Serum dsDNA is environmentally contingent.

Psoriasis is a recurrent autoimmune disease characterized by seasonal and latitudinal variations. Double-stranded DNA (dsDNA) is a crucial component of nucleic acids and nucleosomes that provoke innate immune responses. Given the potential influence of climate on immunity and the development of autoimmune diseases, a comprehensive quantitative analysis of dsDNA levels in the population is warranted. In this case-control study conducted from 2016 to 2020, 10,110 psoriasis patients and matched controls from 12 regions in China were included. This study examined variations in serum dsDNA levels based on season and latitude. The results revealed significant associations between geographical location, climatic conditions, and season with serum dsDNA concentration. Individuals residing in Northern China exhibited significantly higher serum dsDNA levels compared to those in the South (1.00 vs. 0.96 ng/ml), and those in medium latitude regions had higher levels than their counterparts in areas with extreme latitudes (0.98 vs. 0.96 ng/ml). Furthermore, individuals in regions with low to medium ultraviolet exposure demonstrated higher serum dsDNA concentrations than those in areas with high ultraviolet levels (1.03 vs. 0.93 ng/ml), and individuals in winter showed higher levels than those in summer (1.03 vs. 0.92 ng/ml). Factors such as sex, UV index, humidity, and sunshine duration were inversely related to serum dsDNA levels, while age and daylight hours showed a positive association. These findings suggest that meteorological and climatic factors play a role in influencing serum dsDNA levels.

Tauroursodeoxycholic acid targets HSP90 to promote protein homeostasis and extends healthy lifespan.

As the elderly population expands, the pursuit of therapeutics to reduce morbidity and extend lifespan has become increasingly crucial. As an FDA-approved drug for chronic cholestatic liver diseases, tauroursodeoxycholic acid (TUDCA), a natural bile acid, offers additional health benefits beyond liver protection. Here, we show that TUDCA extends the lifespan and healthspan of C. elegans. Importantly, oral supplementation of TUDCA improves fitness in old mice, including clinically relevant phenotypes, exercise capacity and cognitive function. Consistently, TUDCA treatment drives broad transcriptional changes correlated with anti-aging characteristics. Mechanistically, we discover that TUDCA targets the chaperone HSP90 to promote its protein refolding activity. This collaboration further alleviates aging-induced endoplasmic reticulum (ER) stress and facilitates protein homeostasis, thus offering resistance to aging. In summary, our findings uncover new molecular links between an endogenous metabolite and protein homeostasis, and propose a novel anti-aging strategy that could improve both lifespan and healthspan.

Case report: Two cases of prostate adenocarcinoma progressing to rare sarcomatoid carcinoma with normal PSA levels following endocrine therapy.

Background: Patients with prostate adenocarcinoma undergoing regular endocrine therapy may maintain normal PSA levels during follow-up, yet still progress to the highly malignant and rare prostatic sarcomatoid carcinoma, which is seldom reported. This article presents two case studies of prostatic sarcomatoid carcinoma. To date, only a few publications have described prostatic sarcomatoid carcinoma, and the clinical, morphological, and molecular dimensions of prostate adenocarcinoma warrant further investigation. Case description: Patient A was admitted two years ago due to difficulty urinating, with a PSA level of 6.35 ng/ml. A prostate needle biopsy was performed, and the postoperative pathology diagnosed prostate adenocarcinoma with a Gleason score of 9 (5 + 4, grade group 5). Citing personal reasons, the patient declined a radical prostatectomy and instead received ongoing androgen deprivation therapy (ADT), comprising goserelin, abiraterone, and prednisone. During follow-up, regular PSA tests showed no abnormalities. One year ago, the patient was admitted again due to difficulty urinating and hematuria, choosing to address only the urethral obstruction. Transurethral resection of the prostate was performed, and the postoperative pathology diagnosed sarcomatoid carcinoma of the prostate. Patient B was admitted three years ago due to difficulty urinating accompanied by hematuria. A prostate MRI and a whole-body radionuclide bone scan suggested prostate cancer with bone metastasis. Prostate needle biopsy confirmed the diagnosis. The patient was then regularly treated with androgen deprivation therapy, using goserelin. Throughout the follow-up period, the PSA levels consistently remained within normal limits. One year ago, the patient was admitted due to rectal bleeding. It was speculated that the symptoms of rectal bleeding might have been caused by the prostate cancer invading the rectal wall. A prostate needle biopsy was performed, and the pathology diagnosed sarcomatoid carcinoma of the prostate. Conclusions: This case underscores the inadequacy of relying solely on PSA levels to monitor high-grade prostate adenocarcinoma during endocrine therapy, as patients may progress to highly malignant atypical variants despite normal PSA levels. We propose that for high-grade prostate cancer patients who are unable to undergo radical prostatectomy, regular and frequent MRI screenings or repeat biopsies should be integral during endocrine therapy and follow-up. Furthermore, a detailed review of the patient's treatment history and clinical data, including immunohistochemical findings, might offer deeper clinical insights into prostatic sarcomatoid carcinoma.

An innovative functional compatibility strategy for poly (lactic acid) and polypropylene carbonate blends to achieve superior toughness, degradability, and optical properties.

This study, for the first time, unveils the potential of dibutyl itaconate (DBI) in enhancing the compatibility between PLA (poly (lactic acid)) and PPC (polypropylene carbonate), systematically investigating the effects of DBI amount on the thermal, optical, rheological, mechanical, and degradation properties and microstructure of the PLA/PPC/DBI blends. The results showed that DBI could chemically react with PLA and PPC, forming a PLA-co-DBI-co-PPC copolymer structure, thereby improving the compatibility between PLA and PPC. When the DBI amount reached 8 wt%, only one Tg was observed in the blend system, and no distinct phase interface was visible in the fracture surface of the blend specimens. This indicated that at this DBI amount, the PLA and PPC had transitioned from a partially compatible system to a fully compatible system. With the increase in DBI amount in the system, the elongation at break and notched impact strength of the blends initially increased and then decreased, while the storage modulus, loss modulus, and complex viscosity showed a gradual downward trend. When the DBI amount increased to 10 wt%, the flexibility of the blends reached its peak, with the values rising to 494.7 % and 8494.1 J/m2, respectively, representing 13.7 times and 2.5 times those of the neat PLA/PPC blends. At this point, the impact specimens exhibited significant plastic flow in the direction of force, showing distinct ductile fracture characteristics. Meanwhile, the degradation performance of the PLA/PPC blends increased with the addition of DBI. The introduction of DBI effectively facilitated the penetration of water molecules into the PLA/PPC molecular chains, enhancing the hydrolysis of ester bonds, leading to a maximum mass loss rate of 84.1 %, which was significantly higher than the 20.3 % of the neat PLA/PPC blends. In addition, the addition of DBI significantly reduced the haze of the blends while maintaining high light transmittance, demonstrating excellent optical properties (light transmittance remained above 92.4 %, and haze decreased from 37.1 % to 11.1 %). In conclusion, this study provides a new approach for the development of high-performance PLA-based biodegradable composites. The resulting blends exhibit excellent toughness, degradation performance, and optical properties, significantly enhancing their application potential in fields such as disposable products, packaging, agriculture, and 3D printing materials.

Sacubitril/valsartan alleviates myocardial infarction-induced inflammation in mice by promoting M2 macrophage polarisation via regulation of PI3K/Akt pathway.

BACKGROUND: Macrophage polarisation-mediated inflammation plays a critical role in ventricular remodelling after myocardial infarction (MI). Sacubitril/Valsartan (Sac/Val) is an angiotensin receptor-neprilysin inhibitor that has shown beneficial effects on MI and heart failure. This study aims to further explore the mechanisms by which Sac/Val exerts its protective effects against MI. METHODS: A mouse MI model was induced by ligating the left anterior descending coronary artery, followed by Sac/Val administration. TTC staining and Masson trichrome staining were employed for estimating myocardial infarct size and fibrosis, respectively. The expression levels of proinflammatory factors were determined by ELISA and RT-qPCR. Flow cytometry and immunofluorescence staining were implemented to detect CD206-positive cell infiltration in mouse hearts. Western blotting was conducted to assess protein levels of Arg1, pro-fibrotic factors, and PI3K/Akt signalling-related markers. RESULTS: Sac/Val treatment reduced myocardial infarct size and fibrosis in mice after MI. Sac/Val administration decreased proinflammatory cytokine production and facilitated M2 macrophage polarisation in MI mouse cardiac tissues. Sac/Val activated PI3K/Akt signalling in MI mouse hearts. Blocking PI3K/Akt signalling counteracted Sac/Val-mediated protective effects in MI mice. CONCLUSION: Sac/Val ameliorates MI-induced inflammation by facilitating M2 macrophage polarisation and activating PI3K/Akt signalling.

Construction of thyroid cancer classification and iodine metabolism related diagnostic model using thyroid differentiation score and bioinformation.

To more accurately diagnose and treat patients with different subtypes of thyroid cancer, we constructed a diagnostic model related to the iodine metabolism of THCA subtypes. THCA expression profiles, corresponding clinicopathological information, and single-cell RNA-seq were downloaded from TCGA and GEO databases. Genes related to thyroid differentiation score were obtained by GSVA. Through logistic analyses, the diagnostic model was finally constructed. DCA curve, ROC curve, machine learning, and K-M analysis were used to verify the accuracy of the model. qRT-PCR was used to verify the expression of hub genes in vitro. There were 104 crossover genes between different TDS and THCA subtypes. Finally, 5 genes (ABAT, CHEK1, GPX3, NME5, and PRKCQ) that could independently predict the TDS subpopulation were obtained, and a diagnostic model was constructed. ROC, DCA, and RCS curves exhibited that the model has accurate prediction ability. K-M and subgroup analysis results showed that low model scores were strongly associated with poor PFI in THCA patients. The model score was significantly negatively correlated with T cell follicular helper. In addition, the diagnostic model was significantly negatively correlated with immune scores. Finally, the results of qRT-PCR corresponded with bioinformatics results. This diagnostic model has good diagnostic and prognostic value for THCA patients, and can be used as an independent prognostic indicator for THCA patients.

Research progress on the regulatory mechanism of cell senescence in arsenic toxicity: a systematic review.

As an element with metalloid properties, arsenic is pervasively present in the environment and is recognized as a potent carcinogen. Consequently, the issue of human arsenic exposure has become a significant concern within the global public health sector. Numerous studies have indicated that arsenic induces cellular senescence through various mechanisms, including triggering epigenetic alterations, inducing the senescence-associated secretory phenotype (SASP), promoting telomere shortening, and causing mitochondrial dysfunction. This article collates and summarizes the latest research advancements on the involvement of cellular senescence in arsenic toxicity and explores the mechanisms of arsenic-induced toxicity. This study aims to provide new perspectives and directions for future research on arsenic toxicity and the development of prevention and treatment strategies.

Cardiovascular comorbidities among patients with psoriasis: a national register-based study in China.

This study aims to illustrate epidemiology of comorbid CVD in the real-world clinical setting of patients with psoriasis in China. We used data of adult patients with psoriasis who were registered in the register of China National Clinical Center for Skin and Immune Diseases between August 2020 and September 2021. Psoriasis was clinically diagnosed following the national guidelines. Univariate and multivariate logistic regression models were used to examine the factors associated with comorbid CVD in patients with psoriasis. Of the 11,560 psoriasis patients (age ≥ 18 years, mean age 41.87 years, 64.88% males), 236 were ascertained with CVD, with the overall prevalence being 2.62%. Multivariate logistic regression analysis suggested that the odds ratio (95% confidence interval) of CVD in psoriasis patients was 2.27 (2.03-2.54) for older age (per 10-year increment), 0.65 (0.48-0.90) for female, 2.07 (1.39-3.06) for obesity (BMI ≥ 28 vs. < 24 kg/m2), 2.55 (1.85-2.52) for smoking, 7.63 (5.86-9.94) for hypertension, 4.27 (3.76-4.85) for diabetes, 1.14 (1.00-1.30) for having a history of drug allergy, 2.27 (1.61-3.20) for having family history of psoriasis, and 1.76 (1.16-2.67) for severe disease (severe vs. mild) with a dose-response relationship (Ptrend < 0.001). In patients with psoriasis, comorbid CVD was associated with smoking, obesity, hypertension, diabetes, history of drug allergy, family history of psoriasis, and the psoriasis severity.

Rapid and accurate quantification of trypsin activity using integrated infrared and ultraviolet spectroscopy with data fusion techniques.

Proteases play a crucial role in industrial enzyme formulations, with activity fluctuations significantly impacting product quality and yield. Therefore, developing a method for precise and rapid detection of protease activity is paramount. This study aimed to develop a rapid and accurate method for quantifying trypsin activity using integrated infrared (IR) and ultraviolet (UV) spectroscopy combined with data fusion techniques. The developed method evaluates the enzymatic activity of trypsin under varying conditions, including temperature, pH, and ionic strength. By comparing different data fusion methods, the study identifies the optimal model for accurate enzyme activity prediction. The results demonstrated significant improvements in predictive performance using the feature-level data fusion approach. Additionally, substituting the spectral data of the samples in the validation sets into the best prediction model resulted in a minimal residual difference between predicted and true values, further verifying the model's accuracy and reliability. This innovative approach offers a practical solution for the efficient and precise quantification of enzyme activity, with broad applications in industrial processes.

A comprehensive study on solvent effect and establishment of n-hexane solvent system based normal-phase liquid chromatography × reversed-phase liquid chromatography for isolation of natural products.

Reversed-phase liquid chromatography (RPLC) represents an effective separation method, and is widely employed as the second dimension in most 2D-LC systems. Nevertheless, the solvent effect of the eluent from the first dimension on RPLC presents a challenge to the online coupling of RPLC with other separation modes, particularly normal phase liquid chromatography (NPLC). To address this issue, a comprehensive understanding of the solvent effect is essential. Following a comprehensive investigation into the influence of diverse solvents on RPLC separations, it was observed that alkane solvents, such as n-hexane, exhibited a pronounced tendency to be retained during RPLC separations. Such solvents do not affect the analysis of samples with weaker retention abilities than themselves, even when a large injection volume is used. The solvent effect was thus reduced by employing n-hexane-based solvent dilution. Leveraging the markedly enhanced solvent tolerance and extensive injection volume in RPLC, a versatile integration of the NPLC and RPLC was devised, necessitating merely a purge pump and a 10 port 2 position valve in conjunction with two sample loops. The novel 2D-LC system was then deployed for the analysis of propolis, a naturally occurring complex sample, and demonstrated remarkable separation efficiency.

Does digital inclusive finance promote carbon emission reduction of enterprises.

Can the information technology revolution lead to carbon emission reduction for firms? This study extends the limited evidence in the literature and investigate the role and mechanism of digital inclusive finance on enterprises' carbon emissions using panel data of 247 prefectural-level cities and 6019 industrial enterprises in China. Our findings indicate that digital inclusive finance can promote enterprise carbon emission reduction, and this effect remains significant after the instrumental variable estimation test. The effect has regional heterogeneity and the development of digital inclusive finance in the area east of Hu Huanyong line has a significant impact on reducing enterprise carbon emission. The role of digital inclusive finance is heterogeneous in enterprise ownership, with a remarkable effect in non-state-owned enterprises. Sub-dimension analysis indicates that the breadth of coverage, depth of use, and degree of digitalization of digital inclusive finance have differential effects on reducing enterprise carbon emissions. The stepwise regression method shows that the impact of digital inclusive finance on enterprise carbon emissions can be passed through effect of technological progress, environmental protection investment and financing constrain. This study has significant reference value for evaluating the impact of financial inclusion and policy implications in formulating differentiated strategies for achieving carbon emission reduction efficiency in enterprises.

Research progress of ferroptosis regulating lipid peroxidation and metabolism in occurrence and development of primary liver cancer.

As a highly aggressive tumor, the pathophysiological mechanism of primary liver cancer has attracted much attention. In recent years, factors such as ferroptosis regulation, lipid peroxidation and metabolic abnormalities have emerged in the study of liver cancer, providing a new perspective for understanding the development of liver cancer. Ferroptosis regulation, lipid peroxidation and metabolic abnormalities play important roles in the occurrence and development of liver cancer. The regulation of ferroptosis is involved in apoptosis and necrosis, affecting cell survival and death. Lipid peroxidation promotes oxidative damage and promotes the invasion of liver cancer cells. Metabolic abnormalities, especially the disorders of glucose and lipid metabolism, directly affect the proliferation and growth of liver cancer cells. Studies of ferroptosis regulation and lipid peroxidation may help to discover new therapeutic targets and improve therapeutic outcomes. The understanding of metabolic abnormalities can provide new ideas for the prevention of liver cancer, and reduce the risk of disease by adjusting the metabolic process. This review focuses on the key roles of ferroptosis regulation, lipid peroxidation and metabolic abnormalities in this process.

Ferroptosis regulating lipid peroxidation metabolism in the occurrence and development of gastric cancer.

BACKGROUND: Gastric cancer is one of the most common malignant tumors in the world, and its occurrence and development involve complex biological processes. Iron death, as a new cell death mode, has attracted wide attention in recent years. However, the regulatory mechanism of iron death in gastric cancer and its effect on lipid peroxidation metabolism remain unclear. AIM: To explore the role of iron death in the development of gastric cancer, reveal its relationship with lipid peroxidation, and provide a new theoretical basis for revealing the molecular mechanism of the occurrence and development of gastric cancer. METHODS: The process of iron death in gastric cancer cells was simulated by cell culture model, and the occurrence of iron death was detected by fluorescence microscopy and flow cytometry. The changes of gene expression related to iron death and lipid peroxidation metabolism were analyzed by high-throughput sequencing technology. In addition, a mouse model of gastric cancer was established, and the role of iron death in vivo was studied by histology and immunohistochemistry, and the level of lipid peroxidation was detected. These methods comprehensively and deeply reveal the regulatory mechanism of iron death on lipid peroxidation metabolism in the occurrence and development of gastric cancer. RESULTS: Iron death was significantly activated in gastric cancer cells, and at the same time, associated lipid peroxidation levels increased significantly. Through high-throughput sequencing analysis, it was found that iron death regulated the expression of several genes related to lipid metabolism. In vivo experiments demonstrated that increased iron death in gastric cancer mice was accompanied by a significant increase in lipid peroxidation. CONCLUSION: This study confirmed the important role of iron death in regulating lipid peroxidation metabolism in the occurrence and development of gastric cancer. The activation of iron death significantly increased lipid peroxidation levels, revealing its regulatory mechanism inside the cell.

Advances in targeted therapy for human epidermal growth factor receptor 2 positive in advanced gastric cancer.

Emerging therapeutic methods represented by targeted therapy are effective supplements to traditional first-line chemoradiotherapy resistance. Human epidermal growth factor receptor 2 (HER2) is one of the most important targets in targeted therapy for gastric cancer. Trastuzumab combined with chemotherapy has been used as the first-line treatment for advanced gastric cancer. The safety and efficacy of pertuzumab and margetuximab in the treatment of gastric cancer have been verified. However, monoclonal antibodies, due to their large molecular weight, inability to penetrate the blood-brain barrier, and drug resistance, lead to decreased therapeutic efficacy, so it is necessary to explore the efficacy of other HER2-targeting therapies in gastric cancer. Small-molecule tyrosine kinase inhibitors, such as lapatinib and pyrrotinib, have the advantages of small molecular weight, penetrating the blood-brain barrier and high oral bioavailability, and are expected to become the drugs of choice for perioperative treatment and neoadjuvant therapy of gastric cancer after validation by large-scale clinical trials in the future. Antibo-drug conjugate, such as T-DM1 and T-DXd, can overcome the resistance of monoclonal antibodies despite their different mechanisms of tumor killing, and are a supplement for the treatment of patients who have failed the treatment of monoclonal antibodies such as trastuzumab. Therefore, after more detailed stratification of gastric cancer patients, various gastric cancer drugs targeting HER2 are expected to play a more significant role.

[Corrigendum] P2Y2 receptor promotes the migration and invasion of breast cancer cells via EMT­related genes Snail and E­cadherin.

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that there appeared to be two instances of overlapping data panels comparing between the cell migration and invasion assay data shown in Figs. 4 and 6 on p. 143 and 145, respectively, such that data which were intended to represent the results from differently performed experiments had apparently been derived from the same original sources. In addition, the authors themselves realized that incorrect western blotting data for Snail protein in Fig. 10A on p. 147 had been included in the figure.  The authors were able to re­examine their original data files, and realized that the affected data panels in these figures had inadvertently been incorporated into them incorrectly. The revised versions of Figs. 4, 6, and 10, featuring the correct data for the 'NC / Control' panels in Fig. 4B and C and the 'siRNA2 / ATP 12 h' panels in Fig. 4A and B, a replacement data panel for the 'siRNA1 / Control' experiment in Fig. 6, and the correct western blotting data for Snail protein in Fig. 10A (together with a revised histogram for the MCF7 cell line relating to Fig. 10A) are shown on the next three pages. The authors wish to emphasize that the errors made in compiling these figures did not affect the overall conclusions reported in the paper, and they are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this corrigendum. All the authors agree to the publication of this corrigendum, and also apologize to the readership for any inconvenience caused. [Oncology Reports 39: 138­150, 2018; DOI: 10.3892/or.2017.6081].

Regulation and mechanism of enzyme metabolism in germinated hemp seeds by ultrasound combined with exogenous calcium chloride treatment.

γ-aminobutyric acid (GABA) plays an important role in anti-anxiety by inhibiting neurotransmitter in the central nervous system (CNS) of mammals, which is generated in the germinating seeds. The key enzymes activity of GABA metabolism pathway and nutrients content in hemp seeds during germination were studied after treated with ultrasound and CaCl2. The mechanism of exogenous stress on key enzymes in GABA metabolism pathway was investigated by molecular dynamics simulation. The results showed that ultrasonic combined with 1.5 mmol·L-1CaCl2 significantly increased the activities of glutamate decarboxylase (GAD) and GABA transaminase (GABA-T) in seeds, and promoted the conversion of glutamate to GABA, resulting in the decrease of glutamate content and the accumulation of GABA. Molecular dynamics simulations revealed that Ca2+ environment enhanced the activity of GAD and GABA-T enzymes by altering their secondary structure, exposing their hydrophobic residues. Ultrasound, germination and CaCl2 stress improved the nutritional value of hemp seeds.

A highly malignant succinate dehydrogenase A­deficient renal cell carcinoma with bone metastasis misdiagnosed as hereditary leiomyomatosis and renal cell carcinoma: A case report.

Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) is an autosomal dominant syndrome caused by heterozygous pathogenic germline variants of the SDH gene. SDH mutations are associated with an increased risk of developing RCC, although studies describing SDH-deficient RCC are currently limited. The present study reported a case of SDH-deficient RCC with high malignancy and rare bone metastasis. The patient was diagnosed with a right renal mass through B-mode ultrasound imaging and showed a carcinoma embolus in the right renal vein and inferior vena cava through kidney contrast-enhanced computed tomography. A whole-body bone scan showed radionuclide accumulation in the upper end of the left humerus, which indicated possible pathological bone destruction. As a result, surgical resection was performed. The postoperative pathology indicated a high-grade RCC and although the specific classification remained uncertain, hereditary leiomyomatosis and RCC was suspected. Subsequently, a germline mutation of the succinate dehydrogenase complex flavoprotein subunit A gene was identified through high-throughput sequencing (c.1A>G, p. Met1?) and immunohistochemistry demonstrated the loss of succinate dehydrogenase complex flavoprotein subunit B expression. Postoperatively, the patient underwent radiotherapy and targeted therapy. After 6 months of follow-up treatment, there was no indication of recurrence or metastasis on thoracoabdominal CT and whole-body bone scintigraphy. Based on the present report, germline screening should potentially be encouraged in early-onset patients as family history or pathological results may not provide sufficient information for the early, differential diagnosis of SDH-deficient RCC.

Retrospective studies and quantitative proteomics reveal that abnormal expression of blood pressure, blood lipids, and coagulation related proteins is associated with hypospadias.

Hypospadias refers to the abnormal position of the male urethral orifice, which not only leads to urination disorder but also causes sexual dysfunction in adulthood. However, the complex and diverse pathogenic factors of hypospadias are still unclear. To study the pathogenesis and prognosis of hypospadias, we counted the serological indexes of children with hypospadias, and found that sSBP, TC and LDL increased in children with mild, moderate and severe hypospadias. Subsequently, we used quantitative proteomics to find differential proteins in mild, moderate and severe hypospadias. After bioinformatics analysis and biochemical experiments on the screened DEPs, we found that the expression of proteins related to immune inflammation, coagulation, blood pressure and inflammation, and blood lipid were differential expressed in the prepuce tissue of children with hypospadias. We further confirmed that the proteins FGB, FGG, SERPINA1, and AGT involved in the angiotensin system, cholesterol metabolism, and coagulation were significantly up-regulated by biochemical experiments. In particular, the AGT protein of the angiotensin system involved in blood pressure regulation, we have shown that it increases with the severity of hypospadias. This study suggests that children with hypospadias are more likely to suffer from hyperlipidemia and cardiovascular disease (CVD). Our findings provide a theoretical basis for early monitoring of blood lipids and blood pressure to prevent CVD in children with hypospadias.

[Efficacy of Decitabine Combined with Preexcitation Regimen in Treatment of Newly Diagnosed AML Patients Who Did not Respond to Initial Standard Induction Chemotherapy].

OBJECTIVE: To investigate the efficacy of decitabine combined with preexcitation regimen in the treatment of newly diagnosed acute myeloid leukemia (AML) patients who have not been relieved by the first standard induction chemotherapy and its influence on the relative content of regulatory T lymphocytes (Tregs). METHODS: The clinical data of 102 newly diagnosed AML patients (except acute promyelocytic leukemia) who did not relieve after initial standard induction chemotherapy in Shaanxi Provincial People's Hospital from March 2013 to March 2019 were retrospectively analyzed. Fifty-one patients who accepted pre-excitation regimen were divided into regular group, while another 51 patients treated with decitabine combined with pre-excitation regimen were divided into combination group. The efficacy, incidence of toxic and side effects, Core Scale of Quality of Life (QLQ-C30) score before and after treatment, T lymphocyte subsets (CD3+, CD4+, CD4+/CD8+, Tregs) and 3-year overall survival (OS) rate were compared between the two groups. RESULTS: The total effective rate of combination group was 80.39%, which was significantly higher than 62.75% of regular group (P < 0.05). After treatment, the QLQ-C30 score of combination group was 60.27±6.96, which was significantly lower than 65.73±7.96 of regular group (P < 0.001). There was no statistical difference in the incidence of toxic and side effects between the two groups (P >0.05). After treatment, the levels of CD3+, CD4+, CD4+/CD8+ in the combination group were higher than those in the regular group (all P < 0.001), while Treg was lower (P < 0.001). The 3-year OS rate in the combination group was 72.55%, which was significantly higher than 52.94% in the regular group (P < 0.001). CONCLUSION: Decitabine combined with preexcitation regimen has a significant effect on AML patients who have not been alleviated by standard induction chemotherapy in the first course of treatment. It can reduce anti-tumor immune suppression and improve immune function by regulating the relative content of Tregs, thus prolongs survival time and improves life quality of patients without increasing adverse reactions.

Personalized embryo transfer guided by rsERT improves pregnancy outcomes in patients with repeated implantation failure.

Introduction: Embryo implantation requires synchronous communication between the embryo and maternal endometrium. Inadequate maternal endometrial receptivity is one of the principal causes for embryo implantation failure [especially repeated implantation failure (RIF)] when biopsied good-quality euploid embryos are transferred. An RNA-seq-based endometrial receptivity test (rsERT) was previously established to precisely guide successful embryo implantation. In this study, we aimed to evaluate the effect of personalized embryo transfer (pET) via rsERT on the clinical outcomes in patients with RIF. Methods: A total of 155 patients with RIF were included in the present retrospective study and were divided into two groups: 60 patients who underwent rsERT and pET (Group rsERT) and 95 patients who underwent standard frozen embryo transfer (FET) without rsERT (Group FET). Reproductive outcomes were compared for patients who underwent rsERT-guided pET and standard FET. Results: Forty percent (24/60) of the patients who underwent rsERT were receptive, and the remaining 60% (36/60) were non-receptive. The positive human chorionic gonadotropin (ß-hCG) rate (56.3% vs. 30.5%, P = 0.003) and clinical pregnancy rate (43.8% vs. 24.2%, P = 0.017) were significantly higher in Group rsERT patients than in FET group patients. Additionally, Group rsERT patients also showed a higher implantation rate (32.1% vs. 22.1%, P = 0.104) and live birth rate (35.4% vs. 21.1%, P = 0.064) when compared with FET patients, although without significance. For subpopulation analysis, the positive ß-hCG rate, clinical pregnancy rate, implantation rate, and live birth rate of receptive patients were not statistically significant different from those of non-receptive patients. Conclusions: The rsERT can significantly improve the pregnancy outcomes of RIF patients, indicating the clinical potential of rsERT-guided pET.