Research Progress on Mechanisms of Triggeringreceptor Expressed on Myeloid Cells-2 in Cognitive Dysfunction / 中山大学学报(医学科学版)

The neuroimmune system is crucial for the development， aging， and damage of the central nervous system， and has gradually become a research hotspot. Triggeringreceptor expressed on myeloid cells-2 （TREM2） is a transmembrane receptor of the immunoglobulin superfamily and is mainly expressed in the microglia in the central nervous system. An increasing number of studies indicate that TREM2 has great potential to improve cognitive dysfunction related to Alzheimer's disease， vascular dementia， Parkinson's disease， postoperative cognitive impairment， obesity， etc. However， there is a lack of a systematic summary of the specific role of TREM2 in cognitive dysfunction. This paper reviews the progress in the latest research on the related mechanisms of TREM2 in cognitive dysfunction， in order to provide new strategies for the treatment of cognitive dysfunction.

Transcutaneous Electrical Acupoint Stimulation Promotes PGC-1α Mediated Mitochondrial Biogenesis and Antioxidant Stress to Protect Cognitive Function in Vascular Dementia Rats / 生物化学与生物物理进展

ObjectiveThe purpose of this study was to investigate the effects of transcutaneous electrical acupoint stimulation (TEAS) on cognitive function of vascular dementia (VD) rats and its mechanism. MethodsVD rat model was established by modified two-vessel occlusion (2-VO). After modeling, TEAS and electroacupuncture (EA) were used to stimulate Baihui and Zusanli points of rats respectively for 14 d. After treatment, novel object recognition test, Morris water maze test, and Y maze test were used to evaluate the spatial memory and learning ability of rats. Hematoxylin and eosin staining was used to observe the morphology of hippocampal neurons. Transmission electron microscopy was used to observe the ultrastructure of hippocampal mitochondria. Enzyme-linked immunosorbent assay kits were used to detected the levels of SOD, CAT, GSH-Px, MDA and ROS in serum of rats. Western blot was used to detect the expression of PGC-1α, TFAM, HO-1, NQO1 proteins in the hippocampus, Keap1 protein in the cytoplasm and Nrf2, NRF1 proteins in the nucleus. ResultsAfter treatment for 14 d, compared to the model group, the escape latency of VD rats decreased, while the discrimination index, the times of rats crossing the original platform area, the residence time in the original platform quadrant, and the percentage of alternation increased. TEAS can improve the structure of hippocampal neurons and mitochondria of VD rats, showing that neurons were arranged more regularly and distributed more evenly, nuclear membrane and nucleoli were clearer, and mitochondrial swelling were reduced, mitochondrial matrix density were increased, and mitochondrial cristae were more obvious. The levels of SOD, GSH-Px and CAT in serum increased significantly, while the concentration of MDA and ROS decreased. TEAS also up-regulated the expression levels of PGC-1α TFAM, NQO1 and HO-1 proteins in the hippocampus and Nrf2, NRF1 proteins in the nucleus, but down-regulated the Keap1 protein in the cytoplasm. ConclusionTEAS can improve cognition, hippocampal neurons and mitochondrial structure of VD rats, and the effect is better than EA. The mechanism may be the activation of PGC-1α mediated mitochondrial biogenesis and antioxidant stress, which also provides a potential therapeutic technology and experimental basis for the treatment of VD.

A Methodological Investigation of Hair Proteomics-based Differentiation of Individual Traits / 生物化学与生物物理进展

ObjectiveHair is an essential skin appendage, primarily composed of keratins and keratin-associated proteins. The protein composition and proportion of hair samples vary among different races and sexes. Currently, there is a lack of efficient methods to extract hair proteins. This study aims to explore the application of quantitative hair proteomics in distinguishing individual hair characteristics. MethodsBased on the exploration of sample processing and lysis buffer using three hair samples, we developed a stable and efficient hair protein extraction method, named PLEE (PTM lab for protein extraction from hair with high efficiency). We used the PLEE method to extract seven human hair samples and performed proteomic experiments on them using in-gel digestion method to produce data for analyzing hair protein composition and proportion among individuals. ResultsA total of 274 proteins were identified, among which 107 proteins were commonly present, and the number of non-common proteins ranged from 57-119, with some samples having unique identification proteins. Using the 107 commonly identified proteins for quantitative protein fractionation analysis, various samples were distinguished by clustering and principal component analysis, and technical repeated samples were merged, indicating the stability of the process. In addition, 10 key proteins (KRT33A, KRTAP9-6, KRT83, KRTAP7-1, KRT32, BLMH, KRT38, KRTAP11-1, NPAS1, KRTAP4-3) with large differences between individuals and stable protein identification within the same individual were screened. ConclusionThe protein composition of hair varies among different individuals, and the 10 selected proteins are expected to be key proteins for distinguishing individual hair characteristics and have significant potential applications in individual identification and criminal investigation.

Establishment and genotype identification of hepatic stellate cell-specific Grk2 gene knockout mouse model / 中国药理学通报

Aim To establish a stable hepatic stellate cell ( HSC ) -specific G protein-coupled receptor kinase 2 ( GRK2 ) knockout mice and provide the important animal model for further studying the biological function of GRK2 in HSC. Methods The loxP-labeled Grk2 gene mouse (Grk2

Analysisof neurological disease spectrum among hospitalized patients in a tertiary hospital from 2018 to 2022 / 现代医院

Objective To analyze the changes in the disease spectrum of hospitalized patients with neurological diseases in a tertiary hospital in the past 5 years,in order to effectively develop targeted disease prevention and treatment strategies.Methods Collect case data of neurological diseases in a tertiary hospital from January 1,2018 to December 31,2022,and use ICD-10 coding for disease classification,and analyze the disease type,gender,age groups,and other factors.Results A total of 9060 patients with neurological diseases were admitted in the past five years.In 2020,the number of discharged patients affected by the COVID-19 was the smallest,accounting for 15.96% ,and in 2022,the number was the largest,accounting for 24.05% .The number of cases showed an increasing trend.There was no statistically significant difference in the composition of male and female patients;There is a statistically significant difference in the number of cases among patients of different age groups,and the incidence categories are different;The top 10 diseases in the ranking of neurological diseases are:transient ischemic attack,headache,spinal nerve disease,neurological disorders,epilepsy,Parkinson's disease,sleep disorders,paralysis,other brain diseases,hydrocephalus.The distribution of the top 10 diseases by gender has statistical significance.Conclusion The hospital can formulate the diagnosis and treatment technology for different age groups according to the distribution characteristics of disease spectrum,carry out comprehensive prevention and treatment measures for key groups,strengthen the construction of key special-ties and allocate health resources properly.

Clinical diagnosis, treatment, and genetic analysis in 4 cases of congenital hyperinsulinemia / 中国新生儿科杂志

Objective:To investigate the clinical diagnosis, treatment, and genetic variations of neonates with congenital hyperinsulinism (CHI).Methods:The clinical data of CHI newborns admitted to the Provincial Hospital Affiliated to Shandong First Medical University from September 2018 to April 2022 were retrospectively analyzed.Results:Four cases of CHI were included, three of whom were full-term infants and all were macrosomic, while one was a premature infant. One infant was born to a mother with gestational diabetes mellitus, and 1 had a family history of hypoglycemia. All the 4 patients presented with weak response, 3 with drowsiness, 1 with hypotonia and 1 with convulsions. Cranial MRI indicated abnormal signals in the occipital lobe cortex in 1 case. Gene sequencing revealed homozygous variation c.799C>G in KCNJ11 gene for 1 case, and heterozygous variations c.4477C>T, c.3540C>G, c.683G>A and c.4536C>A in ABCC8 gene for 3 cases respectively and all these variations were identified as pathogenic mutations. Notably, the c.799C>G variant in KCNJ11 gene as well as the c.3540C>G and c.4536C>A variants in ABCC8 gene were reported for the first time. Among infants with ABCC8 gene variations, two showed no response to diazoxide treatment while one patient with KCNJ11 gene variation responded effectively. The parents of the patient with hypoglycemic brain injury gave up treatment. Three other cases were discharged from hospital after improvement and followed up to 1 year old. 2 patients had stable blood glucose after ceasing medication, and 1 patient still required intermittent oral glucose to maintain normal blood glucose level.Conclusions:CHI can lead to hypoglycemic brain injury. Clinically, infants large for gestational age or with a family history of diabetes and hypoglycemia should be monitored for blood glucose early after birth, to identify CHI as early as possible and actively treat it. Different gene variants have different therapeutic responses.

Serum TSH levels in women aged 40 and above : association with lifespan and 10-year mortality / 中华内分泌代谢杂志

Objective:To investigate the relationship between thyroid-stimulating hormone(TSH) levels and 10-year mortality in women aged 40 years and older.Methods:Residents aged 40 and over in urban areas of Guiyang City who participated in the " Epidemiological Study of Cancer Risk in Patients with Type 2 Diabetes in China(REACTION)" were followed up in 2011. Finally, 5 614 people were enrolled, and the baseline general information, physical examination and TSH detection were carried out. The average follow-up was(9.77±1.55) years, and the treatment and death of thyroid-related diseases were recorded. The Cox proportional hazards model was used to analyze the relationship between TSH level and 10-year mortality in middle-aged and elderly women, and plotting survival time curves(Kaplan-Meier curves) to study the association between elevated TSH levels and lifespan in subjects under 65 years old. Results:The multivariate Cox proportional hazards model showed that compared with the normal group, after multivariate adjustment, the risk of death in the TSH increased group was decreased( HR=0.644, 95% CI 0.478-0.868, P<0.05); after stratifying the elevated TSH group, the risk of death was decreased in the slightly elevated TSH group( HR=0.566, 95% CI 0.405-0.791, P<0.001); the elevated TSH group was further stratified by age. In the group under 65 years old, compared to the normal group, the mildly elevated group showed a reduced risk of mortality( HR=0.429, 95% CI 0.245-0.751, P=0.003). In the group aged 65 and above, there were no statistically significant differences in mortality risk between the mildly elevated group, severely elevated group, and the normal group( P>0.05). In the group under 65 years old, the K-M curve indicated that the survival rate of the mildly elevated TSH group was significantly higher than that of the normal group( χ2=11.931, P=0.003), the difference was statistically significant. Conclusion:Mildly elevated TSH levels in women aged 40-65 years are associated with a reduced risk of all-cause death and longer lifespan.

Relationship Between Mindfulness and Affiliate Stigma in Parents of Children with Autism Spectrum Disorder in China: The Mediating Role of Coping Styles

Purpose@#This study aims to investigate the current status of affiliate stigma among parents of autistic children, analyze the influencing factors, explore the relationship among mindfulness, coping styles, and affiliate stigma, and verify the mediating role of coping styles between mindfulness and affiliate stigma in parents of children with autism in China.MethodBetween February and April 2023, the Child Development Behaviour Centre of a public hospital in China recruited 345 parents of children with autism. These parents completed the general information questionnaire, the Mindful Attention Awareness Scale, the Affiliate Stigma Scale, and the Simple Coping Style Questionnaire. We then adapted the Hayes Process Macro and Bootstrap methods to examine the mediating effects of coping styles between mindfulness and affiliate stigma. @*Results@#(1) The total affiliate stigma score of parents of children with autism was 48.53 (standard deviation:: 10.74). Parents' age, monthly family income, duration of care, mindfulness, and coping styles were the influencing factors of parental affiliate stigma. (2) Mindfulness was positively correlated with positive coping style (r = 0.33, p < .01) and negatively correlated with negative coping style, affiliate stigma (r = −0.38, −0.39, p < .01), whereas affiliate stigma was negatively correlated with positive coping style (r = −0.34, p < .01) and positively correlated with negative coping style (r = 0.41, p < .01). (3) Positive coping style and negative coping style play a parallel mediating role between mindfulness and affiliate stigma of parents of autistic children. @*Conclusions@#Parents of children with autism experience significant levels of affiliate stigma. Mindfulness has a direct impact on associated stigma in parents of children with autism and also indirectly predicts associated stigma through the intermediary influence of positive and negative coping styles. Healthcare professionals could perform mindfulness interventions from an optimistic psychology viewpoint to boost parents' mindfulness and coping abilities, thereby accomplishing the objective of mitigating affiliate stigma.

Treatment responses, outcomes, and prognostic factors associated with them in patients with secondary acute myeloid leukemia / 中华血液学杂志

Objective: To evaluate treatment responses, outcomes, and prognostic factors in adults with secondary acute myeloid leukemia (sAML) . Methods: Between January 2008 and February 2021, date of consecutive cases of younger than 65 years of adults with sAML were assessed retrospectively. Clinical characteristics at diagnosis, treatment responses, recurrence, and survival were evaluated. Logistic regression and Cox proportional hazards model were employed to determine significant prognostic indicators for treatment response and survival. Results: 155 patients were recruited, including 38, 46, 57, 14 patients belonging to t-AML, and AML with unexplained cytopenia, post-MDS-AML, and post-MPN-AML, respectively. In the 152 evaluable patients, the rate of MLFS after the initial induction regimen was 47.4%, 57.9%, 54.3%, 40.0%, and 23.1% in the four groups (P=0.076) . The total rate of MLFS after the induction regimen was 63.8%, 73.3%, 69.6%, 58.2%, and 38.5% (P=0.084) , respectively. Multivariate analysis demonstrated that male gender (OR=0.4, 95% CI 0.2-0.9, P=0.038 and OR=0.3, 95% CI 0.1-0.8, P=0.015) , SWOG cytogenetic classification into unfavorable or intermediate (OR=0.1, 95% CI 0.1-0.6, P=0.014 and OR=0.1, 95% CI 0.1-0.3, P=0.004) and receiving low-intensity regimen as induction regimen (OR=0.1, 95% CI 0.1-0.3, P=0.003 and OR=0.1, 95%CI 0.1-0.2, P=0.001) were typical adverse factors impacting the first CR and the final CR; PLT<45 × 10(9)/L (OR=0.4, 95%CI 0.2-0.9, P=0.038) and LDH ≥258 U/L (OR=0.3, 95%CI 0.1-0.7, P=0.005) were independent factors for CR. Among the 94 patients with achieving MLFS, 46 cases had allogeneic hematopoietic stem cell transplantation. With a median follow-up period of 18.6 months, the probabilities of relapse-free survival (RFS) and overall survival (OS) at 3 years were 25.4% and 37.3% in patients with transplantation, and in patients with chemotherapy, the probabilities of RFS and OS at 3-year were 58.2% and 64.3%, respectively. At the time of achieving MLFS, multivariate analysis revealed that age ≥46 years (HR=3.4, 95%CI 1.6-7.2, P=0.002 and HR=2.5, 95%CI 1.1-6.0, P=0.037) , peripheral blasts ≥17.5% at diagnosis (HR=2.5, 95%CI 1.2-4.9, P=0.010 and HR=4.1, 95%CI 1.7-9.7, P=0.002) , monosomal karyotypes (HR=4.9, 95%CI 1.2-19.9, P=0.027 and HR=28.3, 95%CI 4.2-189.5, P=0.001) were typical adverse factors influencing RFS and OS. Furthermore, CR after induction chemotherapy (HR=0.4, 95%CI 0.2-0.8, P=0.015) and transplantation (HR=0.4, 95%CI 0.2-0.9, P=0.028) were substantially linked to longer RFS. Conclusion: Post-MDS-AML and post-MPN-AML had lower response rates and poorer prognoses than t-AML and AML with unexplained cytopenia. In adults with male gender, low platelet count, high LDH, and SWOG cytogenetic classification into unfavorable or intermediate at diagnosis, and receiving low-intensity regimen as the induction regimen predicted a low response rate. Age ≥46 years, a higher proportion of peripheral blasts and monosomal karyotype had a negative effect on the overall outcome. Transplantation and CR after induction chemotherapy were greatly linked to longer RFS.

Clinical and genetic characteristics of 9 rare cases with coexistence of dual genetic diagnoses / 中华儿科杂志

Objective: To analyze the clinical and genetic characteristics of pediatric patients with dual genetic diagnoses (DGD). Methods: Clinical and genetic data of pediatric patients with DGD from January 2021 to February 2022 in Peking University First Hospital were collected and analyzed retrospectively. Results: Among the 9 children, 6 were boys and 3 were girls. The age of last visit or follow-up was 5.0 (2.7,6.8) years. The main clinical manifestations included motor retardation, mental retardation, multiple malformations, and skeletal deformity. Cases 1-4 were all all boys, showed myopathic gait, poor running and jumping, and significantly increased level of serum creatine kinase. Disease-causing variations in Duchenne muscular dystrophy (DMD) gene were confirmed by genetic testing. The 4 children were diagnosed with DMD or Becker muscular dystrophy combined with a second genetic disease, including hypertrophic osteoarthropathy, spinal muscular atrophy, fragile X syndrome, and cerebral cavernous malformations type 3, respectively. Cases 5-9 were clinically and genetically diagnosed as COL9A1 gene-related multiple epiphyseal dysplasia type 6 combined with NF1 gene-related neurofibromatosis type 1, COL6A3 gene-related Bethlem myopathy with WNT1 gene-related osteogenesis imperfecta type XV, Turner syndrome (45, X0/46, XX chimera) with TH gene-related Segawa syndrome, Chromosome 22q11.2 microduplication syndrome with DYNC1H1 gene-related autosomal dominant lower extremity-predominant spinal muscular atrophy-1, and ANKRD11 gene-related KBG syndrome combined with IRF2BPL gene-related neurodevelopmental disorder with regression, abnormal movement, language loss and epilepsy. DMD was the most common, and there were 6 autosomal dominant diseases caused by de novo heterozygous pathogenic variations. Conclusions: Pediatric patients with coexistence of double genetic diagnoses show complex phenotypes. When the clinical manifestations and progression are not fully consistent with the diagnosed rare genetic disease, a second rare genetic disease should be considered, and autosomal dominant diseases caused by de novo heterozygous pathogenic variation should be paid attention to. Trio-based whole-exome sequencing combining a variety of molecular genetic tests would be helpful for precise diagnosis.

Clinical analysis of the usefulness of letermovir for prevention of cytomegalovirus infection after haploidentical hematopoietic stem cell transplantation / 中华内科杂志

Objective: To analyze the efficacy and safety of letermovir in primary prophylaxis of cytomegalovirus (CMV) reactivation in patients receiving haploidentical hematopoietic stem cell transplantation. Methods: This retrospective, cohort study was conducted using data of patients who underwent haploidentical transplantation at Peking University Institute of Hematology and received letermovir for primary prophylaxis between May 1, 2022 and August 30, 2022. The inclusion criteria of the letermovir group were as follows: letermovir initiation within 30 days after transplantation and continuation for≥90 days after transplantation. Patients who underwent haploidentical transplantation within the same time period but did not receive letermovir prophylaxis were selected in a 1∶4 ratio as controls. The main outcomes were the incidence of CMV infection and CMV disease after transplantation as well as the possible effects of letermovir on acute graft versus host disease (aGVHD), non-relapse mortality (NRM), and bone marrow suppression. Categorical variables were analyzed by chi-square test, and continuous variables were analyzed by Mann-Whitney U test. The Kaplan-Meier method was used for evaluating incidence differences. Results: Seventeen patients were included in the letermovir prophylaxis group. The median patient age in the letermovir group was significantly greater than that in the control group (43 yr vs. 15 yr; Z=-4.28, P<0.001). The two groups showed no significant difference in sex distribution and primary diseases, etc. (all P>0.05). The proportion of CMV-seronegative donors was significantly higher in the letermovir prophylaxis group in comparison with the control group (8/17 vs. 0/68, χ2=35.32, P<0.001). Three out of the 17 patients in the letermovir group experienced CMV reactivation, which was significantly lower than the incidence of CMV reactivation in the control group (3/17 vs. 40/68, χ2=9.23, P=0.002), and no CMV disease development observed in the letermovir group. Letermovir showed no significant effects on platelet engraftment (P=0.105), aGVHD (P=0.348), and 100-day NRM (P=0.474). Conclusions: Preliminary data suggest that letermovir may effectively reduce the incidence of CMV infection after haploidentical transplantation without influencing aGVHD, NRM, and bone marrow suppression. Prospective randomized controlled studies are required to further verify these findings.

Voltage Dependent Anion Channel 1 Mediated Inflammation and Obstructive Sleep Apnea Syndrome / 中山大学学报(医学科学版)

VDAC1（voltage dependent anion channel 1）is an important channel protein on the outer mitochondrial outer membrane， which regulates mitophagy， participates in the regulation of inflammatory cytokines and the activation of the inflammasome， hence being crucial to the inflammatory response. Patients with obstructive sleep apnea syndrome （OSAS） suffer neuroinflammation due to intermittent hypoxia and increased oxidative stress， leading to chronic damage and neuronal cell apoptosis， and eventually develop cognitive impairment. Since OSAS patients' cognitive impairment is significantly influenced by inflammation， and VDAC1 regulates the activation of the inflammasome， the relationship between OSAS and VDAC1， mitophagy， as well as inflammation are reviewed here. We hope that this study can provide a new breakthrough in mitophagy and inflammation in patients with cognitive dysfunction caused by OSAS.

Risk factors and complication of hemodynamically significant patent ductus arteriosus in preterm infants with gestational age <32 weeks / 国际儿科学杂志

Objective:To study the risk factors and complications of hemodynamically significant patent ductus arteriosus(hsPDA)in preterm infants <32 weeks.Methods:From January 2021 to March 2022, a total of 150 premature infants with gestational age <32 weeks admitted to the Neonatal Intensive Care Unit of Liaocheng People′s Hospital were enrolled.Nine patients who did not meet the requirements were excluded and a total of 141 infants were finally analyzed retrospectively, including PDA group with 95 cases and non-PDA group with 46 cases.According to whether hsPDA existed or not, PDA group were dirided into hsPDA group with 42 cases and non-hsPDA group with 53 cases.Univariate and regression analyses were used to determine the risk factors and complication of hsPDA.Results:Univariate analysis showed that gestational age( t=-6.861, P<0.01), birth weight( t=-4.392, P<0.01), mode of delivery( χ2=9.018, P<0.01), caffeine( χ2=4.337, P<0.05) and suffocation( χ2=7.918, P<0.01)were associated with hsPDA.Logistic regression analysis showed that gestational age( OR=2.435, P<0.01, 95% CI: 1.669~3.552)was an independent risk factor for hsPDA in gestational age <32 weeks preterm infants.The incidences of necrotizing enterocolitis, intraventricular hemorrhage, bronchopulmonary dysplasia, and retinopathy of prematurity in the hsPDA group were higher than those in the non-hsPDA group( P<0.05). Conclusion:Gestational age is an independent risk factor for hsPDA with gestational age <32 weeks.Necrotizing enterocolitis, intraventricular hemorrhage, bronchopulmonary dysplasia, and retinopathy of prematurity are related complications of hsPDA.

Status quo and influencing factors of grief in maternal spouses after perinatal loss / 中国实用护理杂志

Objective:To investigate the status of grief among maternal spouse after perinatal loss, and analyze its influencing factors, so as to provide some reference for male grief supporting strategic.Methods:Using the convenient sampling method, 180 male spouses of hospitalized women in the Department of Obstetrics from Nanjing Maternity and Child Health Care Hospital from March to October 2022 were recruited. A cross-sectional survey was conducted by the general questionnaire, the Perinatal Grief Scale, the Family Adaptability and Cohesion Scale Ⅱ-Chinese Version, the Social Support Rating Scale, and the Simplified Coping Style Questionnaire.Results:The overall score of the Perinatal Grief Scale in male spouses of women who experienced a perinatal loss was (61.57 ± 14.14) points. The score of the Family Adaptability and Cohesion Scale Ⅱ-Chinese Version was (121 ± 14.42) points, the score of the Social Support Rating Scale was (34.23 ± 7.21) points, and the score of the Simplified Coping Style Questionnaire was (36.08 ± 7.64) points. Multiple linear regression analysis showed that participation in fetal interaction, loss of fetal age, social support and family adaptability were the main factors affecting male grief ( P<0.05). Conclusions:The grief among male spouses of women who experienced a perinatal loss is at a low level. The clinical medical staff can refer to the influencing factors and implement effective support, such as respecting the male's father status, coordinating social support resources, and improving the family's coping ability, in order to alleviate men's grief and help them return to normal life.

A nomogram based on CT enterography signs for prediction of intestinal penetrating lesions in patients with Crohn disease / 中华放射学杂志

Objective:To explore the value of a nomogram model based on the CT enterography (CTE) signs for prediction of intestinal penetrating lesions in patients with Crohn disease (CD).Methods:The clinical and CTE data of CD patients who underwent at least two CTE examinations from January 2010 to June 2020 in the First Affiliated Hospital of Sun Yat-sen University were retrospectively collected. A total of 112 patients were enrolled, and according to whether there was intestinal wall penetration in the last CTE observation were divided into non-penetration group (84 cases) and penetration group (28 cases). First, the clinical and CTE data for the first examination was analyzed by using univariate and multivariate Cox proportional hazards regression to screen out high-risk factors that could effectively predict intestinal wall penetrating lesions in CD patients and established a nomogram model. Then the change trend of CTE data (ΔCTE) between the first and last clinical and CTE signs was analyzed by using univariate and multivariate Cox proportional hazards regression, and built a nomogram model to sort out ΔCTE that may accompany the development of penetrating lesions in CD patients. The Harrell concordance index was used to evaluate the discriminative ability of the nomogram model.Results:In the first time clinical and CTE signs, multivariate Cox proportional hazards regression results showed that numbers of diseased bowel segments (HR=0.686, 95%CI 0.475-0.991, P=0.045) and the shortest diameter of the largest lymph node (HR=0.751, 95%CI 0.593-0.949, P=0.017) were independent protection factors for penetrating lesions, and rough bowel wall surface (HR=5.626, 95%CI 2.466-12.839, P<0.001) was an independent risk factor for penetrating lesions. The specificity and sensitivity of the nomogram model to predict non-penetration lesions were 82.1% and 59.5% respectively, and the Harrell concordance index was 0.810 (95%CI 0.732-0.888). In the ΔCTE signs, multivariate Cox proportional hazards regression showed that Δrough bowel wall surface (always rough bowel wall surface HR=12.344, 95%CI 2.042-74.625, P=0.006; slide bowel wall surface becomes rough bowel wall surface HR=28.720, 95%CI 4.580-180.112, P<0.001) and Δthe shortest diameter of the largest lymph node (HR=1.534, 95%CI 1.091-2.157, P=0.014) were independent risk factors for penetrating lesions. The specificity and sensitivity of the nomogram model were 89.3% and 79.2% respectively, and the Harrell concordance index was 0.876 (95%CI 0.818-0.934). Conclusion:The nomogram based on CTE signs of numbers of diseased bowel segments, the shortest diameter of the largest lymph node and rough bowel wall surface and ΔCTE can effectively predict the intestinal wall penetrating lesions of CD patients.

Effect of Yin Yang protein 1 transcriptionally regulating acetyl-CoA carboxylase 1 on the cell migration and lipogenesis in ovarian cancer / 肿瘤研究与临床

Objective:To investigate the expression of acetyl-CoA carboxylase 1 (ACC1) in ovarian cancer tissues and cells, and the related mechanisms of the effect of ACC1 on cell migration and lipogenesis in ovarian cancer.Methods:Samples including 1 case of normal ovarian tissue, 1 case of ovarian cancer primary lesion tissue and 1 case of ovarian cancer omentum metastatic tissue diagnosed by pathology examination of patients undergoing surgery resection who admitted to Linyi Cancer Hospital between January 2019 and December 2021 were collected. Immunohistochemistry was used to detect the protein levels of ACC1 and Yin Yang protein 1 (YY1) of all tissues. The PROMO database was used to predict the possible binding sites of YY1 and ACC1 promoter region. Through the assembled viral vector, the HEY cells of human ovarian cancer with ACC1 or YY1 expression [the untreated cells were treated as the negative control (NC)], or knocked down ACC1 or YY1 (the interference sequence sh1, sh2, sh3 was transferred to the target gene, and the negative control sequence shNC was transferred to the interference sequence). Double luciferase reporter gene assay was used to verify the binding sites of YY1 and ACC1 promoter and the activity of transcriptional regulation. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) and Western blot were used to detect the mRNA and protein expression levels of ACC1 and YY1 in the treated HEY cells, respectively. Transwell assay was used to detect the migration ability of HEY cells. Oil red O staining and Nile red staining were used to detect the lipid droplets in HEY cells.Results:The immunohistochemical scores of ACC1 and YY1 were 0, 2, 8 scores and 0, 4, 6 scores, respectively in normal ovarian tissue, primary lesion of ovarian cancer, and omentum metastatic tissue. Transwell assay showed that the number of invasive HEY cells in ACC1 overexpression group was more than that in NC group [(87.7±7.4) vs. (52.2±4.2), t = 5.19, P = 0.003]. The number of invasive HEY cells in ACC1-sh1 group, and ACC1-sh2 group with the knockdown of ACC1 was less than that in shNC group [(21.2±1.5), (29.7±2.3) vs. (56.2±5.3); t value was 6.41, 3.77; P < 0.001, P < 0.005]. The number of lipid droplets in HEY cells in the ACC1 overexpression group was more than that in the control NC group [Oil red O staining: (301±25) vs. (215±21); Nile red staining: (287±15) vs. (207±10); all P < 0.05]; the number of lipid droplets in HEY cells in ACC1-sh1 and ACC1-sh2 group with the knockdown of ACC1 was less than that in ACC1-shNC group [Oil red O staining: (113±8), (119±12) vs. (195±18); Nile red staining: (82±8), (117±11) vs. (165±17); all P < 0.05]. The result of dual luciferase reporter assay showed that overexpression of YY1 promoted the luciferase activity of the wild type ACC1 promoter region report gene ( P = 0.003), while the luciferase activity of the report gene was inhibited compared with the wild type after the mutation of binding sites of YY1 in ACCI promoter region ( P = 0.008). Western blot results showed that the expression levels of YY1 and ACC1 protein in HEY cells with YY1 overexpression group were higher than those in NC group, which indicated a synergistic increasing trend of both YY1 and ACC1; the expression levels of YY1 and ACC1 protein in YY1-sh1 group, YY1-sh2 group and YY1-sh3 group with the knockdown of YY1 were lower than those in the control YY1-shNC group, which indicated a synergistic decreasing trend of both YY1 and ACC1. Conclusions:ACC1 and YY1 are highly expressed in ovarian cancer metastatic tissues and both show a positive correlation trend. The expression level of ACC1 in vitro has an impact on cell migration and lipogenesis in ovarian cancer via YY1 transcriptionally regulating ACC1.

Stigma and Efficacy of Zhizhu Kuanzhong Capsules Versus Doxepin in the Treatment of Refractory Functional Dyspepsia: A Randomized Controlled Trial

Background/Aims@#Stigma related with antidepressants is prevalent in patients with functional dyspepsia. It affects medication compliance and efficacy.Herbal medicine acquired a deep-rooted cultural identity in relieving dyspeptic symptoms in Asians. The research was designed to compare the effectiveness of Zhizhu Kuanzhong capsules (ZZKZ) versus doxepin hydrochloride (doxepin) on alleviating stigma and medication nonadherence among patients with refractory FD (rFD). @*Methods@#Patients with rFD from February 2021 to February 2022 were randomly allocated to receive either doxepin (n = 56) or ZZKZ (n = 57) combined with omeprazole for 4 weeks. Medication possession ratio (MPR), the disease- and medication-associated stigma were analyzed. The scales were utilized to assess dyspeptic symptoms (Leeds Dyspepsia Questionnaire) and psychological conditions (Generalized Anxiety Disorder Questionnaire and Patient Health Questionnaire). @*Results@#The MPR values for ZZKZ were significantly higher than those for doxepin (P < 0.001). The stigma scores decreased in ZZKZ group while increased in doxepin group compared to baseline after treatment. The proportion of patients showing ZZKZ-associated stigma was significantly lower than doxepin-associated stigma (P < 0.001). The MPR values were negatively correlated with posttreatment stigma scores in both groups (P < 0.001). Dyspeptic symptoms and psychological condition were improved in both groups after treatment, with no significant difference on post-treatment Leeds Dyspepsia Questionnaire, Generalized Anxiety Disorder Questionnaire, or Patient Health Questionnaire scores between 2 groups. @*Conclusion@#ZZKZ is superior to doxepin in alleviating stigma and medication non-adherence, with comparable efficacy in improving dyspeptic symptoms and psychological condition of patients with rFD.

Structural distribution and mechanism of elastic fibers and collagen fibers in ventricular interstitium of aged rats / 解剖学报

Objective To investigate the structural distribution features and mechanism of elastic fibers and collagen fibers in ventricular interstitium of aged rats. Methods Five young SD rats (24 weeks) and five old SD rats (104 weeks) were used,and their cardiac function was examined by echocardiography. Modified Weigert elastic fiber staining, immunohistochemistry, immunofluorescence and Western blotting techniques were used to detect the expression changes of type I and IH collagen fibers and their proteins, elastic fibers and their proteins, matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase 2 (TIMP-2), respectively. Results The type I and type IH collagen in the ventricular interstitium of aged rats was very sufficient and wrapped around the cardiomyocytes. Compared with the young rats, the content of collagen protein in the ventricular interstitium of the aged rats significantly increased (P<0. 05). Elastic fibers in the ventricular interstitium of the aged rats were and widely distributed. Compared with the young rats, the number of elastic fibers and the level of elastin in the ventricular interstitium of the aged rats significantly decreased (P<0. 05), and the expression levels of MMP-2 and MMP-9 in ventricular muscle of aged rats increased, and the)' were correlated with the level of elastin. The level of TIMP-2 in ventricular muscle of aged rats decreased with age. Conclusion The number of collagen fibers and elastic fibers in ventricular interstitium of aged rats is fluctuated with each other. With the increase of age, the contents of TIMP-2 and elastic fibers in the ventricular interstitium gradually decreased, and the ratio of collagen fibers to elastic fibers is out of balance.

Chinese consensus guidelines for therapeutic drug monitoring of polymyxin B, endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Polymyxin B, which is a last-line antibiotic for extensively drug-resistant Gram-negative bacterial infections, became available in China in Dec. 2017. As dose adjustments are based solely on clinical experience of risk toxicity, treatment failure, and emergence of resistance, there is an urgent clinical need to perform therapeutic drug monitoring (TDM) to optimize the use of polymyxin B. It is thus necessary to standardize operating procedures to ensure the accuracy of TDM and provide evidence for their rational use. We report a consensus on TDM guidelines for polymyxin B, as endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society. The consensus panel was composed of clinicians, pharmacists, and microbiologists from different provinces in China and Australia who made recommendations regarding target concentrations, sample collection, reporting, and explanation of TDM results. The guidelines provide the first-ever consensus on conducting TDM of polymyxin B, and are intended to guide optimal clinical use.

Clinical analysis of liver dysfunction induced by SHR-1210 alone or combined with apatinib and chemotherapy in patients with advanced esophageal squamous cell carcinoma / 中华肿瘤杂志

Objective: To investigate the clinical characteristics of abnormal liver function in patients with advanced esophageal squamous carcinoma treated with programmed death-1 (PD-1) antibody SHR-1210 alone or in combination with apatinib and chemotherapy. Methods: Clinical data of 73 patients with esophageal squamous carcinoma from 2 prospective clinical studies conducted at the Cancer Hospital Chinese Academy of Medical Sciences from May 11, 2016, to November 19, 2019, were analyzed, and logistic regression analysis was used for the analysis of influencing factors. Results: Of the 73 patients, 35 had abnormal liver function. 13 of the 43 patients treated with PD-1 antibody monotherapy (PD-1 monotherapy group) had abnormal liver function, and the median time to first abnormal liver function was 55 days. Of the 30 patients treated with PD-1 antibody in combination with apatinib and chemotherapy (PD-1 combination group), 22 had abnormal liver function, and the median time to first abnormal liver function was 41 days. Of the 35 patients with abnormal liver function, 2 had clinical symptoms, including malaise and loss of appetite, and 1 had jaundice. 28 of the 35 patients with abnormal liver function returned to normal and 7 improved to grade 1, and none of the patients had serious life-threatening or fatal liver function abnormalities. Combination therapy was a risk factor for patients to develop abnormal liver function (P=0.007). Conclusions: Most of the liver function abnormalities that occur during treatment with PD-1 antibody SHR-1210 alone or in combination with apatinib and chemotherapy are mild, and liver function can return to normal or improve with symptomatic treatment. For patients who receive PD-1 antibody in combination with targeted therapy and chemotherapy and have a history of long-term previous smoking, alcohol consumption and hepatitis B virus infection, liver function should be monitored and actively managed in a timely manner.