Influence of reminiscence therapy on mental health and quality of life in elderly patients with unresectable, metastatic gastrointestinal cancer

Reminiscence therapy (RT) attenuates psychological disorders in cancer patients. This study aimed to evaluate the effect of RT on anxiety, depression, spiritual well-being, and quality of life in elderly patients with unresectable, metastatic gastrointestinal cancer. A total of 222 elderly patients with unresectable, metastatic gastrointestinal cancer were randomized into RT group (RT plus usual care, n=112) or control group (usual care, n=110) with a 6-month intervention. Hospital Anxiety and Depression Scale for Anxiety (HADS-A) and Depression (HADS-D), Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale (FACIT-Sp), and Quality of Life Questionnaire-Core 30 (QLQ-C30) were evaluated at month (M)0, M1, M3, and M6. Concerning the primary outcome, HADS-A score at M6 decreased in the RT group compared to the control group (P=0.005). As to secondary outcomes, the RT group showed decreased HADS-A scores at M3, anxiety rate at M3, HADS-D scores at M3 and M6, depression rate at M6, as well as greater FACIT-Sp scores at M1, M3, and M6 vs the control group (all P<0.050). Additionally, QLQ-C30 global health score was elevated at M1 (P=0.046) and M6 (P=0.005), functions score was greater at M6 (P=0.038), and symptoms score was lower at M3 (P=0.019) in the RT group than in the control group. Subgroup analysis revealed that the addition of RT was more effective for patients with anxiety or depression at baseline. In summary, RT alleviated anxiety and depression, and improved the spiritual well-being and quality of life within 6 months in elderly patients with unresectable, metastatic gastrointestinal cancer.

Feasibility of a novel type of complex anterior cervical fixation by using Mimics software / 中国骨伤

OBJECTIVE@#To investigate the feasibility of mimics software in analyzing a new type of complex anterior cervical fixation -- anterior transpedicular screw fixation+zero notch internal fixation.@*METHODS@#From January 2021 to September 2022, 50 normal pedestrians who underwent cervical spine CT scanning were selected for C1-C7 segment scanning, including 27 males and 23 females, aged from 25 to 65 years old with an average of (46.0 ± 9.0) years old. The dicom format is exported and engraved into the CD, and use the mimics software to perform 3D reconstruction of each segment. A simulated screw is placed on the image according to the critical value of zero notch screw (head and tail angle 44°, internal angle 29°). The position of zero notch screw in each segment is observed to determine the feasibility of anterior transpedicular screw fixation plus zero notch internal fixation.@*RESULTS@#For the upper zero notch screws the three-dimensional images of the cervical spine across all 50 subjects within the C3-C7 segments demonstrated safe position, with no instances of intersection with ATPS. For the lower zero notch screw, in C3-C4 and C4-C5, 4 out of 50 subjects are in the safe position in the three-dimensional images of cervical vertebrae, and 46 cases could achieve secure screw placement when the maximum caudal angle is(32.3±1.9) ° and (36.1±2.2) °, respectively. In C5-C6 and C6-C7 segments, no lower zero notch screws intersected with ATPS, and all screws are in safe positions.@*CONCLUSION@#Lower cervical anterior pedicle screw fixation plus zero notch internal fixation can achieve successful nail placement through the selected entry point and position.

Aerobic exercise upregulates the thioredoxin system and inhibits cardiomyocyte apoptosis in aging rats / 中国组织工程研究

BACKGROUND:Studies have shown that cardiomyocyte apoptosis is closely related to cardiac decompensation and the cardiac aging process.Appropriate exercise can alter heart pump function in patients with heart failure as well as attenuate aging-induced cardiomyocyte apoptosis,hypertrophy,and fibrotic damage. OBJECTIVE:To investigate the effects of long-term aerobic exercise on cardiomyocyte apoptosis and the thioredoxin system in aging rats. METHODS:Thirty-six male Sprague-Dawley rats were selected and divided into three age groups:3-month-old young group,9-month-old middle-aged group,and 18-month-old elderly group,with 12 rats in each group.Within each age group,rats were randomly assigned to sedentary and exercise subgroups(n=6 per group).The sedentary groups did not undergo any exercise intervention.The exercise groups were acclimated to a treadmill environment and subsequently subjected to treadmill exercise for 45 minutes per day,at a speed of 15 m/min,5 days per week for 10 weeks in total.At 24 hours after the final intervention,ELISA was employed to measure serum levels of cardiac troponin I and creatine kinase-MB in rats.TUNEL assay was utilized to detect cardiomyocyte apoptosis,while western blot assay was employed to assess the protein expression of Bax,Bcl-2,Caspase 3,thioredoxin-1,thioredoxin-2,thioredoxin reductase-1,thioredoxin reductase-2,thioredoxin-interacting protein,apoptosis signal-regulating kinase 1,and P38 mitogen-activated protein kinase in rat myocardial tissue. RESULTS AND CONCLUSION:Serum levels of cardiac troponin I and creatine kinase-MB in the elderly sedentary group were significantly higher than those in the young and middle-aged sedentary groups and elderly exercise group(P<0.01).Serum levels of cardiac troponin I and creatine kinase-MB in the elderly sedentary group were significantly higher than those in the young and middle-aged exercise groups and elderly exercise group(P<0.01).Positive apoptotic cells in rat myocardial tissue,along with increased protein expression of Bax and Caspase 3,exhibited an age-related upward trend,while Bcl-2 protein expression showed a declining trend.In comparison with the sedentary groups within each age category,the number of apoptotic cardiomyocytes and the expression of Bax and Caspase 3 proteins were reduced to different degrees,and the expression of Bcl-2 protein was increased to different degrees in the corresponding exercise groups.Compared with the young sedentary group,middle-aged sedentary group and elderly exercise group,elderly sedentary rats showed a significant decrease in the expression of myocardial thioredoxin 1,thioredoxin 2,thioredoxin reductase 1,and thioredoxin reductase 2 proteins(P<0.05,P<0.01).The expression of myocardial thioredoxin 1,thioredoxin 2,and thioredoxin reductase 2 proteins was lower in the elderly exercise group than in the young exercise group(P<0.05,P<0.01),while the expression of thioredoxin reductase 1 and thioredoxin reductase 2 proteins was lower in the elderly exercise group than in the middle-aged exercise group(P<0.01).The protein expression of thioredoxin-interacting protein,apoptosis signal-regulating kinase 1,and P38 mitogen-activated protein kinase in rat myocardium was significantly higher in the elderly sedentary group than the young sedentary group,middle-aged sedentary group and elderly exercise group(P<0.01).The protein expression of thioredoxin-interacting protein,apoptosis signal-regulating kinase 1,and P38 mitogen-activated protein kinase in rat myocardium was significantly higher in the elderly exercise group than the young exercise group and middle-aged exercise group(P<0.01).To conclude,aerobic exercise may enhance the anti-apoptotic effects of thioredoxin by down-regulating the expression of thioredoxin-interacting protein in aging rat hearts,leading to the downregulation of apoptosis signal-regulated kinase 1 and P38 mitogen-activated kinase protein,thereby alleviating myocardial cell apoptosis in aging rat hearts.

Advances in the internal fixation surgical approach for sacroiliac joint dislocation caused by posterior pelvic ring injury / 局解手术学杂志

Injury of the posterior pelvic ring can easily be caused by high-energy impact,and sacroiliac joint dislocation is the most common.The sacroiliac joint,as the hub of load transfer between the trunk and lower extremities,is essential to maintain the stability of the posterior pelvic ring,and once dislocation occurs,restoring the stability of the posterior pelvic ring by timely surgery is necessary.The current surgical approaches for the internal fixation of sacroiliac joint are mainly divided into anterior approach and posterior approach.The choice of the surgical approach directly affects the exposure of the surgical field,the stability of internal fixation and the prognosis of patients;therefore,it is particularly important to select the appropriate surgical approach and fixation method.In this paper,we briefly review the selection of sacroiliac joint fixation points,surgical approaches and postoperative complications.

Role and Possible Mechanism of Clock Gene Rev-erbα in Exercise-induced Mitochondrial Biogenesis / 生物化学与生物物理进展

The clock gene Rev-erbα, also known as nuclear receptor subfamily 1 group D member 1 (Nr1d1), is a crucial regulatory factor in organisms. It exhibits circadian rhythmic expression in metabolically active tissues such as skeletal muscles, heart, liver, and adipose tissue, responding to various environmental stimuli. Rev-erbα plays a significant role in regulating circadian rhythms, metabolic homeostasis, and other physiological processes, earning its designation as an “integrator” of the circadian system and metabolism. Rev-erbα establishes complex connections with other clock genes through the transcriptional-translational feedback loop (TTFL), which is important for the rhythmic output of biological clock system and for the relative stability of phases and cycles. Mitochondrial biogenesis is a physiological process initiated by cells to maintain energy homeostasis by using existing mitochondria as a template for self-growth and division. As the “energy factory” of organism, disruptions in mitochondrial biogenesis are closely associated with the development of various diseases. Studies have shown that not only the factors involved in mitochondrial biogenesis have circadian oscillations, but also the morphology, dynamics and energy metabolism of mitochondria themselves have cyclic fluctuations throughout the day, suggesting that mitochondrial biogenesis is regulated by the biological clock system, in which the clock gene Rev-erbα plays a key role, it drives mitochondrial biogenesis and synergistically regulates autophagy to normalize a number of physiological processes in the body. Rev-erbα is sensitive to both internal and external environmental changes, and disruptions in circadian rhythms, metabolic diseases, and aging are significant inducers of changes in Rev-erbα expression, and its concomitant inflammation and oxidative stress may be an intrinsic mechanism for inhibiting mitochondrial biogenesis. Therefore, the enhancement of mitochondrial biogenesis by regulating the Rev-erbα activity status may be an important way to improve the pathology and promote the health of organism. Exercise, as a commonly accepted non-pharmacological tool, plays an important role in enhancing mitochondrial biogenesis and promoting health. It has been found that there is a close relationship between exercise and Rev-erbα. On the one hand, exercise stimulation directly affects the expression of Rev-erbα, especially high-intensity and long-term regular exercise; on the other hand, Rev-erbα achieves indirect regulation of exercise capacity by mediating processes such as skeletal muscle mitochondrial biogenesis and autophagy, muscle mass maintenance, energy metabolism and skeletal muscle regeneration. Based on the above findings, it is hypothesized that Rev-erbα may serve as a key bridge between exercise and mitochondrial biogenesis. Exercise enhances the transcriptional response of Rev-erbα in the nucleus, upregulates the expression of Rev-erbα protein in cytoplasm, activates the AMP-activated proteinkinase (AMPK)/ silent information regulator 1 (SIRT1)/peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) pathway, regulates Ca2+ flux and downstream signaling molecules; meanwhile, exercise can upregulate antioxidant gene expression and alleviate oxidative stress through Rev-erbα, which ultimately enhances the function of mitochondria, and promotes mitochondrial biogenesis. In conclusion, the clock gene Rev-erbα emerges as a crucial target for exercise-induced enhancement of mitochondrial biogenesis. In this paper, the biological characteristics ofRev-erbα, the role of Rev-erbα in regulating mitochondrial biogenesis and the factors that may influence it, the interaction between exercise and Rev-erbα, and the potential mechanism of exercise-induced mitochondrial biogenesis via Rev-erbα are sorted out and discussed, which can provide theoretical references to the mechanism of exercise-promoted mitochondrial biogenesis.

Real-world setting comparison of bridging therapy versus direct mechanical thrombectomy for acute ischemic stroke: A meta-analysis

Abstract Background and purpose Intravenous Thrombolysis (IVT) prior to Mechanical Thrombectomy (MT) for Acute Ischaemic Stroke (AIS) due to Large-Vessel Occlusion (LVO) remains controversial. Therefore, the authors performed a meta-analysis of the available real-world evidence focusing on the efficacy and safety of Bridging Therapy (BT) compared with direct MT in patients with AIS due to LVO. Methods Four databases were searched until 01 February 2023. Retrospective and prospective studies from nationwide or health organization registry databases that compared the clinical outcomes of BT and direct MT were included. Odds Ratios (ORs) and 95 % Confidence Intervals (CIs) for efficacy and safety outcomes were pooled using a random-effects model. Results Of the 12 studies, 86,695 patients were included. In patients with AIS due to LVO, BT group was associated with higher odds of achieving excellent functional outcome (modified Rankin Scale score 0-1) at 90 days (OR = 1.48, 95 % CI 1.25-1.75), favorable discharge disposition (to the home with or without services) (OR = 1.33, 95 % CI 1.29-1.38), and decreased mortality at 90 days (OR = 0.62, 95 % CI 0.56-0.70), as compared with the direct MT group. In addition, the risk of symptomatic intracranial hemorrhage did not increase significantly in the BT group. Conclusion The present meta-analysis indicates that BT was associated with favorable outcomes in patients with AIS due to LVO. These findings support the current practice in a real-world setting and strengthen their validity. For patients eligible for both IVT and MT, BT remains the standard treatment until more data are available.

Developmental status of iron deficiency anemia and factors among preschool children in Dongguan / 中国学校卫生

Objective@#To analyze the influencing factors and physical and mental development of preschool children with iron deficiency anemia in Dongguan, so as to provide a reference for the prevention of iron deficiency anemia among preschool children.@*Methods@#A total of 118 preschool children with iron deficiency anemia who were examined in Dongguan Maternal and Child Health Center from January 2022 to December 2022 were enrolled in the anemia group, and 118 preschool healthy children who were examined in the hospital at the same time were enrolled in the control group. The physical and mental development of the children were evalucded in both groups. Demographic information and household per capita income were collected. The relationship between risk factors and iron deficiency anemia was analyzed by univariate analysis and multiple Logistic regression.@*Results@#The scores of fine motor skills, gross motor skills, adaptability, social communication, language ability and developmental quotient of children in anemia group were significantly lower than those in control group ( t =4.14, 5.46, 5.60, 5.50, 4.90, 5.83, P <0.01). The difference in scores of adaptability, fine motor skills, gross motor skills language ability, social communication and developmental quotient between the two groups increased with age ( F =390.56, 414.63, 437.35, 409.68, 407.20, 404.54, P < 0.05 ). Multivariate Logistic regression analysis showed that household income, history of past digestive disease, gestational age, maternal anemia during pregnancy, maternal education, consumption of meat, eggs and milk, and intake of nuts were all associated with iron deficiency anemia among preschool children in Dongguan ( OR =2.23，2.99，3.99，3.56，3.11，1.68，1.61, P < 0.05 ).@*Conclusion@#The physical and mental development of preschool children with iron deficiency anemia in Dongguan is slower than that of non anemia children of the same age, and the development delay becomes more obvious with increasing age. Attention should be paid to the prevention of iron deficiency anemia among preschool children. It is important to provide reasonable dietary guidance for children with high risk factors such as digestive disease history and prematurity.

Management and prognosis of extremely preterm infants with gestational age ≤25+6 weeks / 中华儿科杂志

Objective: To investigate the outcomes including major complications and prognosis of extremely preterm infants with gestational age ≤25+6 weeks. Methods: The cross-sectional study enrolled 233 extremely preterm infants with gestational age ≤25+6 weeks who were admitted to the Department of Neonatology of Shenzhen Maternity and Child Healthcare Hospital from January 2015 to December 2021. The clinical data including perinatal factors, treatments, complications, and prognosis were extracted and analyzed. These extremely preterm infants were also grouped according to gestational age and year of admission to further analyze their survival rate, major complications, causes of death, and long-term outcomes. The comparisons between the groups were performed with Chi-square test and Kruskal-Wallis. Results: Among these 233 extremely preterm infants, 134 (57.5%) were males and 99 (42.5%) females. The gestational age was (24.6±0.9) weeks, the birth weight was 710.0 (605.0,784.5) g, and the overall survival rate was 61.8% (144/233). Among the surviving extremely preterm infants, the earliest gestational age was 22+2 weeks and the lowest birth weight was 390 g. There were 17.6% (41/233) of extremely preterm infants had treatment withdrawn and were discharged in line with the will of guardians. Among the rest 192 extremely preterm infants managed with aggressive treatments, 14 (7.3%) died in hospital and 34 (17.7%) had treatment withdrawn later due to severe complications. Of the 192 extremely preterm infants, 144 (75.0%) survived, and the survival rate increased year by year (χ2=26.28, P<0.001) while the mortality decreased year by year (χ2=14.09, P=0.027). Among the survivors, 20.8%(30/144) had no major complications, and the incidence of complications was also negatively related with the gestational age (χ2=7.24, P=0.044), and the length of invasive ventilation was negatively related to the gestational age (χ2=29.14, P<0.001). In the group of less than 23+6 weeks, all extremely preterm infants had one or more major complications. The follow-up were completed in 122 infants and revealed that delayed motor development, language retardation, and hearing and vision impairment accounted for 17.2% (21/122), 8.2% (10/122) and 17.2% (21/122), respectively. Conclusions: Extremely preterm infants with gestational age ≤25+6 weeks are difficult to treat, but the survival rate of infants undergoing aggressive treatments increases year by year. Although the prevalence of major complications is still high, most extremely preterm infants have acceptable prognosis during follow-up.

Stigmasterol protects human brain microvessel endothelial cells against ischemia-reperfusion injury through suppressing EPHA2 phosphorylation / 中国天然药物

Stigmasterol is a plant sterol with anti-apoptotic, anti-oxidative and anti-inflammatory effect through multiple mechanisms. In this study, we further assessed whether it exerts protective effect on human brain microvessel endothelial cells (HBMECs) against ischemia-reperfusion injury and explored the underlying mechanisms. HBMECs were used to establish an in vitro oxygen and glucose deprivation/reperfusion (OGD/R) model, while a middle cerebral artery occlusion (MCAO) model of rats were constructed. The interaction between stigmasterol and EPHA2 was detected by surface plasmon resonance (SPR) and cellular thermal shift assay (CETSA). The results showed that 10 μmol·L-1 stigmasterol significantly protected cell viability, alleviated the loss of tight junction proteins and attenuated the blood-brain barrier (BBB) damage induced by OGD/R in thein vitro model. Subsequent molecular docking showed that stigmasterol might interact with EPHA2 at multiple sites, including T692, a critical gatekeep residue of this receptor. Exogenous ephrin-A1 (an EPHA2 ligand) exacerbated OGD/R-induced EPHA2 phosphorylation at S897, facilitated ZO-1/claudin-5 loss, and promoted BBB leakage in vitro, which were significantly attenuated after stigmasterol treatment. The rat MCAO model confirmed these protective effects in vivo. In summary, these findings suggest that stigmasterol protects HBMECs against ischemia-reperfusion injury by maintaining cell viability, reducing the loss of tight junction proteins, and attenuating the BBB damage. These protective effects are at least meditated by its interaction with EPHA2 and inhibitory effect on EPHA2 phosphorylation.

Whole-course management strategies for gastroesophageal reflux disease: an evidence mapping study based on clinical practice guidelines / 中华胃肠外科杂志

Gastroesophageal reflux disease (GERD) is one of the most common digestive diseases with high incidence, complicated clinical symptoms, difficulties in standard treatment, and heavy medical burden. At present, some GERD-relevant clinical practice guidelines (CPGs) have been issued by different countries and academic organizations, but some recommendations were inconsistent, which has caused some problems for the current clinical whole-course management of GERD. To summarize the relevant evidence among the CPGs on GERD and formulate the whole- course management strategies, we included GERD-relevant CPGs published or updated after 2010 by searching websites of guidelines, relevant professional societies, and electronic databases. We extracted the recommendations and summarized the evidence from the aspects of symptoms, epidemiology, diagnosis and treatment, which was presented in the form of evidence mapping. We included 24 CPGs, including three in Chinese and 21 in English. The clinical practice management strategies of GERD were formulated based on the evidence from the aspects of clinical symptoms, diagnostic methods, medical treatment, anti-reflux surgery and endoscopic treatment, psychological treatment, and traditional Chinese medicine treatment.

Research Progress on Regulatory Role of CircPVT1 in Tumors / 肿瘤防治研究

Circular RNA (circRNA) is involved in tumor progression. CircPVT1 is an oncogene that is abnormally expressed and correlated with a variety of tumors. It can regulate tumors' malignant behavior and affect the survival and prognosis of patients. This article reviews research on the regulatory roles of circPVT1 in tumors to provide references for accurate treatment.

Medical-electrical cross-case teaching and its teaching practice under the background of medical-industrial integration / 中华医学教育探索杂志

This paper introduces the teaching method of medical-electrical cross-integration and the teaching practice experience in the past three years by taking the integration of medicine and electrical engineering as an example. Starting from the analysis of the characteristics of learning situation, the teaching introduction process, the case discussion and analysis, and the after-class tracking and improvement, this paper analyzes the characteristics of the medical-electrical cross-teaching and proposes the corresponding teaching methods and supporting cases. Preliminary exploration attempts show that this teaching method can improve students' comprehensive ability, especially multidisciplinary thinking ability, and has a certain positive effect.

Analysis of survival time and benefits of postoperative radiotherapy in resected small cell lung cancer patients / 中华放射肿瘤学杂志

Objective:To analyze the survival time, prognostic factors and the value of postoperative thoracic radiotherapy in resected small cell lung cancer (SCLC) patients.Methods:Clinic opathological data of SCLC patients who received surgical treatment in Cancer Hospital & General Hospital of Ningxia Medical University from April 2014 to September 2021 were enrolled in this retrospective study. All patients were subject to follow-up. The survival time of SCLC patients was evaluated by Kaplan-Meier method. Univariate and multivariate analyses of prognostic factors were performed by Cox proportional hazard model.Results:A total of 64 patients with SCLC were enrolled in the study. The 5-year overall survival (OS) rate was 43.5%. Univariate analysis showed that TNM staging ( P=0.027), postoperative neutrophil-lymphocyte ratio (NLR) ( P=0.039) and adjuvant thoracic radiotherapy ( P=0.041) were the prognostic factors. Multivariate analysis showed that TNM staging ( P=0.038) and adjuvant thoracic radiotherapy ( P=0.022) were the prognostic factors in patients with SCLC. The 5-year OS rates of patients with and without adjuvant thoracic radiotherapy were 71.6% and 35.4% ( P=0.028), respectively. There was a statistically significant difference in the 5-year OS rates between pathological stage N 2 SCLC patients with or without adjuvant thoracic radiotherapy (75.0% vs. 0%, P=0.030). Conclusions:TNM staging and postoperative adjuvant thoracic radiotherapy are prognostic factors in patients with SCLC undergoing surgical treatment. Pathological stage N 2 SCLC patients can benefit from adjuvant thoracic radiotherapy.

Cloning and expression analysis of ANR genes from different species of Lonicera japonica Thunb / 药学学报

Anthocyanidin reductase (ANR) is one of the key enzyme in the flavonoid biosynthetic pathway, and its catalytic activity is important for the synthesis of plant anthocyanin. In this study, specific primers were designed according to the transcriptome data of Lonicera japonica Thunb., and the CDS, gDNA and promoter sequences of ANR genes from Lonicera japonica Thunb. and Lonicera japonica Thunb. var. chinensis (Wats.) Bak. were cloned. The results showed that the CDS sequences of LjANR and rLjANR were 1 002 bp, the gDNA sequences were 2 017 and 2 026 bp respectively, and the promoter sequences were 1 170 and 1 164 bp respectively. LjANR and rLjANR both contain 6 exons and 5 introns, which have the same length of exons and large differences in introns. The promoter sequences both contain a large number of light response, hormone response and abiotic stress response elements. Bioinformatics analysis showed that both LjANR and rLjANR encoded 333 amino acids and were predicted to be stable hydrophobic proteins without transmembrane segments and signal peptides. The secondary structures of LjANR and rLjANR were predicted to be mainly consisted of α-helix and random coil. Sequence alignment and phylogenetic analysis showed that LjANR and rLjANR had high homology with Actinidia chinensis var. chinensis, Camellia sinensis and Camellia oleifera, and were closely related to them. The expression levels of LjANR and rLjANR were the highest in flower buds and the lowest in roots. The expression patterns at different flowering stages were similar, with higher expression levels in S1 and S2 stages and then gradually decreased until reaching the lowest level in S4 stage, after a slow increase in S5 stage, the expression levels decreased again. The expression levels of ANR genes in the two varieties showed significant differences in roots, S2 and S5 stages, while the differences in stems, flower buds, S1, S3 and S6 stages were extremely significant. The prokaryotic expression vector pET-32a-LjANR was constructed for protein expression. The target protein was successfully expressed of about 59 kD. This study lays a foundation for further study on the function of ANR gene and provides theoretical guidance for breeding new varieties of Lonicera japonica Thunb.

Titin: structure, isoforms and functional regulation / 生理学报

Titin, the largest known protein in the body expressed in three isoforms (N2A, N2BA and N2B), is essential for muscle structure, force generation, conduction and regulation. Since the 1950s, muscle contraction mechanisms have been explained by the sliding filament theory involving thin and thick muscle filaments, while the contribution of cytoskeleton in force generation and conduction was ignored. With the discovery of insoluble protein residues and large molecular weight proteins in muscle fibers, the third myofilament, titin, has been identified and attracted a lot of interests. The development of single molecule mechanics and gene sequencing technology further contributed to the extensive studies on the arrangement, structure, elastic properties and components of titin in sarcomere. Therefore, this paper reviews the structure, isforms classification, elastic function and regulatory factors of titin, to provide better understanding of titin.

Low XIST expression in Sertoli cells of Klinefelter syndrome patients causes high susceptibility of these cells to an extra X chromosome / 亚洲男科学杂志(英文版)

Klinefelter syndrome (KS) is the most common genetic cause of human male infertility. However, the effect of the extra X chromosome on different testicular cell types remains poorly understood. Here, we profiled testicular single-cell transcriptomes from three KS patients and normal karyotype control individuals. Among the different somatic cells, Sertoli cells showed the greatest transcriptome changes in KS patients. Further analysis showed that X-inactive-specific transcript ( XIST ), a key factor that inactivates one X chromosome in female mammals, was widely expressed in each testicular somatic cell type but not in Sertoli cells. The loss of XIST in Sertoli cells leads to an increased level of X chromosome genes, and further disrupts their transcription pattern and cellular function. This phenomenon was not detected in other somatic cells such as Leydig cells and vascular endothelial cells. These results proposed a new mechanism to explain why testicular atrophy in KS patients is heterogeneous with loss of seminiferous tubules but interstitial hyperplasia. Our study provides a theoretical basis for subsequent research and related treatment of KS by identifying Sertoli cell-specific X chromosome inactivation failure.

scRNA-seq reveals that origin recognition complex subunit 6 regulates mouse spermatogonial cell proliferation and apoptosis via activation of Wnt/β-catenin signaling / 亚洲男科学杂志(英文版)

The regulation of spermatogonial proliferation and apoptosis is of great significance for maintaining spermatogenesis. The single-cell RNA sequencing (scRNA-seq) analysis of the testis was performed to identify genes upregulated in spermatogonia. Using scRNA-seq analysis, we identified the spermatogonia upregulated gene origin recognition complex subunit 6 (Orc6), which is involved in DNA replication and cell cycle regulation; its protein expression in the human and mouse testis was detected by western blot and immunofluorescence. To explore the potential function of Orc6 in spermatogonia, the C18-4 cell line was transfected with control or Orc6 siRNA. Subsequently, 5-ethynyl-2-deoxyuridine (EdU) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays, flow cytometry, and western blot were used to evaluate its effects on proliferation and apoptosis. It was revealed that ORC6 could promote proliferation and inhibit apoptosis of C18-4 cells. Bulk RNA sequencing and bioinformatics analysis indicated that Orc6 was involved in the activation of wingless/integrated (Wnt)/ β-catenin signaling. Western blot revealed that the expression of β-catenin protein and its phosphorylation (Ser675) were significantly decreased when silencing the expression of ORC6. Our findings indicated that Orc6 was upregulated in spermatogonia, whereby it regulated proliferation and apoptosis by activating Wnt/β-catenin signaling.

Effects of Compound Danshen Dripping Pills on Ventricular Remodeling and Cardiac Function after Acute Anterior Wall ST-Segment Elevation Myocardial Infarction (CODE-AAMI): Protocol for a Randomized Placebo-Controlled Trial / 中国结合医学杂志

BACKGROUND@#Ventricular remodeling after acute anterior wall ST-segment elevation myocardial infarction (AAMI) is an important factor in occurrence of heart failure which additionally results in poor prognosis. Therefore, the treatment of ventricular remodeling needs to be further optimized. Compound Danshen Dripping Pills (CDDP), a traditional Chinese medicine, exerts a protective effect on microcirculatory disturbance caused by ischemia-reperfusion injury and attenuates ventricular remodeling after myocardial infarction.@*OBJECTIVE@#This study is designed to evaluate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function after AAMI on a larger scale.@*METHODS@#This study is a multi-center, randomized, double-blind, placebo-controlled, parallel-group clinical trial. The total of 268 patients with AAMI after primary percutaneous coronary intervention (pPCI) will be randomly assigned 1:1 to the CDDP group (n=134) and control group (n=134) with a follow-up of 48 weeks. Both groups will be treated with standard therapy of ST-segment elevation myocardial infarction (STEMI), with the CDDP group administrating 20 tablets of CDDP before pPCI and 10 tablets 3 times daily after pPCI, and the control group treated with a placebo simultaneously. The primary endpoint is 48-week echocardiographic outcomes including left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume index (LVEDVI), and left ventricular end-systolic volume index (LVESVI). The secondary endpoint includes the change in N terminal pro-B-type natriuretic peptide (NT-proBNP) level, arrhythmias, and cardiovascular events (death, cardiac arrest, or cardiopulmonary resuscitation, rehospitalization due to heart failure or angina pectoris, deterioration of cardiac function, and stroke). Investigators and patients are both blinded to the allocated treatment.@*DISCUSSION@#This prospective study will investigate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function in patients undergoing pPCI for a first AAMI. Patients in the CDDP group will be compared with those in the control group. If certified to be effective, CDDP treatment in AAMI will probably be advised on a larger scale. (Trial registration No. NCT05000411).

Efficacy of CLAE Chemotherapy Regimen Followed by Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Relapsed/Refractory Acute Leukemia / 中国实验血液学杂志

OBJECTIVE@#To observe the efficacy and safety of CLAE intensive chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with relapsed/refractory acute leukemia (R/R AL).@*METHODS@#CLAE regimen [cladribine 5 mg/(m2·d), d 1-5; cytarabine 1.5 g/(m2·d), d 1-5; etoposide 100 mg/(m2·d), d 3-5] followed by allo-HSCT was used to treat 3 R/R AL patients. The patients received CLAE chemotherapy in relapsed or refractory status and underwent bone marrow puncture to judge myelodysplastic state. After an interval of 3 to 5 days, followed by preconditioning regimen for allo-HSCT [fludarabine 30 mg/(m2·d), d -7 to d -3; busulfan 0.8 mg/kg q6h, d -6 to d -3 or d -5 to d -2. If the bone marrow hyperplasia was not active and the blasts were less than 10%, busulfan should be used for 3 days. If the bone marrow hyperplasia was active and the blasts were more than 10%, busulfan should be used for 4 days]. Cyclosporin A, mycophenolate mofetil and short-term methotrexate were used for graft-versus-host disease (GVHD) prevention. After transplantation, the status of minimal residual disease (MRD) and bone marrow chimerism were regularly monitored in all 3 patients, and demethylation drugs or dasatinib were used to prevent recurrence 3 months after transplantation.@*RESULTS@#2 patients with t(11;19) translocation and relapse/refractory acute myeloid leukemia recurred within 6 months after induction of remission, and received intensive chemotherapy with CLAE regimen followed by haploidentical allo-HSCT and unrelated donor allo-HSCT, respectively. The two patients both relapsed 6 months after transplantation, then achieved complete remission by donor lymphocyte infusion, interferon, interleukin-2 and other methods, and disease-free survival was 2 years after transplantation. The other patient was chronic myelogenous leukemia who developed acute lymphoblastic leukemia during oral administration of tyrosine kinase inhibitor, accompanied by T315I and E255K mutations in ABL1 kinase region and additional chromosomal abnormalities. After morphological remission by induction chemotherapy, central nervous system leukemia was complicated. Intensive chemotherapy with CLAE regimen followed by sibling allo-HSCT was performed in the positive state of MRD. The patient relapsed 3 months after transplantation, and achieved remission after chimeric antigen receptor T-cell (CAR-T) therapy, however, he died 5 months after transplantation because of severe cytokine release syndrome (CRS) and GVHD.@*CONCLUSION@#CLAE regimen followed by allo-HSCT may be an effective salvage treatment option for R/R AL patients to prolong the overall survival.

Feasibility and clinical benefits of the double-ProGlide technique for hemostasis after cryoballoon atrial fibrillation ablation with uninterrupted oral anticoagulants / 老年心脏病学杂志（英文版）

OBJECTIVE@#To access the efficacy and safety of the double-ProGlide technique for the femoral vein access-site closure in cryoballoon ablation with uninterrupted oral anticoagulants (OAC), and its impact on the electrophysiology laboratory time as well as hospital stay after the procedure in this observational study.@*METHODS@#Patients with atrial fibrillation undergoing cryoballoon ablation with uninterrupted OAC at Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China from May 2019 to May 2021 were enrolled in this study. From October 2020, double-ProGlide technique was consistently used for hemostasis (ProGlide group), and before that conventional manual compression was utilized (manual compression group). The occurrence of vascular and groin complications was accessed during the hospital stay and until the three-month follow-up.@*RESULTS@#A total of 140 participants (69.30% of male, mean age: 59.21 ± 10.29 years) were evaluated, 70 participants being in each group. Immediate hemostasis was achieved in all the patients with ProGlide closure. No major vascular complications were found in the ProGlide group while two major vascular complications were occurred in the manual compression group. The incidence of any groin complication was obviously higher in subjects with manual compression than patients with ProGlide devices (15.71% vs. 2.86%, P = 0.009). In addition, compared with the manual compression group, the ProGlide group was associated with significantly shorter total time in the electrophysiology laboratory [112.0 (93.3-128.8) min vs. 123.5 (107.3-158.3) min, P = 0.006], time from sheath removal until venous site hemostasis [3.8 (3.4-4.2) min vs. 8.0 (7.6-8.5) min, P < 0.001], bed rest time [8.0 (7.6-8.0) h vs. 14.1 (12.0-17.6) h, P < 0.001] and hospital stay after the procedure [13.8 (12.5-17.8) h vs. 38.0 (21.5-41.0) h, P < 0.001].@*CONCLUSIONS@#Utilization of the double-ProGlide technique for hemostasis after cryoballoon ablation with uninterrupted OAC is feasible and safe, which has the clinical benefit in reducing the total electrophysiology laboratory time and the hospital stay length after the procedure.