Objective To test the hypothesis that backward crawling and forward crawling share similar inter-joint coordination patterns,thus providing potential evidence for the application of backward crawling in rehabilitation training.Methods The acceleration signals in the X,Y,and Z directions for 9 joints(including bilateral wrists,elbows,shoulders,knees,and hips)in 9 volunteers during forward and backward crawling were collected using a custom signal acquisition system,and the pressure signals were also recorded when the palms contacted the ground.The collected acceleration signals were preprocessed,segmented into cycles,and vectorized.Based on the pressure signals,a single crawling cycle was divided into support phase and swing phase.In addition,principal component analysis was applied to extract inter-joint coordination in limbs at various scales(sagittal,coronal,and transverse planes).Pearson correlation coefficients of inter-joint coordination patterns were compared between forward and backward crawling in support period,swing period,and full cycle.Results The correlation coefficients for coordination patterns in the full cycle at the transverse plane scale were 0.813 5(PC1)and 0.837 5(PC2),and the correlation coefficient of the support period PC2 was 0.901 8.At the sagittal plane scale,the correlation coefficient of the support period PC1 was 0.948 5.Conclusion The study provides preliminary evidence that limb motion coordination patterns during backward crawling are similar to those observed during forward crawling.Future research will further explore the effects of backward crawling on functional rehabilitation in individuals with motor impairments.

Objective:To investigate the molecular mechanism of the 5-methylcytosine(m5C)reader Y-box binding protein 1(YBX1)in participating in the development and progression of colorectal cancer(CRC)by regulating the stability of the ferroptosis inhibitor membrane-spanning 4-domains subfamily A 15(MS4A15).Methods:Bioinformatics databases were used to investigate the mRNA and protein expression levels of YBX1 in CRC.RT-qPCR was used to measure the expression level of YBX1 in CRC cells.LC-MS was used to measure the level of m5C modification in CRC cells and nor-mal colorectal mucosal cells.CCK-8 assay was used to observe the effect of YBX1 on the proliferation of CRC cells,Transwell assay was used to observe its effect on the migration ability of CRC cells,and flow cytometry was sued to observe its effect on the apoptosis of CRC cells.Bioinformatics methods were used to identify the ferrop-tosis inhibitors that can interact with YBX1 and potential m5C modification sites.GEPIA2 was used to analyze the association between the expression of YBX1 and MS4A15.The expression of YBX1 was inhibited,and then the mRNA expression level and m5C modifica-tion level of MS4A15 were analyzed.The catRAPID database was used to find the binding sites between YBX1 protein and MS4A15 mRNA.CRC cells were treated with actinomycin D after inhibition of YBX1 expression,and RT-qPCR was used to measure the stabil-ity of MS4A15 mRNA.The expression of MS4A15 was inhibited,and then the proliferative activity,migration ability,and apoptosis rate of cells were measured,as well as the expression levels of the key indicators for ferroptosis,including MDA,ROS,and Fe2+.Results:High mRNA and protein expression levels of YBX1 were observed in CRC,and YBX1 was highly expressed in CRC cells.The m5C modification level of CRC cells was significantly higher than that of normal colorectal mucosal cells.YBX1 could promote the prolifera-tion and migration of CRC cells and inhibit the apoptosis of CRC cells.The bioinformatics analysis showed that YBX1 was positively correlated with the expression level of the ferroptosis inhibitor MS4A15,and there were multiple m5C modification sites on MS4A15.Inhibition of YBX1 expression could reduce the mRNA expression level and m5C modification level of MS4A15 and the stability of MS4A15 mRNA.There were significant reductions in the proliferative activity and migration ability of CRC cells and a significant in-crease in the apoptosis rate of CRC cells after inhibition of MS4A15 expression,with significant increases in the content of MDA,ROS,and Fe2+.Conclusion:These results show that YBX1 promotes the development and progression of CRC by stabilizing MS4A15 via m5C modification,which provides a promising targeted therapeutic strategy for CRC patients.

Objective·To analyze the influencing factors of left ventricular mass index(LVMI)in patients with essential hypertension,and explore the relationship between aldosterone levels and left ventricular hypertrophy(LVH).Methods·A total of 155 patients with essential hypertension,hospitalized in the Hypertension Department of the Northern Campus of Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,from January 2013 to December 2019,and excluded from primary aldosteronism by saline load test(post-saline suppression plasma aldosterone<60 pg/mL),were enrolled.General clinical data(age,gender,smoking status,duration of hypertension,etc.),physical examination data(blood pressure and body mass index),blood biochemistry(renal function,electrolytes,fasting blood glucose,and lipids),urinary sodium,and relevant hormones(basal and activated aldosterone,basal and activated renin,urinary aldosterone,post-saline suppression aldosterone,etc.)were collected.LVMI was evaluated by echocardiography.Pearson correlation analysis was used to assess the linear association between LVMI and each variable.Binary Logistic regression models were applied to screen independent risk factors for LVH.Multiple linear regression models were used to assess the impact of variables on LVMI.Results·The mean age of the 155 patients was(46.85±11.08)years,with 51.6%being male.Pearson correlation analysis showed that LVMI was significantly positively correlated with post-saline suppression aldosterone(r=0.334,P<0.001),age(r=0.184,P=0.032),duration of hypertension(r=0.241,P=0.005),systolic blood pressure(r=0.280,P=0.001),and pulse pressure(r=0.339,P<0.001).No significant correlations were found with diastolic blood pressure,body mass index,fasting blood glucose,total cholesterol,low-density lipoprotein cholesterol,triglyceride,high-density lipoprotein cholesterol,urinary sodium,basal aldosterone,activated aldosterone,or urinary aldosterone.After adjusting for confounders,including gender,smoking history,age,duration of hypertension,body mass index,pulse pressure,systolic blood pressure,fasting blood glucose,and total cholesterol,binary Logistic regression showed that each 1 pg/mL increase in post-saline suppression aldosterone was associated with a 5.1%increased risk of LVH(OR=1.051,95%CI 1.016?1.088,P=0.004).Multiple linear regression identified suppressed aldosterone(β=0.359,P<0.001),duration of hypertension(β=0.168,P=0.046),and pulse pressure(β=0.226,P=0.008)as independent influencing factors for LVMI.Conclusion·Suppressed aldosterone is an independent influencing factor for LVH in patients with essential hypertension.

Objective·To analyze the influencing factors of left ventricular mass index(LVMI)in patients with essential hypertension,and explore the relationship between aldosterone levels and left ventricular hypertrophy(LVH).Methods·A total of 155 patients with essential hypertension,hospitalized in the Hypertension Department of the Northern Campus of Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,from January 2013 to December 2019,and excluded from primary aldosteronism by saline load test(post-saline suppression plasma aldosterone<60 pg/mL),were enrolled.General clinical data(age,gender,smoking status,duration of hypertension,etc.),physical examination data(blood pressure and body mass index),blood biochemistry(renal function,electrolytes,fasting blood glucose,and lipids),urinary sodium,and relevant hormones(basal and activated aldosterone,basal and activated renin,urinary aldosterone,post-saline suppression aldosterone,etc.)were collected.LVMI was evaluated by echocardiography.Pearson correlation analysis was used to assess the linear association between LVMI and each variable.Binary Logistic regression models were applied to screen independent risk factors for LVH.Multiple linear regression models were used to assess the impact of variables on LVMI.Results·The mean age of the 155 patients was(46.85±11.08)years,with 51.6%being male.Pearson correlation analysis showed that LVMI was significantly positively correlated with post-saline suppression aldosterone(r=0.334,P<0.001),age(r=0.184,P=0.032),duration of hypertension(r=0.241,P=0.005),systolic blood pressure(r=0.280,P=0.001),and pulse pressure(r=0.339,P<0.001).No significant correlations were found with diastolic blood pressure,body mass index,fasting blood glucose,total cholesterol,low-density lipoprotein cholesterol,triglyceride,high-density lipoprotein cholesterol,urinary sodium,basal aldosterone,activated aldosterone,or urinary aldosterone.After adjusting for confounders,including gender,smoking history,age,duration of hypertension,body mass index,pulse pressure,systolic blood pressure,fasting blood glucose,and total cholesterol,binary Logistic regression showed that each 1 pg/mL increase in post-saline suppression aldosterone was associated with a 5.1%increased risk of LVH(OR=1.051,95%CI 1.016?1.088,P=0.004).Multiple linear regression identified suppressed aldosterone(β=0.359,P<0.001),duration of hypertension(β=0.168,P=0.046),and pulse pressure(β=0.226,P=0.008)as independent influencing factors for LVMI.Conclusion·Suppressed aldosterone is an independent influencing factor for LVH in patients with essential hypertension.

Objective To test the hypothesis that backward crawling and forward crawling share similar inter-joint coordination patterns,thus providing potential evidence for the application of backward crawling in rehabilitation training.Methods The acceleration signals in the X,Y,and Z directions for 9 joints(including bilateral wrists,elbows,shoulders,knees,and hips)in 9 volunteers during forward and backward crawling were collected using a custom signal acquisition system,and the pressure signals were also recorded when the palms contacted the ground.The collected acceleration signals were preprocessed,segmented into cycles,and vectorized.Based on the pressure signals,a single crawling cycle was divided into support phase and swing phase.In addition,principal component analysis was applied to extract inter-joint coordination in limbs at various scales(sagittal,coronal,and transverse planes).Pearson correlation coefficients of inter-joint coordination patterns were compared between forward and backward crawling in support period,swing period,and full cycle.Results The correlation coefficients for coordination patterns in the full cycle at the transverse plane scale were 0.813 5(PC1)and 0.837 5(PC2),and the correlation coefficient of the support period PC2 was 0.901 8.At the sagittal plane scale,the correlation coefficient of the support period PC1 was 0.948 5.Conclusion The study provides preliminary evidence that limb motion coordination patterns during backward crawling are similar to those observed during forward crawling.Future research will further explore the effects of backward crawling on functional rehabilitation in individuals with motor impairments.

BACKGROUND: Breast cancer patients who are positive for hormone receptor typically exhibit a favorable prognosis. It is controversial whether chemotherapy is necessary for them after surgery. Our study aimed to establish a multigene model to predict the relapse of hormone receptor-positive early-stage Chinese breast cancer after surgery and direct individualized application of chemotherapy in breast cancer patients after surgery. METHODS: In this study, differentially expressed genes (DEGs) were identified between relapse and nonrelapse breast cancer groups based on RNA sequencing. Gene set enrichment analysis (GSEA) was performed to identify potential relapse-relevant pathways. CIBERSORT and Microenvironment Cell Populations-counter algorithms were used to analyze immune infiltration. The least absolute shrinkage and selection operator (LASSO) regression, log-rank tests, and multiple Cox regression were performed to identify prognostic signatures. A predictive model was developed and validated based on Kaplan-Meier analysis, receiver operating characteristic curve (ROC). RESULTS: A total of 234 out of 487 patients were enrolled in this study, and 1588 DEGs were identified between the relapse and nonrelapse groups. GSEA results showed that immune-related pathways were enriched in the nonrelapse group, whereas cell cycle- and metabolism-relevant pathways were enriched in the relapse group. A predictive model was developed using three genes ( CKMT1B , SMR3B , and OR11M1P ) generated from the LASSO regression. The model stratified breast cancer patients into high- and low-risk subgroups with significantly different prognostic statuses, and our model was independent of other clinical factors. Time-dependent ROC showed high predictive performance of the model. CONCLUSIONS A multigene model was established from RNA-sequencing data to direct risk classification and predict relapse of hormone receptor-positive breast cancer in Chinese patients. Utilization of the model could provide individualized evaluation of chemotherapy after surgery for breast cancer patients.
Humans ; Female ; Breast Neoplasms/genetics* ; East Asian People ; Neoplasm Recurrence, Local/genetics* ; Breast ; Algorithms ; Chronic Disease ; Prognosis ; Tumor Microenvironment

Cadmium (Cd) is a common heavy metal in the environment. Cd²⁺ may penetrate the blood-brain barrier and produce neurotoxicity, thus inducing various neurodegenerative diseases. Celastrol is an effective component of Tripterygium wilfordii Hook. F., which has many pharmacological effects such as anti-cancer and anti-inflammatory. Here we explored the effect of celastrol on the corresponding neurotoxicity induced by Cd²⁺. Cell proliferation test, cell membrane integrity test, and cell morphology were observed to analyze the effect of Cd²⁺ on the viability of HMC3. The neurotoxicity of Cd²⁺ and the effect of celastrol on the corresponding neurotoxicity induced by Cd²⁺ were analyzed by nitric oxide (NO) test, lipid peroxidation (MDA) test, and Western blotting. When the concentration of Cd²⁺ reached 40 μmol/L, the inhibition rate of HMC3 cell proliferation was (57.17±8.23)% (P < 0.01, n=5), compared with the control group. The cell activity continued to reduce when the Cd²⁺ concentration further increased. When the concentration of Cd²⁺ was higher than 40 μmol/L, the cell membrane of HMC3 was significantly damaged, and the damage was dose-dependent. Upon increasing the Cd²⁺ concentration, the cell morphology began to change and the adhesion also became worse. Cd²⁺ significantly increased the amount of NO released by HMC3 cells, while celastrol effectively inhibited the NO release of HMC3 cells induced by Cd²⁺. Cd²⁺ greatly increased the release of MDA in HMC3 cells, and the level of MDA decreased rapidly upon the addition of 10^-7 mol/L celastrol. Cd²⁺ increased the expression of p-PI3K protein, and the levels of p-PI3K protein and p-AKT protein were inhibited by the addition of celastrol (10^‒7 mol/L, 10^‒6 mol/L), thus preventing cell apoptosis. In conclusion, celastrol inhibits Cd²⁺ induced microglial cytotoxicity and plays a neuroprotective role.
Anti-Inflammatory Agents/pharmacology* ; Apoptosis ; Cadmium/toxicity* ; Nitric Oxide/pharmacology* ; Pentacyclic Triterpenes ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt/metabolism* ; Triterpenes/pharmacology*

Objective:To determine mutations in the PTPN11 gene in a family with LEOPARD syndrome.Methods:Clinical evaluation was carried out in a large pedigree with confirmed LEOPARD syndrome diagnosed in Hwa Mei Hospital, University of Chinese Academy of Sciences. Peripheral blood samples were obtained from 4 patients and 2 unaffected healthy members in the family, as well as 100 unrelated healthy controls. DNA was extracted from the blood samples, and PCR was performed to amplify all exons of the PTPN11 genes, followed by Sanger sequencing.Results:There were 14 members in 3 generations of the family, 6 of whom were affected (3 males and 3 females) , demonstrating an autosomal dominant inheritance pattern. Skin lesions were mainly distributed on the face, trunk and limbs, accompanied by special facial features and cardiovascular system abnormalities. A missense mutation c.1632G>T (p.R558L) in the PTPN11 gene was identified in the 4 patients, which resulted in the substitution of arginine by leucine at amino acid position 558. This mutation had not yet been reported previously. No mutation was detected in the PTPN11 gene in the 2 unaffected family members or 100 healthy controls.Conclusion:The missense mutation c.1632G>T in exon 13 of the PTPN11 gene may be the molecular basis for LEOPARD syndrome in this family.

To enhance recombinant protein production by CHO cells, We compared the impact of overexpression of metabolic enzymes, namely pyruvate carboxylase 2 (PYC2), malate dehydrogenase Ⅱ (MDH2), alanine aminotransferase Ⅰ (ALT1), ornithine transcarbamylase (OTC), carbamoyl phosphate synthetase Ⅰ (CPSⅠ), and metabolism related proteins, namely taurine transporter (TAUT) and Vitreoscilla hemoglobin (VHb), on transient expression of anti-hLAG3 by ExpiCHO-S. Overexpression of these 7 proteins could differentially enhance antibody production. OTC, CPSI, MDH2, and PYC2 overexpression could improve antibody titer by 29.2%, 27.6%, 24.1%, and 20.3%, respectively. Specifically, OTC and MDH2 could obviously improve early-stage antibody production rate and the culture period was shortened by 4 days compared with that of the control. In addition, OTC and MDH2 had little impact on the affinity of anti-hLAG3. In most cases, overexpression of these proteins had little impact on the cell growth of ExpiCHO-S. MDH2 and ALT1 overexpression in H293T cells could also improve antibody production. Overall, overexpression of enzymes involved in cellular metabolism is an effective tool to improve antibody production in transient expression system.
Animals ; CHO Cells ; Cricetinae ; Cricetulus ; Enzymes/metabolism* ; Recombinant Proteins/genetics*

Objective: To investigate the clinicopathological characteristics, treatment and prognosis of head and neck carcinosarcoma. Methods: The clinical data of 14 patients with head and neck carcinosarcoma treated in the First Affiliated Hospital of Zhengzhou University from January 2010 to May 2020 were retrospectively analyzed, including 11 males and 3 females, with age range from 30 to 72 years old. Clinicopathological characteristics, treatments and follow-up results of patients were evaluated. Kaplan-Meier method was used to estimate the cumulative survival rate. Results: Histopathological examination showed the co-existence of malignant epithelial and mesenchymal components in all cases. Immunohistochemical staining of 13 cases showed cytokeratin and epithelial membrane antigens were positively expressed in the epithelial areas, whereas vimentin was positive in the malignant mesenchymal tissue area. Among 14 cases, 5 cases were treated with surgery, 3 cases with surgery and radiotherapy, and 6 cases with surgery, radiotherapy and chemotherapy. The follow-up time was 2-81 months, with a median follow-up time of 22.5 months. Except for one patient who was lost to follow-up in 21 months after treatment, among the remaining 13 patients, 4 patients had recurrence, 8 patients died, and 5 patients had a tumor-free survival. The Kaplan-Meier analysis showed that the 1, 3, and 5-year cumulative survival rates of 14 patients with head and neck carcinosarcoma were 64.3%, 57.1%, and 42.9%, respectively. Conclusions: Carcinosarcoma of the head and neck is rare in clinic, histopathological and immunohistochemical examinations are important basis for diagnosis, and surgery is a preferred treatment. Carcinosarcoma of the head and neck has a poor prognosis, and patients should be followed up for a long time.
Adult ; Aged ; Carcinosarcoma/therapy* ; Female ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Prognosis ; Retrospective Studies