while LCI and WUUC/LUC were significantly higher than those of mild to moderate group [(41.8±8.6) mm and 0.94±0.16; all P<0.001]. LUC and endometrial nT2-SI of mild to moderate group were significantly lower than those of the control group [ (32.4±5.1) vs (35.3±3.5) mm, 0.68±0.13 vs 0.80±0.12; all P<0.01]. LUC, WUUC, WLUC and endometrial nT2-SI were significantly negatively correlated to the degree of the fibrotic repair secondary to endometrial injury (Spearman rho:-0.794, -0.441, -0.471 and -0.316, respectively; all P<0.05), while LCI and WUUC/LUC were significantly positively correlated to the degree of the fibrotic repair secondary to endometrial injury (Spearman rho: 0.481 and 0.674, respectively; all P<0.05). LUC and WUUC/LUC showed high value in distinguishing severe group from the control group or mild to moderate group (all AUC>0.9, all P<0.001). Conclusion: As noninvasive and quantitative biomarkers, uterine morphological parameters and endometrial nT2-SI could evaluate the degree of the fibrotic repair secondary to endometrial injury.

Effect of Gegen Qinliantang on SIRT1/FoxO1 Autophagy Pathway in db/db Diabetic Mice / 中国实验方剂学杂志

ObjectiveTo validate the alleviating effect of Gegen Qinliantang （GGQLT） on insulin resistance in db/db diabetic mice by regulating the silent information regulator 1 （SIRT1）/forkhead transcription factor O1 （FoxO1） autophagy pathway. MethodSeventy-five SPF-grade spontaneous type 2 diabetic db/db mice and 15 control db/m mice were selected and maintained on regular feed for one week before measuring blood glucose. They were randomly divided into six groups， with 15 mice in each group. The groups included a normal group （physiological saline， 0.2 g·kg-1）， a metformin group （0.2 g·kg-1）， high-， medium-， and low-dose GGQLT groups （31.9， 19.1， 6.9 g·kg-1）， and a model group （physiological saline， 0.2 g·kg-1）. They were orally treated with corresponding drugs for eight weeks， once daily. Fasting blood glucose （FBG） was measured using a Roche glucometer. Serum levels of high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， triglyceride （TG）， and total cholesterol （TC） were measured using an automated biochemical analyzer. Fasting serum insulin （INS） levels were determined using enzyme-linked immunosorbent assay （ELISA）， and the homeostasis model assessment of insulin resistance （HOMA-IR） was calculated. Western blot was used to detect the expression of Beclin-1， microtubule-associated protein 1 light chain 3 （LC3）， and SIRT1/FoxO1 autophagy pathway-related proteins in liver tissues. Immunohistochemistry was performed to assess the expression of SIRT1， FoxO1， Beclin-1， and LC3B proteins in liver tissues. Transmission electron microscopy was used to observe the formation of autophagosomes in the liver. ResultCompared with the normal group， the model group showed significant increases in FBG， FINS， HOMA-IR， TC， TG， LDL-C， and HDL-C levels （P<0.01）， and significant increases in the expression of SIRT1， Beclin-1， LC3， and FoxO1 proteins in liver tissues （P<0.01）. Transmission electron microscopy revealed the highest number of autophagosomes in the model group. Compared with the model group， the metformin group and the low-， medium-， and high-dose GGQLT groups showed significant decreases in serum FBG， FINS， HOMA-IR， TC， TG， LDL-C， and HDL-C levels （P<0.05， P<0.01）， significant decreases in the expression of SIRT1， Beclin-1， LC3 （P<0.05， P<0.01）， and up-regulated FoxO1 protein （P<0.01）. Transmission electron microscopy showed a reduction in the degree of autophagy in the treatment groups. Compared with the metformin group， the medium- and high-dose GGQLT groups showed significant decreases in FBG， FINS， and TG levels （P<0.01）， significant decreases in the expression of SIRT1， Beclin-1， and LC3 in liver tissues （P<0.05， P<0.01）， and reduced FoxO1 protein （P<0.01）. The high-dose GGQLT group showed reduced HOMA-IR， TC， LDL-C， and HDL-C levels （P<0.05， P<0.01）. Transmission electron microscopy revealed a significant reduction in autophagosomes in the medium- and high-dose GGQLT groups. ConclusionGGQLT can significantly improve glucose and lipid metabolism disorders， alleviate insulin resistance in db/db mice， and prevent and treat type 2 diabetes by activating the SIRT1/FoxO1 autophagy pathway.

Inhibitory Effect of Resveratrol on the Proliferation of Multiple Myeloma Cells and the Underlying Mechanism / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of resveratrol (RSV) on the proliferation of multiple myeloma (MM) cells and its molecular mechanism.@*METHODS@#MM cells (MM1.S, RPMI-8226 and U266) were treated with different concentrations of RSV for 24-72 h. The effect of RSV on the proliferation of MM cells was detected by CCK-8 (cell counting kit-8) assay. RPMI-8226 cells were divided into RSV, miR-21 mimic, RSV+miR-21 mimic, miR-21 inhibitor and RSV+miR-21 inhibitor groups, and transfected with corresponding plasmids. The cell cycle distribution of each group was detected by flow cytometry with propidium iodide (PI) single staining. The cell apoptosis of each group was detected by AnnexinV-FITC/PE-PI double staining. The expression of miR-21 in MM cells treated with RSV and the expression of KLF5 mRNA in each group were detected by qRT-PCR. The expression of KLF5 protein in each group was detected by Western blot.@*RESULTS@#RSV inhibited the proliferation and induced apoptosis of MM cells in a time- and dose-dependent manner. After the MM cells were treated with RSV, the number of cells in sub-G1 phase was increased, and that in G2/M phase was decreased. Moreover, RSV significantly downregulated the expression of miR-21 in MM cells, and the inhibitory effect of miR-21 mimic on KLF5 expression in MM cells was counteracted by RSV.@*CONCLUSION@#RSV may inhibit the proliferation and induce apoptosis of MM cells by inhibiting miR-21 and up-regulating KLF5 expression.

Comparison of effectiveness of lower extremity axial distractor and traction table assisted closed reduction and intramedullary nail fixation in femoral subtrochanteric fracture / 中国修复重建外科杂志

OBJECTIVE@#To compare the effectiveness of lower extremity axial distractor (LEAD) and traction table assisted closed reduction and intramedullary nail fixation in treatment of femoral subtrochanteric fracture.@*METHODS@#The clinical data of 117 patients with subtrochanteric fracture of femur treated by closed reduction and intramedullary nail fixation between May 2012 and May 2022 who met the selection criteria were retrospectively analyzed. According to the auxiliary reduction tools used during operation, the patients were divided into LEAD group (62 cases with LEAD reduction) and traction table group (55 cases with traction table reduction). There was no significant difference in baseline data, such as gender, age, injured side, cause of injury, fracture Seinsheimer classification, time from injury to operation, and preoperative visual analogue scale (VAS) score, between the two groups ( P>0.05). Total incision length, operation time, intraoperative blood loss, fluoroscopy frequency, closed reduction rate, fracture reduction quality, fracture healing time, weight-bearing activity time, and incidence of complications, as well as hip flexion and extension range of motion (ROM), Harris score, and VAS score at 1 month and 6 months after operation and last follow-up were recorded and compared between the two groups.@*RESULTS@#There were 14 cases in the LEAD group from closed reduction to limited open reduction, and 43 cases in the traction table group. The incisions in the LEAD group healed by first intention, and no complication such as nerve and vascular injury occurred during operation. In the traction table group, 3 cases had perineal crush injury, which recovered spontaneously in 1 week. The total incision length, operation time, intraoperative blood loss, fluoroscopy frequency, and closed reduction rate in the LEAD group were significantly better than those in the traction table group ( P<0.05). There was no significant difference in the quality of fracture reduction between the two groups ( P>0.05). Patients in both groups were followed up 12-44 months, with an average of 15.8 months. In the LEAD group, 1 patient had delayed fracture union at 6 months after operation, 1 patient had nonunion at 3 years after operation, and 1 patient had incision sinus pus flow at 10 months after operation. In the traction table group, there was 1 patient with fracture nonunion at 15 months after operation. X-ray films of the other patients in the two groups showed that the internal fixator was fixed firmly without loosening and the fractures healed. There was no significant difference in fracture healing time, weight bearing activity time, incidence of complications, and postoperative hip flexion and extension ROM, Harris score, and VAS score at different time points between the two groups ( P>0.05).@*CONCLUSION@#For femoral subtrochanteric fracture treated by close reduction and intramedullary nail fixation, compared with traction table, LEAD assisted fracture reduction can significantly shorten the operation time, reduce intraoperative blood loss and fluoroscopy frequency, reduce incision length, effectively improve the success rate of closed reduction, and avoid complications related to traction table reduction. It provides a new method for good reduction of femoral subtrochanteric fracture.

Research progress in epigenetic pharmacological effects of rhein / 中国中药杂志

Rhein, which is one of the main active components of Rheum palmatum, has a range of pharmacological activities such as the regulation of the metabolism of glucose and lipids, anti-inflammatory, anti-tumor, anti-fibrosis, etc. Epigenetics refers to the heritable variation of gene expression without altering the DNA sequence. It is involved in the emergence and development of inflammation, renal fibrosis, diabetes, cancer, atherosclerosis, and other diseases, thus becoming a new strategy for the treatment of many di-seases. A series of studies have shown that epigenetic modification may be a common molecular mechanism of various pharmacological effects of rhein. This paper summarized the effects of rhein on the regulation of epigenetic modification and its underlying mechanisms, which involve the regulation of DNA methylation, protein acetylation, and RNA methylation, so as to provide a basis for the development and application of rhein.

Chromatin Remodeling Factor SMARCA5 is Essential for Hippocampal Memory Maintenance via Metabolic Pathways in Mice / 神经科学通报·英文版

Gene transcription and new protein synthesis regulated by epigenetics play integral roles in the formation of new memories. However, as an important part of epigenetics, the function of chromatin remodeling in learning and memory has been less studied. Here, we showed that SMARCA5 (SWI/SNF related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 5), a critical chromatin remodeler, was responsible for hippocampus-dependent memory maintenance and neurogenesis. Using proteomics analysis, we found protein expression changes in the hippocampal dentate gyrus (DG) after the knockdown of SMARCA5 during contextual fear conditioning (CFC) memory maintenance in mice. Moreover, SMARCA5 was revealed to participate in CFC memory maintenance via modulating the proteins of metabolic pathways such as nucleoside diphosphate kinase-3 (NME3) and aminoacylase 1 (ACY1). This work is the first to describe the role of SMARCA5 in memory maintenance and to demonstrate the involvement of metabolic pathways regulated by SMARCA5 in learning and memory.

Did Chinese children with imaginary companions attribute more agencies to non-human items: Evidences from behavioral cues and appearance characteristics.

Previous studies have focused on the relationship between imaginary companions (ICs) and children's social developments. As far as we know, few studies have focused on the relationship between ICs and children's agency attributions. This study aimed to explore the potential differences in agency attributions between children with and without ICs, children with egalitarian IC relationships and hierarchical IC relationships. Children's agency attributions were measured by two experiments. One was based on behavioral cues (Random animations/ToM animations) and the other was based on appearance characteristics (ball/doll). The results revealed that children with ICs attributed more cognitive properties to Random and ToM animations than children without ICs. Compared with children without ICs, children with ICs attributed marginally more biological properties to a ball and more psychological properties to a ball and a doll. However, children with egalitarian and hierarchical IC relationships did not differ in their agency attributions. The results suggest that children with ICs are more likely to attribute agencies to non-human items with behavioral cues or appearance characteristics than children without ICs. Compared with child-IC relationship qualities, IC status may be more related to children's agency attributions. However, only a correlation between IC status and children's agency attributions was found in this study and it is interesting for future researchers to investigate the potential causal directions between children's IC status and their agency attributions. If one of the causal directions or both the causal directions exist, future researchers can further explore the underlying mechanism.

Attention to renal involvement: report of 17 Joubert syndrome cases in children of a single center in China.

BACKGROUND: Joubert Syndrome (JS) is a rare genetic developmental disorder. We are aiming for increasing awareness of this disease especially kidney involvement in children with JS. METHODS: Clinical and genetic data of 17 cases of JS in Beijing children's hospital in the past 21 years were collected retrospectively. RESULTS: Twelve males and 5 females, aged from 12d to 15y8m. The most common involvement was neurological system involvement. The second most common involvement was renal involvement: end stage kidney disease in 6 cases (35%), hematuria in 5 cases (29%), proteinuria in 5 cases (29%), renal diffuse lesions in 4 cases (24%), renal cystic lesions in 2 cases (12%), and echogenic enhancement of parenchyma in 2 cases (12%). 10 cases did genetic tests. 3 cases with renal deficiency all had RPGRIP1L gene mutation. CONCLUSIONS: The most common involvement of JS is neurological involvement, and the second is renal involvement. Pediatricians should improve awareness of JS and conduct systemic evaluation of children. More attention should be paid to renal involvement which may be onset hidden but fatal. Early recognition and diagnosis are the goals to delay the start to dialysis and improve quality of patients' life. The RPGRIP1L gene mutation maybe the most common gene mutation in JS and may have correlations with renal involvement.

A gradient-based discriminant analysis method for process quality control of carbonized TCM via Fourier transform near infrared spectroscopy: A case study on carbonized Typhae Pollen.

Carbonized traditional Chinese medicine (TCM) is a kind of distinctive traditional drug which has been widely used in various bleeding syndromes for over two thousand years, and most of them are still in clinical use. Although they share similar processing method: stir-frying, there are no specific quality standards and few quality control researches carried out on carbonized TCM up until now. Carbonized Typhae Pollen (CTP) is a typical carbonized TCM with efficacy of eliminating blood stasis and stanching bleeding. In this study, a novel process quality control model coupled with near infrared spectroscopy was established, called Gradient-based Discriminant Analysis method (GDA). Compared with conventional modeling methods (Convolutional Neural Network, Linear Discriminant Analysis, Standard Normal Variate-LDA), GDA model applied in fiber optic probe acquisition mode exhibited highest test accuracy (0.961), satisfactory correct identification (internal validation, 100%; external validation, 97.1%) and excellent model stability. This method provided a perfect guideline for process quality control of Carbonized TCM as well as ensured their clinical efficacy.

Chemical constituents of Scrophulariae Radix and their antitumor activities in vitro / 中国中药杂志

The present study investigated the chemical constituents of Scrophulariae Radix and their antitumor activities in vitro. The compounds in the ethyl acetate extract were separated and purified by conventional column chromatographies(such as silica gel, Sephadex LH-20, and ODS column) and semi-preparative high-performance liquid chromatography(HPLC), and their structures were identified by various spectral techniques such as nuclear magnetic resonance(NMR) and mass spectrometry(MS). Twenty-three compounds were isolated and identified as benzyl-β-D-(3',6'-di-O-acetyl) glucoside(1), 5-O-p-methoxybenzoyl kojic acid(2), 5-O-methoxybenzoyl kojic acid(3), 7-O-methylbenzoyl kojic acid(4), 5-O-benzoyl kojic acid(5), methyl ferulate ethyl ether(6), trans-ferulic acid(7), trans-isoferulic acid(8), trans-caffeic acid(9), trans-caffeic acid methyl ester(10), caffeic acid ethyl ester(11), trans-cinnamic acid(12), trans-p-methoxycinnamic acid(13), trans-p-hydroxycinnamic acid(14), trans-p-hydroxycinnamic acid methyl ester(15), 2-(3,4-dihydroxyphenethyl) alcohol(16),(p-hydroxyphenyl) propanoic acid(17), coniferaldehyde(18), sinapaldehyde(19), benzyl β-primeveroside(20), 5-(hydroxymethyl) furfural(21), furan-2-carboxylic acid(22), and decanedioic acid(23). Among them, compound 1 is a new benzyl glucoside, compounds 2-4 are new pyranone compounds, compound 5 is a new natural product of pyranone. The NMR data of compounds 5 and 6 are reported for the first time. Compounds 6 and 20 were isolated from the Scrophularia plant for the first time. Compounds 8, 11, 14, 16, 18, 19, 22, and 23 were isolated from this plant for the first time. The in vitro cytotoxic activities of these compounds against three tumor cell lines(HepG2, A549, and 4 T1) were evaluated. The results showed that compounds 10 and 15 showed cytotoxic activities against HepG2 cells with IC_(50) values of(19.46±0.48) μmol·L~(-1) and(46.10±1.21) μmol·L~(-1).

Analysis of metabolites of rocuronium bromide in human bile and the study of transmembrane transport mechanism / 药学学报

Rocuronium bromide is an acetylcholine N2 receptor antagonist, which can be used as an auxiliary drug for general anesthesia. It has been reported that rocuronium has two possible metabolic pathways: N-dealkylation and O-deacetylation, which are mainly taken up by liver and excreted by bile in the form of primary drugs. In this paper, the metabolites of rocuronium in human bile were detected by UHPLC-QE-orbitrap-MS, thirteen metabolites were detected, including eleven phase I metabolites and two phase II metabolites, eleven of which had not been previously reported. At the same time, HEK293 cells overexpressing transporter were used to explore the transmembrane transport mechanism of rocuronium, the results showed that rocuronium was the substrate of MATE1, OCT1, OATP1B1 and OATP1B3. The above research results enrich the metabolic pathway of rocuronium in vivo, and put forward the possible transport mechanism of liver uptake and bile excretion, which can better guide the accurate and safe clinical drug application. The collection of human bile samples in this study was approved by the ethics committee of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (Approval Number: 2019-775-130-01).