Objective To conduct the biomechanical analysis on a new power-assisted knee orthosis.Methods A self-force source power-assisted knee orthosis was used,and four motions(level walking,sitting and standing,ascending and descending stairs)were measured before and after wearing the orthosis.A musculoskeletal multibody dynamic model was adopted to calculate the joint angles and pressures at the knee,patellofemoral and hip joints.The effects of power-assisted knee orthosis on biomechanical changes of lower limbs were investigated by comparing the joint angles and pressures before and after wearing this orthosis.Results The orthosis would reduce the knee angles during level walking,as well as the knee pressures during sitting and standing on the wearing side.Wearing the orthosis did not significantly affect the joint angles during sitting and standing;however,it led to a significant decrease in joint pressures at both bilateral knee joints and patellofemoral joints.During ascending and descending stairs,the knee angle change on the wearing side was opposite to that on the non-wearing side.The increase of the peak knee angle was(14.3±3.6)%on the non-wearing side during ascending stairs.Conclusions The power-assisted knee orthosis can offer a conservative treatment for individuals with various knee diseases by reducing joint angles and pressures in daily motions.

Objective To conduct the biomechanical analysis on a new power-assisted knee orthosis.Methods A self-force source power-assisted knee orthosis was used,and four motions(level walking,sitting and standing,ascending and descending stairs)were measured before and after wearing the orthosis.A musculoskeletal multibody dynamic model was adopted to calculate the joint angles and pressures at the knee,patellofemoral and hip joints.The effects of power-assisted knee orthosis on biomechanical changes of lower limbs were investigated by comparing the joint angles and pressures before and after wearing this orthosis.Results The orthosis would reduce the knee angles during level walking,as well as the knee pressures during sitting and standing on the wearing side.Wearing the orthosis did not significantly affect the joint angles during sitting and standing;however,it led to a significant decrease in joint pressures at both bilateral knee joints and patellofemoral joints.During ascending and descending stairs,the knee angle change on the wearing side was opposite to that on the non-wearing side.The increase of the peak knee angle was(14.3±3.6)%on the non-wearing side during ascending stairs.Conclusions The power-assisted knee orthosis can offer a conservative treatment for individuals with various knee diseases by reducing joint angles and pressures in daily motions.

Morita therapy has been bom for more than 100 years.Inpatient Morita therapy is highly oper-able and easy to master.It can improve many refractory neuroses through four-stage treatment.But more neuroses are treated in outpatient clinics,and Morita therapy cannot be used in hospitalized patients.Therefore,the formula-tion of expert opinions on outpatient operations is particularly important.This paper is based on domestic and for-eign references,and after many discussions by domestic Morita therapy experts,and then drew up the first version of the expert opinions on operation of outpatient Morita therapy.Meanwhile the operation rule of Morita therapy in three stages of outpatient treatment was formulated:in the etiological analysis stage,under the theoretical guidance of Morita therapy,analyze the pathogenic factors,to improve treatment compliance and reduce resistance;during the operating stage,guide patients to engage in constructive and meaningful actions,realizing the achievement of letting nature take its course principle;in the cultivating character and enriching life stage,pay attention to positive infor-mation,expanding the scope and content of actions,improving the ability to adapt to complex life,and preventing recurrence caused by insufficient abilities.It will lay a foundation for the promotion of Morita therapy in domestic outpatient clinics,so that more patients with neurosis and other psychological diseases could receive characteristic Morita therapy treatment in outpatient clinics.

【Objective】 To explore the clinical characteristics and risk factors of renal function deterioration in children with renal dysplasia and chronic kidney disease (CKD), so as to provide a basis for the diagnosis, treatment, and management. 【Methods】 The clinical data of children with renal dysplasia complicated with CKD treated in the Children’s Hospital of Chongqing Medical University during 2012 and 2022 were retrospectively analyzed, including the gender, age of diagnosis, growth index, concomitant malformation and complications. According to the diagnostic criteria and staging standard of KDIGO2020 guidelines, patients with disease deteriorated to CKD stage 4-5 were enrolled into the regression group. Factors affecting the deterioration of renal function were determined with Cox regression analysis. 【Results】 A total of 122 children were involved, including 66 (54.1%) with CKD stag 4-5. There were more boys than girls. Bilateral and unilateral renal dysplasia occurred in 88 (72.13%) and 34 (27.87%) cases, respectively, and 64 (52.46%) cases were complicated with other urinary diseases. There were significant differences in weight, height and body mass index (BMI) among patients with CKD stage 1-5 (P<0.01). The age of onset of CKD <10 years, BMI lower than the 3rd percentile of the same sex and age, bilateral renal dysplasia, and one or more complications of congenital renal and urinary tract abnormalities (CAKUT) were the risk factors of deterioration of renal function (P<0.05). 【Conclusion】 Renal dysplasia complicated with CKD are more common in boys, with high incidence of bilateral renal dysplasia. Bilateral renal dysplasia, age of onset of CKD <10 years, BMI lower than 3% and complications are important influencing factors of renal dysplasia in children with CKD.

Postzygotic mutations are acquired in normal tissues throughout an individual's lifetime and hold clues for identifying mutagenic factors.Here,we investigated postzygotic mutation spectra of healthy individuals using optimized ultra-deep exome sequencing of the time-series samples from the same volunteer as well as the samples from different individuals.In blood,sperm,and muscle cells,we resolved three common types of mutational signatures.Signatures A and B represent clock-like mutational processes,and the polymorphisms of epigenetic regulation genes influence the pro-portion of signature B in mutation profiles.Notably,signature C,characterized by C＞T transitions at GpCpN sites,tends to be a feature of diverse normal tissues.Mutations of this type are likely to occur early during embryonic development,supported by their relatively high allelic frequencies,presence in multiple tissues,and decrease in occurrence with age.Almost none of the public datasets for tumors feature this signature,except for 19.6％of samples of clear cell renal cell carcinoma with increased activation of the hypoxia-inducible factor 1(HIF-1)signaling pathway.Moreover,the accumulation of signature C in the mutation profile was accelerated in a human embryonic stem cell line with drug-induced activation of HIF-1α.Thus,embryonic hypoxia may explain this novel signature across multiple normal tissues.Our study suggests that hypoxic condition in an early stage of embryonic development is a crucial factor inducing C＞T transitions at GpCpN sites;and indi-viduals'genetic background may also influence their postzygotic mutation profiles.

Objective:To find out predictors of the testicular ischemia caused by incarcerated inguinal hernia and evaluate the ischemic injury of the testis more accurately, which can indicate testicle exploration in time or prevent unnecessary testicle exploration.Methods:Pediatric patients (median: 9 months) undergoing operation of unilateral incarcerated inguinal hernia and ipsilateral testicular exploration from 1 Jul. 2013 to 30 Jun. 2019 were retrospectively investigated. Age at surgery, incarcerate duration, degree of intestinal and testicular injury, times of manual reduction and preoperative ultrasound data were collected. Statistical analysis was performed by SAS 9.4 (Copyright ? 2016 SAS Institute Inc.Cary, NC, USA) .Results:460 patients (median: 9 months) , of which 57 (12.39%) (median: 1.4 months, interquartile range 0.8-10.7 months) had severe testicular injury, and their average incarceration time was (23.9±9.3) h. Univariate logistic regression revealed that increased times of manual reduction, ultrasound scores, incarcerate duration and degree of intestinal injury were positively correlated with the degree of testicular ischemia, while age at surgery was negatively correlated with the degree of testicular ischemia ( P<0.05) . A model for calculating the probability of severe testicular ischemia injury was established: P= through multivariate analysis with backward stepwise logistic regression and 10-fold cross-validation was used for preliminary verification of the model. Conclusion:This study provides a relative reliable model to predict the risk of irreversible testicular ischemia due to incarcerated inguinal hernia using readily available clinical characteristics in young pediatrics with testicular ischemia.

Background::Asthma is a heterogeneous disease with distinct prevalence and manifestation between sexes. This study was to identify sex-specific features of asthma via metabolomic analysis of sphingolipids.Methods::Forty-two asthma patients (27 women and 15 men) admitted to the Peking University Third Hospital from January 2015 to December 2015 were enrolled. Peripheral venous blood was collected for metabolomic analysis by targeted liquid chromatography-mass spectrometry. Sex hormones(estradiol, progesterone, testosterone, and androstenedione) and multiple inflammatory factors (periostin, leptin, IgE, IL-4, IL-5, IL-10, IL-13, IL-17A, and IFN-γ) were also assessed. The eosinophil percentage in induced sputum was also detected. All these data were applied to comparative analysis between sexes.Results::Testosterone was negatively related to periostin ( ρ = -0.420, P = 0.009) and IL-5 ( ρ = -0.540, P = 0.012), while estradiol was positively related to the blood eosinophil percentage ( ρ = 0.384, P = 0.025). Among the eighteen species of sphingolipids detected in the 42 patients, five ceramide (Cer) species (Cer16:0, Cer:20:0, Cer22:0, Cer24:0, and Cer26:0) and one sphingomyelin (SM) species (SM38:0) were significantly higher in male than in female patients. Further investigation found that the correlation between Cer20:0 and IL-5 was positive in males ( ρ = 0.943, P = 0.005) but negative in females ( ρ = -0.561, P = 0.030). Conclusions::Testosterone was negatively correlated with eosinophil inflammatory factors, but estradiol was positively correlated. Male asthma patients had higher ceramide and sphingomyelin levels than female patients. Different sexes had opposite correlations with ceramide and IL-5, respectively, suggesting that therapeutic strategies targeting ceramide should be different between sexes.

Background::Asthma is a heterogeneous disease with distinct prevalence and manifestation between sexes. This study was to identify sex-specific features of asthma via metabolomic analysis of sphingolipids.Methods::Forty-two asthma patients (27 women and 15 men) admitted to the Peking University Third Hospital from January 2015 to December 2015 were enrolled. Peripheral venous blood was collected for metabolomic analysis by targeted liquid chromatography-mass spectrometry. Sex hormones(estradiol, progesterone, testosterone, and androstenedione) and multiple inflammatory factors (periostin, leptin, IgE, IL-4, IL-5, IL-10, IL-13, IL-17A, and IFN-γ) were also assessed. The eosinophil percentage in induced sputum was also detected. All these data were applied to comparative analysis between sexes.Results::Testosterone was negatively related to periostin ( ρ = -0.420, P = 0.009) and IL-5 ( ρ = -0.540, P = 0.012), while estradiol was positively related to the blood eosinophil percentage ( ρ = 0.384, P = 0.025). Among the eighteen species of sphingolipids detected in the 42 patients, five ceramide (Cer) species (Cer16:0, Cer:20:0, Cer22:0, Cer24:0, and Cer26:0) and one sphingomyelin (SM) species (SM38:0) were significantly higher in male than in female patients. Further investigation found that the correlation between Cer20:0 and IL-5 was positive in males ( ρ = 0.943, P = 0.005) but negative in females ( ρ = -0.561, P = 0.030). Conclusions::Testosterone was negatively correlated with eosinophil inflammatory factors, but estradiol was positively correlated. Male asthma patients had higher ceramide and sphingomyelin levels than female patients. Different sexes had opposite correlations with ceramide and IL-5, respectively, suggesting that therapeutic strategies targeting ceramide should be different between sexes.

Objective:To investigate the role of basic fibroblast growth factor (bFGF) in decreasing intracranial pressure in rats after intra-abdominal hypertension (IAH).Methods:A total of 60 healthy SD rats were selected for the experiment. Secondary IAH rat models were established by hemorrhagic shock/resuscitation, followed by injecting nitrogen into the peritoneal cavity of the rats to maintain an intra-abdominal pressure of 12mmHg and above. According to the random number table, the rats were divided into control group, IAH group, IAH+ bFGF group (bFGF group) and IAH+ bFGF+ PD173074 group (antagonist group), with 15 rats per group. Indicators were measured 4 hours after injury, including intracranial pressure, brain morphological observation, apparent diffusion coefficient (ADC) value, lactic acid content of brain MRI, brain water content and Evans blue exudation. Immunofluorescence staining, Western blotting and PCR were used to detect the expressions of phosphorylate-fibroblast growth factor receptor 1, 2 (p-FGFR1, 2), Zonula occludens-1 (ZO-1), β-catenin, matrix metalloproteinases 9 (MMP9), interleukin-1β (IL-1β) in brain microvascular endothelial cells (BMECs).Results:The intracranial pressure in IAH group [(5.52±0.45)mmHg] gradually increased 4 hours after injury compared control group [(3.36±0.30)mmHg]. Compared with IAH group, the intracranial pressurein bFGF group [(4.46±0.41)mmHg] was decreased ( P<0.05). Compared with bFGF group, the intracranial pressure in antagonist group [(5.36±0.44)mmHg] was enhanced ( P<0.05). Brain morphological observations in IAH group showed swelling and obvious cerebral edema, accompanied with a small amount of subarachnoid hemorrhage. Compared with IAH group, cerebral edema and brain swelling were relieved in bFGF group, while the antagonist group still showed cerebral edema and obvious brain swelling. At 4 hours after injury, MRI examination showed that the relative ADC value in IAH group (cortex: 0.82±0.11, corpus callosum: 1.26±0.17) was lower than that in control group (cortex: 1.00±0.13, corpus callosum: 1.43±0.15)( P<0.05). Compared with IAH group, the relative ADC value in bFGF group (cortex: 0.94±0.16, corpus callosum: 1.36±0.16) was increased ( P<0.05). Compared with bFGF group, the relative ADC value in antagonist group (cortex: 0.87±0.13, corpus callosum: 1.30±0.14) was decreased ( P<0.05). Relative lactic acid content in IAH group (cortex: 15.50±2.14, corpus callosum: 10.82±1.90)was higher than that in control group (cortex: 1.00±0.23, corpus callosum: 0.70±0.20)( P<0.05). Compared with IAH group, the relative lactic acid content in bFGF group (cortex: 10.85±1.42, corpus callosum: 6.96±1.30) was decreased ( P<0.05). Compared withbFGF group, the relative lactic acid content in antagonist group (cortex: 13.71±1.61, corpus callosum: 9.12±1.52) was increased ( P<0.05). The brain water content in IAH group [(87.9±0.8)%] was higher than that in control group [(76.3±0.9)%]. Compared with IAH group, the brain water content in bFGF group [(83.2±1.0)%] was decreased( P<0.05). Compared with bFGF group, the brain water content in antagonist group[(85.4±0.8)%] was increased ( P<0.05). Evans blue exudation in IAH group [(3.22±0.29)μg/ml] was greater than that in control group [(0.42±0.22)μg/ml]( P<0.05). Compared with IAH group, the Evans blue exudation in bFGF group [(2.04±0.25)μg/ml] was decreased ( P<0.05). Compared with bFGF group, the Evans blue exudation in antagonist group [(2.92±0.20)μg/ml] was increased ( P<0.05). Compared with control group, the expression of p-FGFR1 in BMECs in IAH group was weakened 4 hours after injury, but p-FGFR2 remained unchanged, the expressions of ZO-1, β-catenin protein and mRNA were weakened, and the expressions of MMP9, IL-1β protein and mRNA were enhanced ( P<0.05). Compared with IAH group, the expressions of p-FGFR1, ZO-1, β-catenin protein and mRNA were enhancedin bFGF group, and the expressions of MMP9, IL-1β protein and mRNA were weakened as well ( P<0.05). However, the expressions of p-FGFR1, ZO-1 and β-catenin protein and mRNA in antagonist group were weaker than those in bFGF group, and the expressions of MMP9 and IL-1β protein and mRNA were stronger than those in the bFGF group ( P<0.05). Conclusion:After IAH, the rat model presents damaged blood-brain barrier, increased cerebral edema, and increased intracranial pressure, and the use of bFGF can improve these symptoms. FGFR1 of BMECs is a key receptor for bFGF to play a protective role, and its receptor inhibitor PD173074 can attenuate the protective effect of bFGF.

Objective:To evaluate the role of autophagy in ischemia postconditioning (IPO)-induced attenuation of intestinal ischemia-reperfusion (I/R) injury in mice.Methods:Thirty-two SPF healthy adult male C57BL/6J mice, aged 9-12 weeks, weighing 25-29 g, were divided into 4 groups ( n=8 each) using a random number table method: sham operation group (group S), intestinal I/R group (group IIR), group IPO and IPO plus 3-methyladenine (3-MA) group (group IPO+ 3-MA). The model of intestinal I/R was established by occlusion of superior mesenteric artery for 45 min followed by 2-h reperfusion in anesthetized animals.The mice underwent 3 cycles of 30-s reperfusion followed by 30-s ischemia before restoration of reperfusion in group IPO.Blood samples from the femoral artery were collected at 2 h of reperfusion for determination of concentrations of serum diamine oxidase (DAO), D-lactate (D-LA) and intestinal fatty acid binding protein (I-FABP). The animals were then sacrificed and intestinal tissues were removed for microscopic examination of the pathologic changes which were scored according to Chiu and for determination of the expression of autophagy-related proteins Beclin-1 and p62 (by Western blot). The water content of intestinal tissues was calculated. Results:Compared with group S, the Chiu′s score, concentrations of serum DAO, D-LA and I-FABP, water content of intestinal tissues, and LC3Ⅱ/LC3Ⅰ ratio were significantly increased, Beclin-1 expression was up-regulated, and p62 expression was down-regulated in IIR, IPO and IPO+ 3-MA groups ( P<0.05). Compared with group IIR, the Chiu′s score, concentrations of serum DAO, D-LA and I-FABP, water content of intestinal tissues, and LC3Ⅱ/LC3Ⅰ ratio were significantly decreased, Beclin-1 expression was up-regulated, and p62 expression was down-regulated in group IPO ( P<0.05). Compared with group IPO, the Chiu′s score, concentrations of serum DAO, D-LA and I-FABP, and water content of intestinal tissues were significantly increased, LC3Ⅱ/LC3Ⅰratio was decreased, Beclin-1 expression was down-regulated, and p62 expression was up-regulated in group IPO+ 3-MA ( P<0.05). Conclusion:Autophagy is involved in ischemia postconditioning-induced attenuation of intestinal I/R injury in mice.