Effect of aerosol inhalation of budesonide on respiratory symptoms and inflammatory factors in patients with asthma: a meta-analysis.

OBJECTIVE: To review the efficacy, symptoms, inflammatory factors and pulmonary function of different doses of budesonide aerosol inhalation in the treatment of patients with asthma. METHODS: The Chinese and English literature databases were searched with "Effects of different doses of budesonide aerosol inhalation on the efficacy, lung function, inflammation, symptoms and adverse reactions in patients with asthma" as the search direction, and a Meta-analysis was performed. RESULTS: Compared with the low dose group, the efficacy, PEF and FEV1 were significantly increased and the clinical symptom score, TNF-α and IL-4 were significantly decreased in the high dose group (p < 0.05). There was no significant difference in IFN-γ level and the incidence of adverse reactions between the two groups (p > 0.05). CONCLUSION: High-dose budesonide aerosol inhalation therapy can improve the efficacy and lung function of patients, reduce inflammation and clinical symptoms, and does not increase the risk of adverse reactions, which is worthy of clinical promotion.

A clinical study of non-bioartificial liver DPMAES support system in hepatitis B-related acute-on-chronic liver failure.

This study aims to observe the clinical efficacy of the dual plasma molecular adsorption exchange system (DPMAES) in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF), with a focus on its regulatory effect on cytokine storm. A total of 60 HBV-ACLF patients were enrolled in this study. The observation group, comprising 30 patients, received DPMAES treatment, while the control group underwent PE treatment. We compared the efficacy changes between the two groups post-treatment. A total of 55 HBV-ACLF patients who completed the study were analyzed, Patients treated with DPMAES showed significant improvements in clinical outcomes. After DPMAES treatment, HBV-ACLF patients exhibited notably 90 day survival rate increased by 18% compared to those in the PE group. Moreover, total bilirubin levels decreased markedly, albumin and platelet levels increased compared to the PE group. After DPMAES treatment, the patient showed a significant decrease in inflammatory cytokine IL-6 (t = 5.046, P < 0.001) and a significant decrease in procalcitonin (t = 4.66, P < 0.001). DPMAES was more effective than PE in rapidly reducing TBiL, improving coagulation function and mitigating cytokine storm. It maintained platelet stability more effectively while minimizing albumin consumption to a greater extent, significantly improved 90-day survival.Trial registration: Chinese Clinical Trial Registry, ChiCTR2300076117.

Effect of different fusion devices on cervical sagittal parameters after anterior cervical discectomy and fusion for cervical spondylotic myelopathy / 中国组织工程研究

BACKGROUND:The impact of anterior cervical surgery on the sagittal balance parameters of the cervical spine is gradually being paid attention to.Currently,there is a lack of clear and feasible clinical guidelines for the selection of surgical methods for two-level cervical spondylosis,aiming to find the most suitable fixation method that is more beneficial for this type of patient. OBJECTIVE:To compare the effects of different fusion devices for anterior cervical decompression on the changes of cervical sagittal parameters after surgery for adjacent two-level cervical spondylotic myelopathy. METHODS:A total of 44 patients with adjacent two-level cervical spondylotic myelopathy underwent anterior cervical discectomy and fusion from March 2018 to September 2020 in Liaocheng People's Hospital were retrospectively analyzed in the study,and they were divided into zero-p group(23 cases)and cage group(21 cases).All patients underwent anteroposterior X-ray,three-dimensional CT reconstruction and MRI examination before operation.At the last follow-up,the anteroposterior X-ray films of cervical spine were taken.The sagittal balance parameters of the cervical spine were measured before and after surgery,including cervical lordotic angle(C2-7 Cobb),C2-C7 sagittal vertical axis,segmented lordotic angle and T1 slope.The surgical time,intraoperative bleeding,last follow-up intervertebral fusion,and postoperative swallowing disorders were recorded,and Japanese Orthopaedic Association score on the patient was evaluated before and after surgery.The changes in cervical sagittal parameters before and after surgery were calculated and their differences were compared between the two groups. RESULTS AND CONCLUSION:(1)Both groups of patients successfully completed the surgery and received follow-up.The zero-p group had shorter surgical time and less intraoperative bleeding compared to the cage group,but the difference was not statistically significant(P>0.05).(2)The incidence rate of postoperative swallowing disorders in the cage group(7/21,33%)was higher than that in the zero-p group(3/23,13%),and the difference was statistically significant(P<0.05).(3)At the last follow-up,the clinical efficacy of the two groups was the same;all patients had bone fusion.Comparison within the group showed that the sagittal parameters of the cervical spine in both groups improved compared to before surgery(P<0.05).There was no statistically significant difference in sagittal parameters between groups(P>0.05),and there was no statistically significant difference in changes in C2-C7 sagittal vertical axis,C2-7 Cobb angle,and T1 slope between the two groups(P>0.05).However,the segmented lordotic angle changes in the zero-p group were smaller than those in the cage group,and the difference was statistically significant(P<0.05).(4)It is indicated that the use of zero-p and titanium plate combined with cage during anterior cervical discectomy and fusion surgery can effectively improve cervical sagittal balance.Titanium plate combined with cage intervertebral fusion can better reconstruct the patient's cervical lordosis and curvature.The selection of fusion devices should also comprehensively consider the occurrence of surgical complications.

Clinical Characteristics and Use of Traditional Chinese Medicine Therapy in 222 Malignant Tumor Cases with COVID-19： A Retrospective Study / 中医杂志

ObjectiveTo analyze the clinical characteristics and the use of traditional Chinese medicine （TCM） therapy in cancer patients with COVID-19， and to provide reference for making TCM prevention and treatment strategies and determining diagnosis and treatment priorities for patients with malignant tumors in the COVID-19 epidemic. MethodsThe medical records of 225 malignant tumor cases with COVID-19 who were admitted to 7 national research centers from January 1st to 20th， 2023 were retrospectively collected， and the main symptoms and duration after infection， nucleic acid negative conversion time， use of TCM therapy， and changes in adverse reactions after resuming anti-tumor treatment were analyzed. ResultsA total of 222 malignant tumor patients with COVID-19 were included in the analysis， involving 205 mild cases and 17 moderate cases. The top four most frequently reported clinical symptoms were fever （165 cases）， expectoration or dry cough （99 cases）， decreased appetite （95 cases） and fatigue （85 cases）， of which 40 expectoration or dry cough cases ， 37 fatigue cases and 29 decreased appetite cases lasted for more than 14 days. One hundred and five patients with nucleic acid detection report had a median negative conversion time of 14 days. The nucleic acid negative conversion time was significantly longer in patients with lung cancer compared to those with digestive system malignant tumors， and in those with myelosuppression than those without （P＜0.01）. During the infection period， 47.30% （105/222） of the patients used Chinese patent medicine， and 21.17% （47/222） were treated with herbal decoctions. The use of TCM in patients during the prevention and rehabilitation period， was 1.80%（4/222） and 7.21%（16/222）， respectively. Fifty-five patients resumed anti-tumor treatment after nucleic acid negative conversion， and received TCM simultaneously. Observed adverse reactions， including gastrointestinal reactions， bone marrow suppression， and neurotoxicity， were all grade 1 to 2， and no new adverse events occurred during follow-up. ConclusionCertain malignant tumor patients with COVID-19 had prolonged symptoms and nucleic acid negative conversion time Rational use of TCM can help to promote the rehabilitation of the patients and ensure the smooth process of anti-tumor treatment after infection.

Evaluation of Clinical Efficacy of Modified Houpo Dahuangtang in Moderate and Severe ARDS Patients Based on Electrical Impedance Tomography / 中国实验方剂学杂志

ObjectiveTo evaluate the clinical efficacy of modified Houpo Dahuangtang in moderate and severe acute respiratory distress syndrome （ARDS） patients with phlegm-heat accumulation，and monitor the pulmonary ventilation changes of patients before and after treatment by electrical impedance tomography（EIT）. MethodThe 62 cases of moderate and severe ARDS patients with phlegm-heat accumulation who required mechanical ventilation in the department of intensive care unit （ICU） in Chongqing Hospital of Traditional Chinese Medicine from September 2021 to June 2022 were selected，and divided into an experimental group（31 cases）and a control group（31 cases）using a random number table. On the basis of regular Western medicine treatment，the experimental group received modified Houpo Dahuangtang and the control group received warm water by a nasogastric tube for seven days. The changes in the clinical efficacy of traditional Chinese medicine（TCM），the oxygenation index［arterial oxygen partial pressure （PaO2）/fractional inspired oxygen（FiO2），P/F］，lactic acid（Lac），acute physiology and chronic health evaluation Ⅱ（APACHE Ⅱ） score，compliance，plateau pressure，gas distribution parameters monitored by EIT（Z1，Z2，Z3 and Z4），inflammatory factors［interleukin-6 （IL-6），IL-10， tumor necrosis factor-α （TNF-α） and C-reactive protein （CRP）］ of both groups before and after treatment were recorded. Besides， the mechanical ventilation time， length of stay in ICU， 28-day mortality and incidence of adverse reactions（delirium，abdominal pain and diarrhea）in the two groups were also observed. ResultThere was no significant difference in the baseline indexes of patients in the two groups，and thus the two groups were comparable. After treatment for one week， the total effective rate for TCM syndromes in the experimental group was 90.30%（28/31）， higher than the 67.74%（21/31）in the control group（Z=-2.415，P<0.05）.Compared with the same group before treatment， the plateau pressure and Lac decreased （P<0.01）and the compliance and P/F increased （P<0.01） in experimental group， while the Lac decreased （P<0.05）and the P/F increased （P<0.05）， and the compliance and plateau pressure did not change significantly in the control group. After treatment，the plateau pressure and inflammatory factors in the experimental group were lower than those in the control group（P<0.05）， but the compliance and P/F in the experimental group were higher than those in the control group（P<0.05）， and the gas distribution parameters Z1，Z2，Z3，Z4，Z1+Z2，and Z3+Z4 monitored by EIT in the experimental group were all higher than those in the control group （P<0.05）. There was no significant difference in mechanical ventilation time， ICU hospitalization time， 28-day mortality， delirium， abdominal pain， diarrhea and other adverse reactions between the two groups. ConclusionModified Houpo Dahuangtang can significantly improve the P/F，pulmonary ventilation in gravity-dependent regions and pulmonary compliance，reduce the release of inflammatory factors in moderate and severe ARDS patients. Compared with conventional methods，EIT can timely monitor the pulmonary ventilation changes in ARDS patients，which suggests its clinical feasibility.

Association of attention deficit hyperactivity disorder symptoms and bullying behavior in children / 中国学校卫生

Objective@#The association between school bullying and attention deficit hyperactivity disorder (ADHD) symptoms among students in primary schools and the moderating role of gender was explored to provide scientific evidence for the prevention and control of school bullying.@*Methods@#A total of 4 764 students from 2 primary schools in Wuhan were selected using the convenience sampling method in March 2023. The Olweus Bully/Victim Questionnaire and Strengths and Difficulties Questionnaire were used. A Pearson χ 2 test was used to compare differences in school bullying rates among children with and without ADHD symptoms. Pearson correlation analysis and Process 3.3 were used to analyse the association between ADHD symptoms, and school bullying behaviour and the moderating role of gender.@*Results@#The reported rate of bullying victims in primary schools was 24.2% and the rate of bullying perpetration was 3.8%. The rate of ADHD symptom detection among primary school students was 5.9%. ADHD symptoms were positively associated with bullying and bullying victim behaviour ( r =0.16, 0.27, P <0.01). Specifically, the association between ADHD symptoms and bullying behavior tended to be stronger among boys than girls ( β boy =0.17, t =11.13; β girl =0.07, t =4.11, P <0.01).@*Conclusions@#ADHD symptoms are an important factor influencing school bullying behaviors in students, and gender moderates the association. In the process of preventing and controlling school bullying, ADHD symptoms and gender differences should be emphasized and comprehensive interventions should be implemented.

Effect of progressive resistance exercise using Thera-band on edema volume, upper limb function, and quality of life in patients with breast cancer-related lymphedema.

This study aimed to determine the effects of progressive resistive exercise (PRE), including complex decongestive physical therapy (CDPT), on edema volume, handgrip strength, upper extremity function, and quality of life (QoL) in patients with breast cancer-related lymphedema (BCRL). Twenty patients were randomized between the progressive resistance exercise group (PREG) and the self-home resistance exercise group (SREG). Two patients in each group dropped out of the study, leaving 16 patients: n=8 in the exercise group and n=8 in the SREG. First, the PREG and the SREG received CDPT. Subsequently, the patients in the PREG performed PRE, whereas the patients in the SREG performed self-home resistance exercises. Interventions were performed for 50 min, 3 times a week, for 6 weeks. The results showed that, for the edema volume, a significant intergroup variation was absent, whereas the intragroup variation was significant. The inter- and intragroup variations were significant for both handgrip strength and upper extremity function. Regarding QoL, a significant difference was observed in global health status/QoL and role function between the groups. Furthermore, significant differences were observed within the PREG in global health status/QoL; physical, role, and cognitive function; and dyspnea. No significant differences were observed within the SREG. The results collectively suggest that the exercise program was an intervention with a greater potential contribution to reducing edema and enhancing physical function in patients with BCRL.

Research progress of diabetic renal fibrosis / 中国药理学通报

Diabetic nephropathy (DN) is one of the most common and serious microvascular complications in patients with diabetes mellitus. Diabetic renal fibrosis ( DRF) is a major pathological change in the development of DN. In recent years the incidence of renal fibrosis (RF) has remained high. For diabetic patients, RF may expose them to kidney transplantation or even death, which brings a great burden to themselves and their families. Therefore, learning the pathogenesis and the current treat ment status of DRF is crucial for the treatment of the disease and the development of new drugs. Here we review the general situa¬tion of DN, the general situation, molecular mechanism, and the treatment of DRF,looking forward to providing a reference for the research and treatment of DRF.

Analysis of the pathogenesis and risk factors of gallstone / 中华外科杂志

Objective: To explore the pathogenesis and risk factors of gallstone formation. Methods: The findings of hepatobiliary ultrasound and related data were collected from healthy subjects who underwent a physical examination at Xuanwu Hospital of Capital Medical University from January 2012 to December 2021. A total of 98 344 healthy subjects were included in the study,including 48 241 males and 50 103 females,with a ratio of 1∶1.03,aged (42.0±15.6)years(range:14 to 97 years). The gender,age,body mass index,waist circumference,systolic pressure,diastolic pressure,ALT,AST,total bilirubin,fasting blood glucose,triglyceride,total cholesterol,low-density lipoprotein,high-density lipoprotein were collected.Healthy subjects were required to sit for at least 10 minutes before blood pressure was measured.Rresults of fasting venous blood were collected after 8 to 12 hours on an empty stomach.According to the presence of gallstones by ultrasound results, healthy subjects were divided into study group and control group. Data were analyzed by rank-sum tests and χ2 test, and risk factors for gallstone formation were explored by Logistic regression analysis. Results: The incidence of gallstones in this group was 5.42%(5 333/98 344). Among them,the incidence of gallstones in people aged 60 years and above was significantly higher than that in people under 60 years old(15.31%(2 348/15 334) vs. 3.60%(2 985/83 010), χ2=3 473.46,P<0.05).The healthy subjects were divided by age for every 10 years,and the results showed that the incidence of gallstones increased with age. The incidence of gallstones in females was 5.68%(2 844/50 103),greater than 5.16%(2 489/48 241) in males(χ2=11.81,P<0.05). Among them,1 478 cases underwent gallbladder surgical resection due to gallstones,and the operation rate was 27.71%. The operation rate reached the peak between 60 and <70 years old,and decreased after 70 years old. The results of the multivariate analysis showed that,female(OR=1.38, P<0.01),age(OR=1.58, P<0.01),body mass index≥24 kg/m2(OR=1.31, P<0.01),waist circumference≥85 cm(OR=1.24, P<0.01),fasting blood glucose>6.1 mmol/L(OR=1.18,P<0.01),total cholesterol≥5.18 mmol/L(OR=0.87, P=0.019),low-density lipoprotein≥3.37 mmol/L(OR=1.15,P=0.001) were the risk factors for gallstone formation;high-density lipoprotein≥1.55 mmol/L(OR=0.87, P<0.01) was a protective factor for gallstone formation. Conclusions: The incidence of gallstones increases with age in male and female. Gender,age,body mass index,waist circumferenc,fasting blood glucose,total cholesterol,LDL,and HDL are related factors with gallstone formation.

The Relationship between Occurrence of aGVHD in Patients with Acute Myeloid Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation and Immune Cell Components in Graft / 中国实验血液学杂志

OBJECTIVE@#To explore the relationship between occurrence of acute graft-versus-host disease (aGVHD) and various immune cell composition in patients with acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*METHODS@#The clinical data of 104 patients with AML undergoing allo-HSCT in our hospital were retrospectively analyzed, and the hematopoietic reconstitution and occurrence of GVHD were analyzed. Flow cytometry was used to detect the proportion of various types of immune cells in the grafts, the number of graft composition in patients with different degrees of aGVHD was calculated and compared, and to analyze the correlation between the severity of aGVHD in AML patients after allo-HSCT and the immune cell components in the graft.@*RESULTS@#There was no significant difference in the time of hematopoietic reconstitution between the high number group of total number of nucleated cells (TNC) and the low number group, while the time of neutrophil and platelet reconstruction in the high number of CD34 group was significantly faster than that in the low number of CD34 group (P＜0.05), and the total hospital stay also tends to be shorten. Compared with patients in 0-Ι aGVHD group, both HLA-matched and HLA-haploidentical transplantation, the infusion amounts of CD3+ cells, CD3+CD4+ cells, CD3+CD8+ cells, NK cells and CD14+ monocytes were higher in patients of Ⅱ-Ⅳ aGVHD group， but the difference was not statistically significant (P>0.05); In addition, in patients with HLA-haploidentical transplantation, the number of CD4+CD25+ cells in Ⅱ-Ⅳ aGVHD group was significantly lower than that in 0-Ι aGVHD group (P<0.05), and the same trend was also observed in HLA-matched transplanted patients, but the difference was not significant (P=0.078).@*CONCLUSION@#High number of CD34+ cells in the graft is beneficial to hematopoietic reconstitution in AML patients. To a certain degree, high number of CD3+ cells, CD3+CD4+ cells, CD3+CD8+ cells, NK cells and CD14+ cells tend to increase the occurrence of aGVHD, but high number of CD4+CD25+ regulatory T cells is beneficial to reduce the incidence of aGVHD in AML patients.

Clinical characteristics of a SPONASTRIME-type spondyloepimetaphyseal dysplasia family and analysis of TONSL gene mutation / 中华内分泌代谢杂志

Objective:To provide molecular evidence for clinical diagnosis and genetic counseling by analyzing the clinical characteristics and identifying the pathogenic genes in a SPONASTRIME-type spondyloepimetaphyseal dysplasia(SEMDSP)family.Methods:Clinical data of the family members was collected and analyzed. Case 2 was identified as the proband for whole-exome sequencing and variant analysis. Suspected variants were validated across family numbers using Sanger sequencing.Results:The two affected individuals in this family, a brother and a sister, both presented as short stature. The initial diagnosis for the sister(case 1)was made at the age of 4 years and 2 months(height: 88.6 cm), and for the brother(case 2)at 4 years and 4 months(height: 81.6 cm). Both individuals exhibited distinctive facial features, including frontal bossing, midface hypoplasia with depressed nasal bridge, upturned nostrils, ocular hypertelorism, and epicanthus, thick hair, short lingual frenulum, stubby fingers and palms, and absence of scoliosis. The parents displayed normal phenotypes. Laboratory tests indicated growth hormone deficiency in both affected individuals. Imaging studies revealed significant bone age delay in case 2, while case 1 showed longitudinal striations at the distal radius but with bone age matching their actual age(5 years and 11 months). Despite receiving recombinant human growth hormone treatment, both patients had inadequate responses. Genetic testing identified compound heterozygous mutations in the TONSL gene shared by the two siblings. These mutations included a paternally inherited c. 1291-14_1291-11delCCTC and a maternally inherited c. 1909_1920delACGCTGCAGCAG. Notably, SEMDSP families have not been reported in China, and the c. 1909_1920delACGCTGCAGCAG mutation is a novel variant.Conclusion:Two patients were diagnosed as spondyloepimetaphyseal dysplasia, SPONASTRIME type, and the compound heterozygous variant was the genetic cause of this family.

Clinical and genetic analysis of a patient with primary distal renal tubular acidosis due to variants of ATP6V0A4 gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical features and genetic etiology of a patient with primary distal renal tubular acidosis (dRTA).@*METHODS@#A child who was diagnosed with primary dRTA at the Xi'an Children's Hospital in April 2021 due to poor appetite and persistent crying was selected as the study subject. Clinical data of the patient was collected. Whole exome sequencing (WES) was carried out for the child. Candidate variants were validated by Sanger sequencing of his family members.@*RESULTS@#The child, a 1-month-and-18-day male, had featured poor appetite, persistent crying, poor weight gain and dehydration. Laboratory examination has suggested metabolic acidosis, hyperchloremia, hypokalemia, abnormal alkaline urine and anemia. Ultrasonographic examination of the urinary system revealed calcium deposition in renal medulla. DNA sequencing revealed that he has harbored compound heterozygous variants of the ATP6V0A4 gene, namely c.1363dupA (p.M455NfsX14) and c.2257C>T (p.Q753X), which were respectively inherited from his father and mother. Based on the guidelines from the American College of Medical Genetics and Genomics, both variants were classified as pathogenic (PVS1+PM3+PM2_Supporting).@*CONCLUSION@#The compound heterozygous variants of c.1363dupA (p.M455NfsX14) and c.2257C>T (p.Q753X) of the ATP6V0A4 gene probably underlay the pathogenesis of primary dRTA in this patient. Discovery of the c.2257C>T (p.Q753X) variant has also expanded the mutational spectrum of the ATP6V0A4 gene.

Clinical and genetic analysis of an infant with permanent neonatal diabetes mellitus due to novel variant of insulin gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for an infant with permanent neonatal diabetes mellitus (PNDM).@*METHODS@#Clinical data of the child was collected. Targeted capture-next generation sequencing was carried out to identify the potential variants. Candidate variant was verified by Sanger sequencing of her family members.@*RESULTS@#The child was a 4-month-and-26-day female featuring onset of ketoacidosis accompanied with fasting blood glucose of 24.4 mmol/L, positive urine glucose, decreased serum C-peptide, HbA1c of 9.58%, and negative diabetes autoantibody. Genetic testing revealed that she has carried a heterozygous c.314T>G (p.L105R) variant of the INS gene. Sanger sequencing verified that neither of her parents has carried the same variant, which was also unreported in the literature. The variant was classified as likely pathogenic based on the ACMG guidelines.@*CONCLUSION@#The c.314T>G (P.L105R) variant of the INS gene probably underlay the genetic etiology in this child. Genetic testing should be conducted for children with suspected PNDM for early diagnosis and appropriate treatment.

Clinical Study on the Relationship between Gene Mutation Profile and Prognosis in Pediatric Acute Lymphocyte Leukemia / 中国实验血液学杂志

OBJECTIVE@#To analyze the gene mutation profile in children with acute lymphocyte leukemia (ALL) and to explore its prognostic significance.@*METHODS@#Clinical data of 249 primary pediatric ALL patients diagnosed and treated in the Department of Hematological Oncology of Wuhan Children's Hospital from January 2018 to December 2021 were analyzed retrospectively. Next-generation sequencing (NGS) was used to obtain gene mutation data and analyze the correlation between it and the prognosis of children with ALL.@*RESULTS@#227 (91.2%) were B-ALL, 22 (8.8%) were T-ALL among the 249 cases, and 178 (71.5%) were found to have gene mutations, of which 85 (34.1%) had ≥3 gene mutations. NRAS(23.7%), KRAS (22.9%),FLT3(11.2%), PTPN11(8.8%), CREBBP (7.2%), NOTCH1(6.4%) were the most frequently mutated genes, the mutations of KRAS, FLT3, PTPN11, CREBBP were mainly found in B-ALL, the mutations of NOTCH1 and FBXW7 were mainly found in T-ALL. The gene mutation incidence of T-ALL was significantly higher than that of B-ALL (χ2= 5.573，P＜0.05) and were more likely to have co-mutations (P＜0.05). The predicted 4-year EFS rate (47.9% vs 88.5%, P＜0.001) and OS rate (53.8% vs 94.1%, P＜0.001) in children with tp53 mutations were significantly lower than those of patients without tp53 mutations. Patients with NOTCH1 mutations had higher initial white blood cell count （128.64×109/L vs 8.23×109/L，P＜0.001）, and children with NOTCH1 mutations had a lower 4-year EFS rate than those of without mutations (71.5% vs 87.2%, P＝0.037).@*CONCLUSION@#Genetic mutations are prevalent in childhood ALL and mutations in tp53 and NOTCH1 are strong predictors of adverse outcomes in childhood ALL, with NGS contributing to the discovery of genetic mutations and timely adjustment of treatment regimens.

Protein Kinase CK2 Modulates the Calcium Sensitivity of Type 3 Small-conductance Calcium-activated Potassium Channels in Colonic Platelet-derived Growth Factor Receptor Alpha-positive Cells From Streptozotocin-induced Diabetic Mice

Background/Aims@#The gastrointestinal symptom of diabetes mellitus, chronic constipation, seriously affects patients’ life. Whereas, the mechanism of chronic constipation is still ambiguous, resulting in a lack of effective therapies for this symptom. As a part of the smooth muscle cells, interstitial cells of Cajal, and platelet-derived growth factor receptor alpha-positive (PDGFRα+ ) cells syncytium (SIP syncytium), PDGFRα+ cells play an important role in regulating colonic motility. According to our previous study, in PDGFRα+cells in colons of diabetic mice, the function of the P2Y1 purinergic receptor/type 3 small-conductance calcium-activated potassium (SK3) channel signaling pathway is strengthened, which may lead to colonic dysmotility. The purpose of this study is to investigate the changes in SK3 channel properties of PDGFRα+ cells in diabetic mice. @*Methods@#Whole-cell patch clamp, Western blotting, superoxide dismutase activity measurement, and malondialdehyde measurement were main methods in the present study. @*Results@#The present study revealed that when dialysed with low calcium ion (Ca 2+ ) solution, the SK3 current density was significantly decreased in PDGFRα+ cells from diabetic mice. However, the SK3 current density in PDGFRα+ cells was enhanced from diabetic mice when dialysed with high Ca 2+ solution. Moreover, hydrogen peroxide-treatment mimicked this phenomenon in SK3 transgenic HEK293 cells. The subunit of SK3 channels, protein kinase CK2, was up-regulated in colonic muscle layers and hydrogen peroxidetreated HEK293 cells. Additionally, protein phosphatase 2A, the subunit of SK3 channels, was not changed in streptozotocin-treated mouse colons or hydrogen peroxide-treated HEK293 cells. @*Conclusion@#The diabetic oxidative stress-induced upregulation of CK2 contributed to modulating SK3 channel sensitivity to Ca 2+ in colonic PDGFRα+ cells, which may result in colonic dysmotility in diabetic mice.

Comprehensive characterisation of immunogenic cell death in melanoma revealing the association with prognosis and tumor immune microenvironment.

Increasing evidence has highlighted the critical functions of immunogenic cell death (ICD) within many tumors. However, the therapeutic possibilities and mechanism of utilizing ICD in melanoma are still not well investigated. Melanoma samples involved in our study were acquired from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. First, pan-cancer analysis of ICD systematically revealed its expression characteristics, prognostic values, mutation information, methylation level, pathway regulation relationship in multiple human cancers. The non-negative matrix factorization clustering was utilized to separate the TCGA-melanoma samples into two subtypes (i.e. C1 and C2) with different prognosis and immune microenvironment based on the expression traits of ICD. Then, LASSO-Cox regression analysis was utilized to determine an ICD-dependent risk signature (ICDRS) based on the differentially expressed genes (DEGs) between the two subtypes. Principal component analysis and t-distributed stochastic neighbor embedding analysis of ICDRS showed that high- and low-risk subpopulations could be clearly distinguished. Survival analysis and ROC curves in the training, internal validation, and external validation cohorts highlighted the accurate prognosis evaluation of ICDRS. The obvious discrepancies of immune microenvironment between the different risk populations might be responsible for the different prognoses of patients with melanoma. These findings revealed the close association of ICD with prognosis and tumor immune microenvironment. More importantly, ICDRS-based immunotherapy response and targeted drug prediction might be beneficial to different risk subpopulations of patients with melanoma. The innotative ICDRS could function as a marker to determine the prognosis and tumor immune microenvironment in melanoma. This will aid in patient classification for individualized melanoma treatment.

Integration of single-cell RNA sequencing and bulk RNA sequencing to reveal an immunogenic cell death-related 5-gene panel as a prognostic model for osteosarcoma.

Background: Despite the comparatively low prevalence of osteosarcoma (OS) compared to other cancer types, metastatic OS has a poor overall survival rate of fewer than 30%. Accumulating data has shown the crucial functions of immunogenic cell death (ICD) in various cancers; nevertheless, the relationship between ICD and OS was not previously well understood. This research aims to determine the function of ICD in OS and construct an ICD-based prognostic panel. Methods: Single cell RNA sequencing data from GSE162454 dataset distinguished malignant cells from normal cells in OS. The discrepancy in ICD scores and corresponding gene expression was intensively explored between malignant cells and normal cells. Using the RNA sequencing data of the TARGET-OS, GSE16091, GSE21257, and GSE39058 datasets, the molecular subtype of OS was determined by clustering seventeen ICD-related genes obtained from the literature. Differentially expressed genes (DEGs) between different molecular subtypes were identified to develop a novel ICD-associated prognostic panel. Results: The malignant cells had a remarkable decrease in the ICD scores and corresponding gene expression compared with normal cells. A total of 212 OS patients were successfully stratified into two subtypes: C1 and C2. C1-like OS patients were characterized by better prognostic outcomes, overexpression of ICD genes, activation of the ICD pathway, high inflitration abundance of immunocytes, and low expression levels of immune checkpoint genes (ICGs); however, the reverse is true in C2-like OS patients. Utilizing the limma programme in R, the DEGs between two subtypes were determined, and a 5-gene risk panel consisting of BAMBI, TMCC2, NOX4, DKK1, and CBS was developed through LASSO-Cox regression analysis. The internal- and external-verification cohorts were employed to verify the efficacy and precision of the risk panel. The AUC values of ROC curves indicated excellent prognostic prediction values of our risk panel. Conclusions: Overall, ICD represented a protective factor against OS, and our 5-gene risk panel serving as a biomarker could effectively evaluate the prognostic risk in patients with OS.

Ai-Tong-An-Gao-Ji and Fisetin Inhibit Tumor Cell Growth in Rat CIBP Models by Inhibiting the AKT/HIF-1α Signaling Pathway.

BACKGROUND: Ai-Tong-An-Gao-Ji (ATAGJ) has been extensively applied for acute bone cancer pain treatment with a satisfactory efficacy, while the specific mechanisms remain unclear and require further investigation. METHODS: Overlapped genes of ATAGJ and CIBP obtained from SwissTargetPrediction website and GeneCards database were presented as a Venn diagram. A network diagram of drug-component-target was further established using the Cytoscape 3.6.0 software. The effect of fisetin on Walker 256 cell proliferation was observed by clone formation assay and EDU assay, and the interaction between fisetin and AKT was revealed using the immunoprecipitation assay. Effects of fisetin on AKT/HIF-1α signaling pathway in Walker 256 cells were ultimately detected using Western blot and qPCR assays. RESULTS: The key component fisetin and core target gene AKT were sorted out using the drug-component-target network with a binding energy between fisetin and AKT less than -5 kcal/mol. Clone formation assay and EDU assay showed that fisetin substantially suppressed the proliferation of Walker 256 cells. Immunoprecipitation assay results revealed that the combination of fisetin and AKT decreased the level of AKT/HIF-1α signaling pathway of Walker 256 cells. CONCLUSIONS: The fisetin of ATAGJ can markedly suppress Walker 256 cells, and the mechanisms may be intimately associated with the combination of fisetin and AKT. Furthermore, fisetin decreased the level of p-AKT and inhibited the expression of the AKT/HIF-1α signaling pathway.

Study on the molecular mechanism of nightshade in the treatment of colon cancer.

The present study attempts to explore the effective components, action targets, and potential mechanism of nightshade for colon cancer treatment. The relationship network diagram of 'traditional Chinese medicine - component - target - disease' was firstly constructed by employing network pharmacology. Experiments were conducted in vivo and in vitro to verify the influence of quercetin, the core effective component of nightshade, on colon cancer. Meanwhile, the regulatory effects of quercetin on core targets and main signaling pathways were determined. Based on the network diagram of 'traditional Chinese medicine - component - target - disease' and KEGG analysis, quercetin might exhibit certain effects on colon cancer treatment by regulating the biological behavior of core targets related to cell apoptosis in tumors including PIK3R1, PIK3CA, Akt1, and Akt2. Furthermore, quercetin has been demonstrated in vitro experiments to suppress the proliferation and migration of colon cancer cells whereas promote their apoptosis in a dose-dependent fashion. In vivo experiments indicate that quercetin had an antitumor effect on human colon cancer SW480 cells in nude mice bearing tumors. Furthermore, PIK3CA could bind to quercetin directly, which is validated by immunocoprecipitation. Therefore, the activation of PI3K/AKT phosphorylation was inhibited by quercetin and moreover the expressions of apoptotic proteins caspase-3 and Bcl2-Associated X protein (BAX) were up-regulated. In conclusion, the potential mechanism of nightshade lies in the activation of the PI3K/AKT signaling pathway inhibited by quercetin, thus promoting apoptosis of colon cancer cells for colon cancer treatment.

Clinical Effect of Jianpi Yangyin Guse Decoction on Podocin and Nephrin and Its Protection Against Podocyte Injury in Diabetic Nephropathy Patients with Qi and Yin Deficiency / 中国实验方剂学杂志

ObjectiveTo observe the clinical effect of Jianpi Yangyin Guse decoction on patients with diabetic nephropathy （DN），and to explore its protection against podocyte injury. MethodThe enrolled 120 DN patients at stages Ⅲ and Ⅳ and diagnosed with Qi and Yin deficiency from January 2017 to January 2020 were randomly divided into observation group and control group. During the same period，20 healthy volunteers were recruited as the normal group. In addition to the basic treatment in control group，patients in the observation group were given Jianpi Yangyin Guse decoction，and the course of treatment lasted for 3 months. The traditional Chinese medicine （TCM）syndrome score，24 h urine protein （24 h UP），urine albumin-to-creatinine ratio（UACR），liver and renal functions，D-dimer， hemoglobin A1c （HbA1c）， urine podocin and nephrin and α-smooth muscle actin （α-SMA） excretion of the two groups were observed before and after treatment，and the changes were statistically analyzed and compared with those in the normal group. ResultAfter treatment，the reduction of TCM syndrome score in the observation group was more significant than that in the control group（P<0.01）. The 24 h UP level，UACR and renal function in the observation group in the 2nd and 3rd months after treatment were lower than the conditions before treatment（P<0.05）， and those in the 3rd month after treatment were decreased compared with the conditions in the control group during the same period. The levels of podocin and nephrin in each month and the α-SMA excretion in the 3rd month after treatment in the observation group were down-regulated compared with the conditions before treatment and in the control group （P<0.05）， and the observation group had reduced α-SMA excretion in the 2nd month after treatment compared with before treatment. There were no marked changes in D-dimer and liver function of the two groups before and after treatment. The level of HbA1c in the observation group was higher than that in the control group after treatment（P<0.05）. ConclusionJianpi Yangyin Guse decoction has desirable clinical efficacy in DN patients，and its mechanism may be related to reducing podocin and nephrin and α-SMA excretion levels.