[Clinical Characteristics and Prognosis of Acute Myeloid Leukemia Patients with GATA2 Gene Mutation].

OBJECTIVE: To investigate the clinical characteristics, coexisting gene mutations and prognosis of acute myeloid leukemia (AML) patients with GATA2 gene mutation. METHODS: The clinical data of 370 newly diagnosed AML patients treated in our hospital from January 2008 to January 2021 was analyzed retrospectively, the next-generation sequencing technology was used to detect the mutated genes in those patients. The clinical characteristics of AML patients with GATA2 mutations, the co-mutated genes of GATA2 mutations, and the effect of GATA2 mutation on prognosis were analyzed. RESULTS: A total of 23 patients (6.2%) with GATA2 mutation was detected in 370 AML patients. Compared with GATA2 non-mutation group, patients in GATA2 mutation group were mostly normal karyotypes (P =0.037) and in low-risk cytogenetic stratification (P =0.028). The incidence of CEBPAdm and NRAS in GATA2 mutation group was significantly higher than that in GATA2 non-mutation group (P =0.010, P =0.009). There were no statistically significant differences between the two groups in terms of sex, age, white blood cell count (WBC), platelet count, hemoglobin, bone marrow (BM) blast, induction chemotherapy regimen and CR rate (P >0.05). Among the 23 patients with GATA2 mutation, the most common co-mutated genes were CEBPAdm, NRAS (both 39.1%), NPM1, FLT3, TET2, WT1 (all 17.4%), ASXL1 and IDH1 (both 13.0%). Survival analysis showed that there was no statistical difference in 5-year overall survival (OS) and leukemia-free survival (LFS) rates between patients with and without GATA2 mutations in whole cohort (n=370) (P =0.306, P =0.308). Among 306 patients without CEBPAdm, the 5-year OS and LFS rates in GATA2 mutation group showed an increasing trend compared with GATA2 non-mutation group, but the difference was not statistically significant (P =0.092, P =0.056). Among 64 patients with CEBPAdm, there was no statistically significant difference in 5-year OS rate between the GATA2 mutation group and the GATA2 non-mutation group (P =0.104), but the 5-year LFS rate of the GATA2 mutation group was significantly decreased (P =0.047). Among the 23 patients with GATA2 mutation, 16 cases received the "3+7" induction regimen, of which 12 cases received allogeneic hematopoietic stem cell transplantation (allo-HSCT); 7 cases received the "DCAG" induction regimen, of which 3 cases received allo-HSCT. The CR rate was not statistically different between the "3+7" regimen group and the "DCAG" regimen group (P =1.000). The 5-year OS rate and LFS rate in the transplantation group were significantly higher than the chemotherapy group (P =0.021, P =0.020). CONCLUSION: GATA2 mutation is more common in AML patients with normal karyotype and low-risk cytogenetic stratification, and it is significantly associated with CEBPAdm and NRAS co-mutations. The prognostic significance of GATA2 is influenced by CEBPAdm. The choice of "3+7" or "DCAG" induction regimen in patients with GATA2 mutation does not affect their CR rate, while the choice of allo-HSCT can significantly improved the prognosis compared with chemotherapy only.

Case Report: ECMO-assisted tracheal reconstruction in a 30-week-gestation preterm infant with tracheal stenosis.

Tracheal stenosis is a rare but life-threatening disease in preterm infants. Misdiagnosis as congenital tracheal stenosis is common, making surgical management challenging. This report presents a case of a preterm infant with tracheal stenosis and congenital heart malformation treated with ECMO-assisted tracheal resection and end-to-end anastomosis. A male infant was born at 30 weeks of gestation with severe asphyxia, cardiac insufficiency, and pneumonia. Following failed medical treatment, fiberoptic bronchoscopy confirmed mid-tracheal to carinal stenosis. After a 2-week treatment course, ECMO-assisted tracheal resection and end-to-end anastomosis were performed successfully. This case confirms the feasibility of tracheal resection and end-to-end anastomosis in low-weight, preterm infants with tracheal stenosis born at 30 weeks gestation. The utilization of ECMO for oxygenation during surgery provides a clear surgical field and shorter operating time. Surgical intervention may be necessary for neonatal tracheal stenosis depending on the clinical presentation.

Revisiting Waist Circumference: A Hypertension Risk Factor that Requires a More In-depth Understanding.

As a major cause of various cardiovascular diseases, the prevalence of hypertension has been increasing in the past 30 years, leading to significant socioeconomic and health burdens. Obesity is one of the major risk factors for hypertension. Body mass index (BMI) is the most used anthropometric index to measure obesity in clinical practice and to assess the risk of obesity-related diseases. However, obesity is a heterogeneous disease, and the accumulation of fat in different body regions leads to differences in cardiovascular and metabolic risks. BMI only reflects the overall obesity but does not consider the distribution of fat and muscle mass. The limitation of BMI makes it insufficient to assess the risk of hypertension attributed to obesity. In addition, waist circumference is an easily obtainable anthropometric index to evaluate abdominal fat distribution. High waist circumference is an independent risk factor for various cardiovascular diseases and all-cause mortality regardless of BMI. Preliminary data indicate that waist circumference is significantly associated with the risk of hypertension at different BMI levels. However, routine measurement of waist circumference is currently not required in current clinical guidelines or is only recommended for obese populations, indicating an insufficient understanding of waist circumference. In this review, we summarize the measurement methods and diagnostic thresholds of waist circumference for abdominal obesity, the trend of central obesity prevalence, the superiority of waist circumference over other anthropometric indices, and recent cross-sectional and longitudinal studies on the association between obesity and hypertension.

Rapid screening of point mutations by mismatch amplification mutation assay PCR.

Metabolic engineering frequently makes use of point mutation and saturation mutation library creation. At present, sequencing is the only reliable and direct technique to detect point mutation and screen saturation mutation library. In this study, mismatch amplification mutation assay (MAMA) PCR was used to detect point mutation and screen saturation mutation library. In order to fine-tune the expression of odhA encoding 2-oxoglutarate dehydrogenase E1 component, a saturating mutant library of the RBS of odhA was created in Corynebacterium glutamicum P12 based on the CRISPR-Cas2a genome editing system, which increased the L-proline production by 81.3%. MAMA PCR was used to filter out 42% of the non-mutant transformants in the mutant library, which effectively reduced the workload of the subsequent fermentation test and the number of sequenced samples. The rapid and sensitive MAMA-PCR method established in this study provides a general strategy for detecting point mutations and improving the efficiency of mutation library screening. KEY POINTS: • MAMA PCR was optimized and developed to detect point mutation. • MAMA PCR greatly improves the screening efficiency of point mutation. • Attenuation of odhA expression in P12 effectively improves proline production.

Application of neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy in curative surgery for esophageal cancer: A meta-analysis.

BACKGROUND: The effectiveness of neoadjuvant therapy in esophageal cancer (EC) treatment is still a subject of debate. AIM: To compare the clinical efficacy and toxic side effects between neoadjuvant chemoradiotherapy (nCRT) and neoadjuvant chemotherapy (nCT) for locally advanced EC (LAEC). METHODS: A comprehensive search was conducted using multiple databases, including PubMed, EMBASE, MEDLINE, Science Direct, The Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, Chinese Science and Technology Journal Database, and Chinese Biomedical Literature Database Article. Studies up to December 2022 comparing nCRT and nCT in patients with EC were selected. RESULTS: The analysis revealed significant differences between nCRT and nCT in terms of disease-free survival. The results indicated that nCRT provided better outcomes in terms of the 3-year overall survival rate (OSR) [odds ratio (OR) = 0.95], complete response rate (OR = 3.15), and R0 clearance rate (CR) (OR = 2.25). However, nCT demonstrated a better 5-year OSR (OR = 1.02) than nCRT. Moreover, when compared to nCRT, nCT showed reduced risks of cardiac complications (OR = 1.15) and pulmonary complications (OR = 1.30). CONCLUSION: Overall, both nCRT and nCT were effective in terms of survival outcomes for LAEC. However, nCT exhibited better performance in terms of postoperative complications.

Ratio of waist circumference to body mass index: A novel predictor of clinical outcome in hypertension patients.

We aim to investigate the influence of waist circumference and body mass index (BMI) on all-cause death and cardiovascular-specific death in patients with hypertension. This prospective cohort study, based on waist circumference and body mass index measurements in patients with hypertension, provided risk estimates of all-cause mortality and cardiovascular events. The waist circumference-to-BMI ratio (WtBR) is an anthropometric measure integrating waist circumference and BMI. We utilized multivariable Cox regression analysis, restricted cubic spline model, Kaplan-Meier plot, random forest analysis, and sensitivity analysis to assess the relationship of WtBR with all-cause mortality. Subsequently, Fine-Gray competing risk regression models were applied to precisely evaluate the probability of cardiovascular-specific death attributed to high WtBR. The results indicate that thea deceased group showed significantly higher WtBR and lower BMI compared with the alive groups (P < .05), while no significant difference was observed in waist circumference (P = .373). When analyzed as continuous, the risk of all-cause death elevated with increasing WtBR in the adjusted model with an HR of 2.42 (95% CI, 2.06-2.85). The restricted cubic spline illustrated an elevated risk of all-cause mortality as WtBR increased (J-shaped curve). Nevertheless, WtBR showed no significant association with cardiovascular-specific death and the prediction model exhibited a reliable performance in the testing set. This study supported that WtBR, an anthropometric measure, is independently associated with all-cause death in hypertensive patients. It's advisable to routinely assess waist circumference in hypertensive patients regardless of BMI, in order to more effectively manage the risk of obesity-related health.

Effect and Mechanism of Chinese Medicine in Treatment of Osteoporosis / 中国实验方剂学杂志

Osteoporosis （OP） is a common bone disease affecting the quality of life and causing huge medical burden to the patients and society. The occurrence of OP is mainly caused by excessive bone resorption and insufficient bone formation， which are directly influenced by external calcium ion balance. Calcium imbalance can impair bone integrity， reduce the calcium supply to the bone， and lower the calcium content in the bone， thus triggering OP. Drugs are the main anti-OP therapy in modern medicine， which， however， may cause adverse reactions and drug dependence. Chinese medicines have good clinical effects and high safety in treating OP， being suitable for long-term use. Recent studies have shown that Chinese medicines can alleviate estrogen deficiency， regulate bone cell and calcium metabolism， which is crucial for the formation and development of OP. The transient receptor potential cation channel superfamily V members 5 and 6 （TRPV5 and TRPV6， respectively） affect bone homeostasis by mediating the transmembrane calcium ion transport in the intestine （TRPV6） and kidney （TRPV5）. Therefore， TRPV5/6 is one of the key targets to understand the anti-OP mechanisms of the effective parts of Chinese medicines， which is worthy of further study. This paper summarizes the research results about the anti-OP effects of Chinese medicines in the last two decades， especially the mechanism of regulating calcium metabolism， aiming to provide new ideas for the basic research， clinical application， and drug development of OP treatment.

Water isolation technique combined with contrast-enhanced ultrasound guided puncture biopsy of pancreatic mass in 3 cases.

In many patients with pancreatic cancer the definite pathological diagnosis is limited due to the lack of safe needle entry routes, the high risk of conventional ultrasound-guided puncture and the low positive rate of single needle. To solve the situations in which there are no safe path for pancreatic biopsy, we used water isolation technology combined with contrast-enhanced ultrasound to perform puncture biopsy in 3 patients with pancreatic mass occupying under the guidance of coaxial needle in this study and remarkable results were achieved. The water isolation technique was used to avoid the damage to theimportant organs in front of the occupying area.

A dose-escalation study of HP501, a highly selective URAT1 inhibitor, in male Chinese patients with hyperuricemia.

HP501 is a highly selective renal urate transporter 1 (URAT1) inhibitor used for treating hyperuricemia. This study aimed to evaluate the tolerability, pharmacokinetics, and pharmacodynamics of HP501 in male Chinese patients. Patients with hyperuricemia were sequentially assigned to receive oral doses of HP501 (30, 50, 60, 90, and 120 mg) as a single dose on Day 1 and as once-daily doses from Days 4 to 13. Safety, pharmacokinetic, and pharmacodynamic data were collected. Multiple oral doses of HP501 were well-tolerated in all the cohorts. The most common adverse events (≥ 10% of patients) of any grade regardless of drug relationship were gout flare (14 patients, 25.93%), diarrhea (12 patients, 22.22%), elevated ALT (8 patients, 14.81%), hypertriglyceridemia (7 patients, 12.96%), dry mouth (7 patients, 12.96%) and oral ulcer (7 patients, 12.96%). All adverse events were mild or moderate. The Cmax and exposure (AUC) of HP501 was approximately dose-proportional between 30 and 120 mg. A dose-dependent serum uric acid (UA)-lowering effect was observed in the dose range of 30 to 60 mg and the serum UA lowering effect was similar between 90 and 120 mg on day 13, indicating that the maximal serum UA lowering effect of HP501 was achieved at 90 mg in the patients with hyperuricemia. In conclusion, the tolerability, pharmacokinetics, and pharmacodynamics supported 90 mg HP501 for subsequent clinical studies of this highly selective URAT1 inhibitor.Clinical Trial registration: No. CTR20212259 ( http://www.chinadrugtrials.org.cn/ ) was registered in September 2021, and No. CTR20222257 was registered in September 2022.

Maternal dominance contributes to subgenome differentiation in allopolyploid fishes.

Teleost fishes, which are the largest and most diverse group of living vertebrates, have a rich history of ancient and recent polyploidy. Previous studies of allotetraploid common carp and goldfish (cyprinids) reported a dominant subgenome, which is more expressed and exhibits biased gene retention. However, the underlying mechanisms contributing to observed 'subgenome dominance' remains poorly understood. Here we report high-quality genomes of twenty-one cyprinids to investigate the origin and subsequent subgenome evolution patterns following three independent allopolyploidy events. We identify the closest extant relatives of the diploid progenitor species, investigate genetic and epigenetic differences among subgenomes, and conclude that observed subgenome dominance patterns are likely due to a combination of maternal dominance and transposable element densities in each polyploid. These findings provide an important foundation to understanding subgenome dominance patterns observed in teleost fishes, and ultimately the role of polyploidy in contributing to evolutionary innovations.

Conformal sphincteric resection for ultra-low rectal cancer located below the dentate line: A pilot report.

AIM: Sphincter-sparing surgery can be achieved in most cases of low rectal cancer with the development of intersphincteric resection. However, abdominoperineal resection is still inevitable for patients with tumours located below the dentate line. To address this, we have developed a procedure called conformal sphincteric resection (CSR) in which the corresponding part of the subcutaneous portion of the external anal sphincter and the perianal skin on the tumour side is removed to achieve a safe distal resection margin and lateral resection margin while the dentate line and the internal anal sphincter on the tumour-free side are preserved as much as possible, to achieve sphincter preservation without compromising oncological safety and functional acceptability, and to render tumour location no longer a contraindication for sphincter-sparing surgery. This is the first study to describe the concept, indication and surgical procedure of CSR and to report its preliminary surgical, oncological and functional results. METHODS: This is a retrospective, single-centre, single-arm pilot study conducted at Huashan Hospital, Fudan University. Demographic, clinicopathological, oncological and functional follow-up data were collected from 20 consecutive patients with rectal tumours located below the dentate line who underwent laparoscopic CSR by the same surgical team from June 2018 to March 2022. RESULTS: The mean distance of the tumour's lower edge from the anal verge was 13.1 ± 6.0 mm. The mean distal resection margin was 10.6 ± 4.3 mm. All circumferential resection margins were negative. There were no instances of perioperative mortality. The complication rate was 25% but all were Clavien-Dindo Grade I. Among the 20 cases, 17 were diagnosed with adenocarcinoma, one with squamous cell carcinoma and two with adenoma featuring high-grade intraepithelial neoplasia. Pathological TNM staging revealed two, seven, five, five and one case(s) in Stages 0, I, II, III and IV, respectively. The median follow-up period was 20 months (interquartile range 22 months), with no withdrawals. The overall and disease-free survival rates were both 95%. The mean Wexner incontinence score and low anterior resection syndrome score recorded 18 months following diverting ileostomy closure were 6.3 ± 3.8 and 27.3 ± 3.6, respectively. CONCLUSIONS: This study has proposed the CSR procedure for the first time, which is a technically feasible, oncologically safe and functionally acceptable procedure for carefully selected patients with rectal tumours located below the dentate line.

Case report: Uniportal video-assisted thoracoscopic sleeve lobectomy in a 6-year-old patient with inflammatory myofibroblastic tumor (IMT).

Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm that can occur in various organs, including the lung. Surgical resection is usually the preferred treatment for localized IMT.A 6-year-old female was admitted to our hospital with complaints of "coughing and vomiting for 6 days". A chest CT scan revealed occlusion of the left main bronchus, segmental atelectasis of the left lower lung, and cystic low-density shadows along the bronchial pathway. Subsequent fiberoptic bronchoscopy confirmed the diagnosis of IMT through pathological biopsy. After excluding surgical contraindications, the patient underwent uniportal video-assisted thoracoscopic sleeve lobectomy for treatment. The patient had an uneventful postoperative course and was discharged four days after surgery. After one month, the patient received a follow-up examination and reported no significant discomfort. A chest CT scan revealed no postoperative complications.Our experience suggests that uniportal video-assisted thoracoscopic surgery may be a safe and effective approach for the treatment of pediatric patients with IMT requiring complex surgical procedures such as sleeve lobectomy and tracheoplasty.

[Spectral Characteristics and Source Analysis of Chromophoric Dissolved Organic Matter in Surface Water of Taihu Lake Before Cyanobacterial Blooming].

Chromophoric dissolved organic matter (CDOM) is an important part of the nutrient biogeochemical cycle in aquatic ecosystems. To explore the characteristics and sources of CDOM components in the surface water of Taihu Lake, UV-visible spectroscopy and excitation emission matrix fluorescence spectroscopy-parallel factor analysis were used to analyze CDOM components in surface water. Combined with CDOM optical parameters (a355, SUVA254, a250/a365, FI, BIX, and HIX), the spatial differences and pollution sources were identified, and a preliminary comparison was made between this study and the historical data of CDOM components in Taihu Lake. According to the results, a355, SUVA254, and a250/a365 showed the characteristics of high concentration, high aromatic ability, and low relative molecular weight of CDOM in the surface water of the eastern part of Taihu Lake; however, the northern part showed the opposite characteristics. Four components were isolated from CDOM using parallel factor analysis:one tyrosine-like (C1), two types of tryptophan (C2 and C4), and one fulionic acid (C3). The main component C1 had a strong linear relationship with the C2 and C3 components, suggesting that different components originated from similar pollution sources. The fluorescence index showed that CDOM in different areas of Taihu Lake were differently affected by endogenous and terrestrial inputs; however, the overall humification degree was low. This indicated that the CDOM components in Taihu Lake were primarily protein-like (C1, C2, and C4) (>85%) and autogenous, with good biochemical availability.

Diagnostic Efficacy of 18F-FDG PET/CT in Detecting Bone Marrow Infiltration in Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma.

Objective: Diffuse large B-cell lymphoma (DLBCL) is often associated with bone marrow infiltration, and 2-deoxy-2-(18F) fluorodeoxyglucose positron emission tomography/computed tomography ( 18F-FDG PET/CT) has potential diagnostic significance for bone marrow infiltration in DLBCL. Methods: A total of 102 patients diagnosed with DLBCL between September 2019 and August 2022 were included. Bone marrow biopsy and 18F-FDG PET/CT examinations were performed at the time of initial diagnosis. Kappa tests were used to evaluate the agreement of 18F-FDG PET/CT with the gold standard, and the imaging features of DLBCL bone marrow infiltration on PET/CT were described. Results: The total detection rate of bone marrow infiltration was not significantly different between PET/CT and primary bone marrow biopsy ( P = 0.302) or between the two bone marrow biopsies ( P = 0.826). The sensitivity, specificity, and Youden index of PET/CT for the diagnosis of DLBCL bone marrow infiltration were 0.923 (95% CI, 0.759-0.979), 0.934 (95% CI, 0.855-0.972), and 0.857, respectively. Conclusion: 18F-FDG PET/CT has a comparable efficiency in the diagnosis of DLBCL bone marrow infiltration. PET/CT-guided bone marrow biopsy can reduce the misdiagnosis of DLBCL bone marrow infiltration.

Angiogenesis and flap-related research: A bibliometric analysis.

Adequate blood supply, a prerequisite for flap survival after grafting, makes angiogenesis of the flap the biggest problem to be solved. Researches have been conducted around vascularisation in correlation with flap grafting. However, bibliometric analyses systematically examining this research field are lacking. As such, we herein sought to conduct comprehensive comparative analyses of the contributions of different researchers, institutions, and countries to this research space in an effort to identify trends and hotspots in angiogenesis and vascularisation in the context of flap grafting. Publications pertaining to angiogenesis and vascularisation in the context of flap grafting were retrieved from the Web of Science Core Collection. References were then analysed and plotted using Microsoft Excel 2019, VOSviewer, and CiteSpace V. In total, 2234 papers that were cited 40 048 times (17.63 citations/paper) were included in this analysis. The greatest number of studies were from the United States, with these studies exhibiting both the highest number of citations (13 577) and the greatest overall H-index (60). For The institutions that published the greatest number of studies were WENZHOU MEDICAL UNIVERSITY (681), while UNIVERSITY OF ERLANGEN NUREMBERG has the highest number of citations (1458), and SHANGHAI JIAO TONG UNIVERSITY holds the greatest overall H-index (20). The greatest number of studies in this research space were published by Gao WY, while Horch RE was the most commonly cited researcher in the field. The VOS viewer software clustered relevant keywords into three clusters, with clusters 1, 2, 3, and 4 corresponding to studies in which the keywords 'anatomy', 'survival', 'transplantation', 'therapy' most frequently appeared. The most promising research hotspot-related terms in this field included 'autophagy', 'oxidative stress', 'ischemia/reperfusion injury', which exhibited a most recent average appearing year (AAY) of 2017 and after. Generally speaking, the results of this analysis indicate that the number of articles exploring angiogenesis and flap-related research has risen steadily, with the United States and China being the two countries publishing the greatest proportion of studies in this field. The overall focus of these studies has shifted away from 'infratest and tissue engineering' towards 'mechanisms'. In the future, particular attention should be paid to emerging research hotspots, which include 'ischemia/reperfusion injury' and treatments for promoting vascularization, such as 'platelet-rich plasma'. In light of these findings, funding agencies should continue increasing their investment in the exploration of the concrete mechanisms and interventional therapeutic relevance of angiogenesis during flap transplantation.

Prognostic value of TIMM50 expression in colorectal cancer.

Introduction: Translocase of the inner mitochondrial membrane 50 (TIMM50) is universally considered to play a key role in several malignancies. However, its role in predicting colorectal cancer (CRC) patient prognosis remains unclear. Material and methods: A total of 192 CRC patients (123 men and 69 women) who underwent radical resection participated in this study. The patients were followed up every 3 months after surgery for 5 years. TIMM50 expression in tumour tissues was measured by quantitative real-time PCR, Western blotting and immunohistochemistry. TIMM50 expression was studied to assess correlations with clinicopathological factors and survival time. Results: TIMM50 expression increased significantly in CRC tumour tissues. Moreover, high TIMM50 expression was related to pathologic stage (p = 0.043), N stage (p = 0.048) and distant metastasis (p = 0.015), but TIMM50 expression was not related to other clinical factors. A Kaplan-Meier survival analysis indicated that patients with low TIMM50 expression had a longer overall survival than those with high TIMM50 expression (p = 0.002). Furthermore, distant metastasis and high TIMM50 expression were confirmed as independent prognostic factors for the overall survival of CRC patients in a multivariate analysis (p = 0.003). Conclusions: TIMM50 may be a key factor for monitoring CRC and a new prognosis indicator for CRC patients.

Anti-apoptotic and anti-fibrotic efficacy of exercise training in hypertensive hearts: A systematic review.

Background: This review aims to summarize the antiapoptotic, pro-survival, and antifibrotic effects of exercise training in hypertensive hearts. Methods: Keyword searches were conducted in PubMed, Web of Science, and Scopus in May 2021. Research published in English on the effects of exercise training on the apoptosis, survival, and fibrosis pathways in hypertension was included. The CAMARADES checklist was used to determine the quality of the studies. Two reviewers independently implemented predesigned protocols for the search and selection of studies, the assessment of study quality, and the evaluation of the strength of evidence. Results: Eleven studies were included after selection. The duration of the exercise training ranged from 5 to 27 weeks. Nine studies showed that exercise training improved cardiac survival rates by increasing IGF-1, IGF-1 receptor, p-PI3K, Bcl-2, HSP 72, and p-Akt. Furthermore, 10 studies showed that exercise training reduced apoptotic pathways by downregulating Bid, t-Bid, Bad, Bak, Bax, TNF, and FADD. Finally, two studies reported the modification and subsequent improvement of physiological characteristics of fibrosis and decreased MAPK p38 and PTEN levels by exercise training in the left ventricle of the heart. Conclusions: The findings of the review showed that exercise training could improve cardiac survival rates and attenuate cardiac apoptotic and fibrotic pathways in hypertension, suggesting that exercise training could act as a therapeutic approach to prevent hypertension-induced cardiac apoptosis and fibrosis. Systematic Review Registration: https://www.crd.york.ac.uk, identifier: CRD42021254118.

Thorough research and modification of one-carbon units cycle for improving L-methionine production in Escherichia coli.

Methionine is the only one of the essential amino acids that contain sulfur, widely used as a feed additive in agriculture. In this study, the availability of 5-methyl-tetrahydrofolate was confirmed as the main limitation in the complex multibranched biosynthetic pathway of L-methionine. The cycle of one-carbon units was thoroughly investigated and modified to supply 5-methyl-tetrahydrofolate for L-methionine production, such as enhancing the supply of precursor, expediting the conversion rate of the cycle, introducing exogenous serine hydroxymethyltransferase and increasing pool size of one-carbon units carrier. The final strain MYA/pAmFA-4 was able to produce 20.89 g/L L-methionine by fed-batch fermentation, which was the highest titer reported in the literatures. This study is instructive for other metabolites biosynthesized needing one-carbon units or having a complex multibranched biosynthetic pathway. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03625-9.

Construction of exogenous methanol, formate, and betaine modules for methyl donor supply in methionine biosynthesis.

Methionine is an essential sulfur-containing amino acid that finds widespread applications in agriculture, medicine, and the food industry. However, the complex and multibranched biosynthetic pathway of methionine has posed significant challenges to its efficient fermentation production. In this study, we employed a modularized synthetic biology strategy to improve the weakest branched pathway of methionine biosynthesis. Three exogenous modules were constructed and assembled to provide methyl donors, which are the primary limiting factors in methionine biosynthesis. The first module utilized added methanol, which was converted into 5,10-methylene-tetrahydrofolate for methionine production but was hindered by the toxicity of methanol. To circumvent this issue, a non-toxic formate module was constructed, resulting in a visible improvement in the methionine titer. Finally, an exogenous betaine module was constructed, which could directly deliver methyl to methionine. The final strain produced 2.87 g/L of methionine in a flask, representing a 20% increase over the starting strain. This study presents a novel strategy for improving and balancing other metabolites that are synthesized through complex multibranched pathways.

Predicting the efficacy of high-intensity focused ultrasound (HIFU) ablation for uterine leiomyomas based on DTI indicators and imaging features.

PURPOSE: To predict the efficacy of high-intensity focused ultrasound (HIFU) ablation for uterine leiomyomas based on diffusion tensor imaging (DTI) indicators and imaging features. METHODS: Sixty-two patients with 85 uterine leiomyomas were consecutively enrolled in this retrospective study and underwent DTI scanning before HIFU treatment. Based on whether the non-perfused volume ratio (NPVR) was greater than 70%, all patients were assigned to sufficient ablation (NPVR ≥ 70%) or insufficient ablation (NPVR < 70%) groups. The selected DTI indicators and imaging features were incorporated to construct a combined model. The predictive performance of DTI indicators and the combined model were assessed using receiver operating characteristic (ROC) curves. RESULTS: There were 42 leiomyomas in the sufficient ablation group (NPVR ≥ 70%) and 43 leiomyomas in the insufficient ablation group (NPVR < 70%). The fractional anisotropy (FA) and relative anisotropy (RA) values were higher in the sufficient ablation group than in the insufficient ablation group (p < 0.05). Conversely, the volume ratio (VR) and mean diffusivity (MD) values were lower in the sufficient ablation group than those in the insufficient ablation group (p < 0.05). Notably, the combined model composed of the RA and enhancement degree values had high predictive efficiency, with an AUC of 0.915. The combined model demonstrated higher predictive performance than FA and MD alone (p = 0.032 and p < 0.001, respectively) but showed no significant improvement compared with RA and VR (p > 0.05). CONCLUSION: DTI indicators, especially the combined model incorporating DTI indicators and imaging features, can be a promising imaging tool to assist clinicians in predicting HIFU efficacy for uterine leiomyomas.