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AIM: To evaluate the characteristics of choriocapillary blood flow in different patients with diabetic retinopathy(DR)based on the measurement of choriocapillaris(CC)perfusion density(PFD)using ultra-high-speed swept-source optical coherence tomography angiography(SS-OCTA)METHODS: The cross-sectional observational study was conducted on 139 cases(139 eyes)who admitted to the Second People's Hospital of Hefei, including 115 DR cases(115 eyes)and 24 control cases(24 eyes). The color retinal images were graded according to the Early Treatment Diabetic Retinopathy Study(ETDRS)scale, and the DR eyes were classified into non-DR group, nonproliferative diabetic retinopathy(NPDR)group, NPDR combined with diabetic macular edema(DME)group and proliferative diabetic retinopathy(PDR)group. The ultra-high-speed SS-OCTA was used to scan a 3mm×3mm region centered on the macular central fovea, the CC perfusion area was measured by the built-in software, and PFD was calculated. Multivariable linear regressions were used to evaluate the correlation between PFD of CC and DR degree.RESULTS: The degree of DR had a correlation with blood perfusion of CC after adjusting for various confounding factors. When compared to the control group, the PFD of CC in the central fovea of the NPDR group decreased by 9.358 units(95%CI -18.484~-0.232, P=0.045)and 9.284 units in the paracentral fovea(95%CI -18.487~-0.090, P=0.048); In the NPDR combined with DME group, the central fovea CC PFD decreased by 18.173 units(95%CI -28.583~-7.762, P=0.001), while the paracentral fovea decreased by 17.032 units(95%CI -27.521~-6.544, P=0.002); In the PDR group, the central fovea CC PFD decreased by 28.309 units(95%CI -39.978~-16.640, P<0.001), while the paracentral fovea decreased by 25.841 units(95%CI -37.597~-14.085, P<0.001).CONCLUSION: The macular perfusion can be objectively quantified by the measurement of CC PFD with ultra-high-speed SS-OCTA. The CC PFD in the macular region was significantly reduced in more advanced stages of DR. Furthermore, future research should focus on longitudinal studies in the causal relationship between CC perfusion and DR progression.
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When it comes to diabetic patients, persistent hyperglycemia and associated pathological conditions will not only cause diabetic retinopathy(DR)but also have an impact on the metabolism of vitreous, leading to diabetic vitreopathy. Owing to the adjacent anatomical position between the vitreous and retina, diabetic vitreopathy and DR are mutually promoted. Changes in vitreoretinal interface such as posterior vitreous detachment(PVD)and vitreoschisis, provide a scaffold for fibrovascular proliferative membrane and are closely associated with pars plana vitrectomy(PPV). This article sorts out the variation of diabetic patients' vitreous structure and biochemical components, along with the changes in the vitreous-retinal interface, particularly for the related research on its relationship with proliferative diabetic retinopathy(PDR), aiming at providing further cognition of diabetic vitreopathy as well as references for DR treatment and formulation of PPV.
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Objective To investigate the efficacy of continuous hepatic arterial infusion chemotherapy (HAIC) with the FOLFOX regimen and its multimodality therapeutic regimen in the treatment of patients with advanced hepatocellular carcinoma, as well as the influencing factors for prognosis. Methods A retrospective analysis was performed for the clinical data of 66 patients with advanced hepatocellular carcinoma who received continuous HAIC with FOLFOX regimen in Nanfang Hospital, Southern Medical University, from September 2018 to November 2021. The patients were observed in terms of objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), and median overall survival (mOS) after treatment, and treatment-related adverse reactions were recorded. For the patients with portal vein tumor thrombus, the effect of the treatment on portal vein tumor thrombus was assessed. The Kaplan-Meier method was used for survival analysis, and the Cox regression analysis was used to investigate the influencing factors for prognosis. Results According to the RECIST1.1 criteria, FOLFOX-HAIC and its multimodality therapeutic regimen achieved an ORR of 33.3% (22/66) and a DCR of 86.4% (57/66) in the treatment of 66 patients with advanced hepatocellular carcinoma, with an mPFS time of 8.2 months and an mOS time of 22.1 months. Among the 39 patients with portal vein tumor thrombus, 2 achieved complete remission, 8 achieved partial remission, 24 achieved stable disease, and 5 had disease progression, with an ORR of 25.6% (10/39) and a DCR of 87.2% (34/39). The main adverse reactions included gastrointestinal reactions (16.7%, 11/66), pyrexia (12.1%, 8/66), liver area pain (10.6%, 7/66), bone marrow suppression (3.0%, 2/66), and contrast agent allergy (3.0%, 2/66), and there were no grade > Ⅳ toxic or side effects or deaths caused by such complications. The Cox regression analysis showed that extrahepatic metastasis (hazard ratio [ HR ]=2.668, 95% confidence interval [ CI ]: 1.357-5.245, P < 0.05) and prothrombin time (PT) ( HR =1.282, 95% CI : 1.080-1.630, P < 0.05) were independent risk factors for PFS, and aspartate aminotransferase level ( HR =1.008, 95% CI : 1.002-1.013, P < 0.05) and PT ( HR =1.303, 95% CI : 1.046-1.630, P < 0.05) were independent risk factors for OS. Conclusion FOLFOX-HAIC and its multimodality therapeutic regimen has a certain clinical effect with controllable adverse reactions in the treatment of advanced hepatocellular carcinoma.
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Breast cancer has become the most prevalent malignant tumor among women, putting the health of women at serious risk. Screening for lead compounds in the active ingredients of plant that are effective and less toxic continues to be an important strategy for treating breast cancer. Gerbeloid J, a coumarin isolated from Gerbera piloselloides (L.) Cass., showed significant anti-cancer activity. But there is no report on the effect and mechanism of gerbeloid J on cycle and apoptosis of breast cancer. By using the CCK-8, clone formation, and PI staining assays, the effects of gerbeloid J on the proliferation of MCF-7 and MDA-MB-231 cells were assessed in this study. The effects of gerbeloid J on the apoptosis and mitochondrial function of MCF-7 and MDA-MB-231 cells were assessed using DAPI, Annexin V/TO-PRO-3, Rhod-2 AM, TMRM, DCFDA staining assays, and Western blot. The results demonstrated that gerbeloid J regulated the P21/CDC25C/CDK-1/cyclin B1 pathway and arrested the cell cycle at G2/M phase to suppressed the proliferation of MCF-7 and MDA-MB-231 cells. Additionally, gerbeloid J induced apoptosis through the stimulation of mitochondrial calcium excess, reduction of mitochondrial membrane potential, and promotion of ROS generation, and its mechanism was related to the activation of mitochondrial apoptotic pathway. In conclusion, by regulating the P21/CDC25C/CDK-1/cyclin B1 pathway and activating the mitochondrial apoptosis pathway, gerbeloid J could cause breast cancer cell cycle arrest and apoptosis, which might offer a promising candidate for the creation of new drugs against breast cancer.
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AIM: To optimize the technique of intravenous injection of Evans blue and retinal preparations in mice, improving the accuracy and repeatability of staining experiment of retinal preparations.METHODS: C57BL/6 male mice were intravenous injected with 10g/L(1%)Evans Blue 0.3mL and circulated in vivo for 10 or 20min, and the eyes were removed after sacrificed and fixed in 4% paraformaldehyde for 20, 40 or 60min. When failure of intravenous injection, the experiment was remediated by intraperitoneal injection of 1% Evans Blue 0.3mL, circulated in vivo for 3h and fixed for 60min to observe morphology, distribution and leakage of the retinal vessels. Besides, we compared the morphology, distribution and leakage of the retinal vessels after intravenous injection with those after intraperitoneal injection to determine the optimal conditions for in vivo circulation time and retinal preparations.RESULTS: After intravenous injection, compared to the retinal vascular condition under 20min in vivo circulation time of Evans blue and 20 or 40min of fixation, with 10min of in vivo Evans blue circulation and 60min of fixation, the morphology of retinal vascular was more intact with less retinal vascular leakage, and the vascular branches are clear. When intravenous injection failed, remediated results from intraperitoneal injection showed that the morphology and distribution of retinal vessels were intact. There was no significant difference in morphology, distribution and leakage of the retinal vessels after 3h of intraperitoneal Evans blue circulation compared to 10min intravenous Evans blue circulation.CONCLUSION: This experiment optimizes the protocol, improves the accuracy and reproducibility of retinal preparations, and provides a reference for the study of related retinal vascular diseases.
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AIM: To investigate the changes in retinal and choroidal blood flow after pars plana vitrectomy(PPV)for proliferative diabetic retinopathy(PDR).METHODS: A cross-sectional study was conducted on 35 patients(35 eyes)who were diagnosed as monocular PDR and received 23GPPV in ophthalmology department of the Second People's Hospital of Hefei between September 2020 and July 2022. All eyes underwent swept-source optical coherence tomography angiography(SS-OCTA)examination. Retinal and choroidal vascular parameters within 3mm×3mm of macular zone were measured by built-in analyzer, and its correlation with postoperative best corrected visual acuity(BCVA)was analyzed.RESULTS: The follow-up was 1~22(average 9.72±6.67)mo. At the last follow-up, flow area(FA)of intermediate capillary plexus(ICP)layer in paranasal foveal region was significantly reduced in PPV eyes(0.31±0.06mm2)compared with contralateral eyes(0.38±0.05mm2), and FA of deep capillary plexus(DCP)in temporal foveal region was significantly lower in PPV eyes(0.19±0.08mm2)than contralateral eyes(0.27±0.07mm2; all P<0.05). Choroidal vascularity index(CVI)were lower in PPV eyes than contralateral eyes in parafoveal subregions except temporal region(P<0.05). After PPV, BCVA had a certain correlation with the density and FA of middle and deep retinal vessels.CONCLUSIONS: Eyes with severe PDR may be prone to having a decrease in the DCP and parafoveal choroidal perfusion in the parafoveal regions after PPV than contralateral eyes.
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OBJECTIVE@#Huangqi Decoction (HQD), a classical traditional Chinese medicine formula, has been used as a valid treatment for alleviating liver fibrosis; however, the underlying molecular mechanism is still unknown. Although our previous studies showed that microRNA-663a (miR-663a) suppresses the proliferation and activation of hepatic stellate cells (HSCs) and the transforming growth factor-β/small mothers against decapentaplegic (TGF-β/Smad) pathway, whether long noncoding RNAs (lncRNAs) are involved in HSC activation via the miR-663a/TGF-β/Smad signaling pathway has not yet reported. The present study aimed to investigate the roles of lncRNA lnc-C18orf26-1 in the activation of HSCs and the mechanism by which HQD inhibits hepatic fibrosis.@*METHODS@#The expression levels of lnc-C18orf26-1, miR-663a and related genes were measured by quantitative reverse transcription-polymerase chain reaction. HSCs were transfected with the miR-663a mimic or inhibitor and lnc-C18orf26-1 small interfering RNAs. The water-soluble tetrazolium salt-1 assay was used to assess the proliferation rate of HSCs. Changes in lncRNA expression were evaluated in miR-663a-overexpressing HSCs by using microarray to identify miR-663a-regulated lncRNAs. RNA hybrid was used to predict the potential miR-663a binding sites on lncRNAs. Luciferase reporter assays further confirmed the interaction between miR-663a and the lncRNA. The expression levels of collagen α-2(I) chain (COL1A2), α-smooth muscle actin (α-SMA) and TGF-β/Smad signaling pathway-related proteins were determined using Western blotting.@*RESULTS@#Lnc-C18orf26-1 was upregulated in TGF-β1-activated HSCs and competitively bound to miR-663a. Knockdown of lnc-C18orf26-1 inhibited HSC proliferation and activation, downregulated TGF-β1-stimulated α-SMA and COL1A2 expression, and inhibited the TGF-β1/Smad signaling pathway. HQD suppressed the proliferation and activation of HSCs. HQD increased miR-663a expression and decreased lnc-C18orf26-1 expression in HSCs. Further studies showed that HQD inhibited the expression of COL1A2, α-SMA, TGF-β1, TGF-β type I receptor (TGF-βRI) and phosphorylated Smad2 (p-Smad2) in HSCs, and these effects were reversed by miR-663a inhibitor treatment.@*CONCLUSION@#Our study identified lnc-C18orf26-1 and miR-663a as promising therapeutic targets for hepatic fibrosis. HQD inhibits HSC proliferation and activation at least partially by regulating the lnc-C18orf26-1/miR-663a/TGF-β1/TGF-βRI/p-Smad2 axis.
Subject(s)
Humans , Transforming Growth Factor beta/pharmacology , Transforming Growth Factor beta1/metabolism , RNA, Long Noncoding/pharmacology , Drugs, Chinese Herbal/pharmacology , MicroRNAs/genetics , Hepatic Stellate Cells/pathology , Liver Cirrhosis/metabolism , Cell Proliferation , Transforming Growth Factors/pharmacologyABSTRACT
Nonobstructive azoospermia (NOA) is a severe condition in infertile men, and increasing numbers of causative genes have been identified during the last few decades. Although certain causative genes can explain the presence of NOA in some patients, a proportion of NOA patients remain to be addressed. This study aimed to investigate potential high-risk genes associated with spermatogenesis in idiopathic NOA patients by whole-exome sequencing. Whole-exome sequencing was performed in 46 male patients diagnosed with NOA. First, screening was performed for 119 genes known to be related to male infertility. Next, further screening was performed to determine potential high-risk causative genes for NOA by comparisons with 68 healthy male controls. Finally, risk genes with high/specific expression in the testes were selected and their expression fluctuations during spermatogenesis were graphed. The frequency of cystic fibrosis transmembrane conductance regulator (CFTR) gene pathogenic variant carriers was higher in the NOA patients compared with the healthy controls. Potential risk genes that may be causes of NOA were identified, including seven genes that were highly/specifically expressed in the testes. Four risk genes previously reported to be involved in spermatogenesis (MutS homolog 5 [MSH5], cilia- and flagella-associated protein 54 [CFAP54], MAP7 domain containing 3 [MAP7D3], and coiled-coil domain containing 33 [CCDC33]) and three novel risk genes (coiled-coil domain containing 168 [CCDC168], chromosome 16 open reading frame 96 [C16orf96], and serine protease 48 [PRSS48]) were identified to be highly or specifically expressed in the testes and significantly different in the 46 NOA patients compared with 68 healthy controls. This study on clinical NOA patients provides further evidence for the four previously reported risk genes. The present findings pave the way for further functional investigations and provide candidate risk genes for genetic diagnosis of NOA.
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Humans , Male , Azoospermia/pathology , East Asian People , Exome Sequencing , Mutation , Proteins/geneticsABSTRACT
This paper aimed to study the effect of Dalbergia cochinchinensis heartwood on plasma endogenous metabolites in rats with ligation of the left anterior descending coronary artery, and to analyze the mechanism of D. cochinchinensis heartwood in improving acute myocardial ischemic injury. The stability and consistency of the components in the D. cochinchinensis heartwood were verified by the establishment of fingerprint, and 30 male SD rats were randomly divided into a sham group, a model group, and a D. cochinchinensis heartwood(6 g·kg~(-1)) group, with 10 rats in each group. The sham group only opened the chest without ligation, while the other groups established the model of ligation. Ten days after administration, the hearts were taken for hematoxylin-eosin(HE) staining, and the content of heart injury indexes in the plasma creatine kinase isoenzyme(CK-MB) and lactate dehydrogenase(LDH), energy metabolism-related index glucose(Glu) content, and vascular endothelial function index nitric oxide(NO) was determined. The endogenous metabolites were detected by ultra-high-performance liquid chromatography-time-of-flight-mass spectrometry(UPLC-Q-TOF-MS). The results showed that the D. cochinchinensis heartwood reduced the content of CK-MB and LDH in the plasma of rats to relieve myocardial injury, reduced the content of Glu in the plasma, improved myocardial energy metabolism, increased the content of NO, cured the vascular endothelial injury, and promoted vasodilation. D. cochinchinensis heartwood improved the increase of intercellular space, myocardial inflammatory cell infiltration, and myofilament rupture caused by ligation of the left anterior descending coronary artery. The metabolomic study showed that the content of 26 metabolites in the plasma of rats in the model group increased significantly, while the content of 27 metabolites decreased significantly. Twenty metabolites were significantly adjusted after the administration of D. cochinchinensis heartwood. D. cochinchinensis heartwood can significantly adjust the metabolic abnormality in rats with ligation of the left anterior descending coronary artery, and its mechanism may be related to the regulation of cardiac energy metabolism, NO production, and inflammation. The results provide a corresponding basis for further explaining the effect of D. cochinchinensis on the acute myocardial injury.
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Male , Animals , Rats , Rats, Sprague-Dawley , Dalbergia , Myocardial Ischemia , Metabolomics , Heart , Heart Injuries , Creatine Kinase, MB FormABSTRACT
OBJECTIVE@#This study investigated the effects of bis (2-butoxyethyl) phthalate (BBOP) on the onset of male puberty by affecting Leydig cell development in rats.@*METHODS@#Thirty 35-day-old male Sprague-Dawley rats were randomly allocated to five groups mg/kg bw per day that were gavaged for 21 days with BBOP at 0, 10, 100, 250, or 500 mg/kg bw per day. The hormone profiles; Leydig cell morphological metrics; mRNA and protein levels; oxidative stress; and AKT, mTOR, ERK1/2, and GSK3β pathways were assessed.@*RESULTS@#BBOP at 250 and/or 500 mg/kg bw per day decreased serum testosterone, luteinizing hormone, and follicle-stimulating hormone levels mg/kg bw per day (P < 0.05). BBOP at 500 mg/kg bw per day decreased Leydig cell number mg/kg bw per day and downregulated Cyp11a1, Insl3, Hsd11b1, and Dhh in the testes, and Lhb and Fshb mRNAs in the pituitary gland (P < 0.05). The malondialdehyde content in the testis significantly increased, while Sod1 and Sod2 mRNAs were markedly down-regulated, by BBOP treatment at 250-500 mg/kg bw per day (P < 0.05). Furthermore, BBOP at 500 mg/kg bw per day decreased AKT1/AKT2, mTOR, and ERK1/2 phosphorylation, and GSK3β and SIRT1 levels mg/kg bw per day (P < 0.05). Finally, BBOP at 100 or 500 μmol/L induced ROS and apoptosis in Leydig cells after 24 h of treatment in vitro (P < 0.05).@*CONCLUSION@#BBOP delays puberty onset by increasing oxidative stress and apoptosis in Leydig cells in rats.@*UNLABELLED@#The graphical abstract is available on the website www.besjournal.com.
Subject(s)
Rats , Male , Animals , Leydig Cells/metabolism , Testosterone , Glycogen Synthase Kinase 3 beta/pharmacology , Rats, Sprague-Dawley , Sexual Maturation , Testis , Oxidative Stress , TOR Serine-Threonine Kinases/metabolism , ApoptosisABSTRACT
BACKGROUND@#Vaccination against coronavirus disease 2019 (COVID-19) has become the primary approach in the fight against the spread of COVID-19. Studies have shown that vaccination against COVID-19 has adverse effects, particularly on human reproductive health, despite the fact that vaccination rates are still on the rise. However, few studies have reported whether vaccination affects the outcome of in vitro fertilization-embryo transfer (IVF-ET) or not. In this study, we compared the outcome of IVF-ET and the development of follicles and embryos between vaccinated and unvaccinated groups.@*METHODS@#A single-center retrospective cohort study of 10,541 in vitro fertilization (IVF) cycles was conducted from June 2020 to August 2021. 835 IVF cycles with a history of vaccination against COVID-19 and 1670 IVF cycles that served as negative controls were selected and analyzed utilizing the Matchlt package of R software ( http://www.R-project.org/ ) and the nearest neighbor matching algorithm for propensity-matched analysis at a 1:2 ratio.@*RESULTS@#The number of oocytes collected in the vaccinated group and the unvaccinated group were 8.00 (0, 40.00) and 9.00 (0, 77.00) ( P = 0.073) and the good-quality embryo rates of the two groups were 0.56±0.32 and 0.56±0.31 averagely ( P = 0.964). Clinical pregnancy rates for the vaccinated group and unvaccinated group were 42.4% (155/366) and 40.2% (328/816) ( P = 0.486) and biochemical pregnancy rates were 7.1% (26/366) and 8.7% (71/816) ( P = 0.355). Two other factors were analyzed in this study; vaccination among different genders and different types (inactivated vaccine or recombinant adenovirus vaccine) showed no statistically significant effect on the above outcomes.@*CONCLUSIONS@#In our findings, vaccination against COVID-19 showed no statistically significant effect on the outcomes of IVF-ET and the development of follicles and embryos, nor did the gender of the vaccinated person or the formulation of vaccines show significant effects.
Subject(s)
Pregnancy , Humans , Female , Male , Retrospective Studies , COVID-19/prevention & control , Embryo Transfer , Fertilization in Vitro , Pregnancy Rate , VaccinationABSTRACT
Osteoarthritis (OA) is one of the most common chronic diseases in the world. However, current treatment modalities mainly relieve pain and inhibit cartilage degradation, but do not promote cartilage regeneration. In this study, we show that G protein-coupled receptor class C group 5 member B (GPRC5B), an orphan G-protein-couple receptor, not only inhibits cartilage degradation, but also increases cartilage regeneration and thereby is protective against OA. We observed that Gprc5b deficient chondrocytes had an upregulation of cartilage catabolic gene expression, along with downregulation of anabolic genes in vitro. Furthermore, mice deficient in Gprc5b displayed a more severe OA phenotype in the destabilization of the medial meniscus (DMM) induced OA mouse model, with upregulation of cartilage catabolic factors and downregulation of anabolic factors, consistent with our in vitro findings. Overexpression of Gprc5b by lentiviral vectors alleviated the cartilage degeneration in DMM-induced OA mouse model by inhibiting cartilage degradation and promoting regeneration. We also assessed the molecular mechanisms downstream of Gprc5b that may mediate these observed effects and identify the role of protein kinase B (AKT)-mammalian target of rapamycin (mTOR)-autophagy signaling pathway. Thus, we demonstrate an integral role of GPRC5B in OA pathogenesis, and activation of GPRC5B has the potential in preventing the progression of OA.
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BACKGROUND@#Programmed cell death protein 1 (PD-1) combined with platinum containing dual drug chemotherapy is a new adjuvant treatment option for operable stage III non-small cell lung cancer (NSCLC), and the quality assurance of clinical trials of related drugs plays a crucial role in the results of the clinical trials. This study aims to explore the impact of adverse events (AEs) supervision on reducing treatment-related AEs in patients.@*METHODS@#66 NSCLC patients admitted to Shanghai Chest Hospital from July 2020 to October 2021 were prospectively collected. All the patients received 3 cycles of neoadjuvant treatment of Camrelizumab in combination with Docetaxel and Cisplatin. 4 weeks-6 weeks after neoadjuvant therapy, the patients accepted surgical treatment. One cycle of postoperative adjuvant treatment was given within 30 days after surgery, and 3 weeks after the completion of postoperative adjuvant treatment, Camrelizumab consolidation treatment was intiated, with a total of 13 cycles. The quality of life-C30 (QoL-C30) was used to measure patients' quality of life and the occurrence of AEs was monitored.@*RESULTS@#The overall safety is good, with a total of 300 AEs occurring in 66 patients, including 282 cases of grade 1-2 AEs and 18 cases of grades 3-4 AEs. The most common grades 3-4 AEs associated with PD-1 antibodies occurred in 6 cases (9.1%). Neoadjuvant therapy supervision can lead to a decrease in patients' QOL-C30 scores (P<0.05) and an improvement in their quality of life.@*CONCLUSIONS@#Camrelizumab combined with Docetaxel and Cisplatin can be used as a new adjuvant treatment for operable stage III NSCLC. Through the observation and control of AEs, treatment measures can be taken in time to reduce further complications, ensure patient' safety, and ensure the authenticity, scientificity and reliability of clinical trial data.
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Humans , Carcinoma, Non-Small-Cell Lung , China , Cisplatin , Docetaxel , Lung Neoplasms , Neoadjuvant Therapy , Programmed Cell Death 1 Receptor , Quality of Life , Reproducibility of Results , Prospective StudiesABSTRACT
This study aims to investigate the efficacy and possible mechanism of Liuwei Dihuang Pills in the treatment of diminished ovarian reserve(DOR) by using proteomic techniques. Firstly, cyclophosphamide(60 mg·kg~(-1)) combined with busulfan(6 mg·kg~(-1)) was injected intraperitoneally to establish the mouse model of DOR. After drug injection, the mice were continuously observed and the success of modeling was evaluated by the disturbance of the estrous cycle. After successful modeling, the mice were administrated with the suspension of Liuwei Dihuang Pills by gavage for 28 days. At the end of the gavage, four female mice were selected and caged together with males at a ratio of 2∶1 for the determination of the pregnancy rate. Blood and ovary samples were collected from the remaining mice on the next day after the end of gavage. Hematoxylin-eosin(HE) staining and transmission electron microscopy(TEM) were then employed to observe the morphological and ultrastructural changes in the ovaries. The serum levels of hormones and oxidation indicators were measured by enzyme-linked immunosorbent assay. Quantitative proteomics techniques were used to compare the ovarian protein expression before and after modeling and before and after the intervention with Liuwei Dihuang Pills. The results showed that Liuwei Dihuang Pills regulated the estrous cycle of DOR mice, elevated the serum levels of hormones and anti-oxidation indicators, promoted follicle development, protected the mitochondrial morphology of ovarian granulosa cells, and increased the litter size and survival of DOR mice. Furthermore, Liuwei Dihuang Pills negatively regulated the expression of 12 differentially expressed proteins associated with DOR, which were mainly involved in lipid catabolism, inflammatory response, immune regulation, and coenzyme biosynthesis. These differentially expressed proteins were significantly enriched in sphingolipid metabolism, arachidonic acid metabolism, ribosomes, ferroptosis, and cGMP-PKG signaling pathway. In summary, the occurrence of DOR and the treatment of DOR with Liuwei Dihuang Pills are associated with multiple biological pathways, mainly including oxidative stress response, inflammatory response, and immune regulation. "Mitochondria-oxidative stress-apoptosis" is the key to the treatment of DOR by Liuwei Dihuang Pills. YY1 and CYP4F3 may be the key upstream targets that trigger mitochondrial dysfunction and ROS accumulation, and the metabolism of arachidonic acid is the main signaling pathway of drug action.
Subject(s)
Female , Male , Pregnancy , Animals , Mice , Arachidonic Acid , Ovarian Reserve , Proteomics , Ovary , Lipid MetabolismABSTRACT
Objective: To investigate the early effect and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with a 10-day decitabine-containing conditioning regimen in the treatment of acute myeloid leukemia (AML) /myelodysplastic syndrome (MDS) . Methods: From April 2021 to May 2022, 31 AML/MDS patients who received allo-HSCT with a 10-day decitabine-containing conditioning regimen were analyzed. Results: AML (n=10), MDS-AML (n=6), CMML-AML (n=1), and MDS (n=14) were identified in 31 patients, 16 males, and 15 females, with a median age of 41 (20-55) yr. Neutrophils and platelets were successfully implanted in 31 patients (100%), with a median implantation duration of 12 (9-30) and 14 (9-42) days, respectively. During the preconditioning period, 16 patients (51.6%) developed oral mucositis, with 15 cases of Ⅰ/Ⅱ grade (48.4%) and one case of Ⅲ grade (3.2%). After transplantation, 13 patients (41.9%) developed CMV viremia, six patients (19.4%) developed hemorrhagic cystitis, and four patients (12.9%) developed a local infection. The median time of acute graft versus host disease (aGVHD) following transplantation was 33 (12-111) days. The cumulative incidence of aGVHD and Ⅲ/Ⅳ grade aGVHD was 41.9% (95% CI 26.9%-61.0%) and 22.9% (95% CI 13.5%-47.5%), respectively. There was no severe cGVHD, and mild and moderate chronic GVHD (cGVHD) incidence was 23.5% (95% CI 12.1%-43.6%). As of November 30, 2022, only one of the 31 patients had relapsed, with a 1-yr cumulative relapse rate (CIR) of 3.2% (95% CI 0.5%-20.7%). There was only one relapse patient death and no non-relapse deaths. The 1-yr overall survival (OS) and disease-free survival (DFS) rates were 92.9% (95% CI 80.3%-100%) and 96.8% (95% CI 90.8%-100%), respectively. Conclusions: A 10-day decitabine-containing conditioning regimen for allo-HSCT reduced relapse and was safe and feasible in treating AML/MDS.
Subject(s)
Male , Female , Humans , Decitabine , Myelodysplastic Syndromes/therapy , Leukemia, Myeloid, Acute/complications , Disease-Free Survival , Hematopoietic Stem Cell Transplantation/adverse effects , Recurrence , Chronic Disease , Graft vs Host Disease/etiology , Transplantation Conditioning/adverse effects , Bronchiolitis Obliterans Syndrome , Retrospective StudiesABSTRACT
OBJECTIVES@#To analyze the gross pathological data of sudden cardiac death (SCD) with different causes, to provide data support for the identification of sudden cardiac death with unknown causes.@*METHODS@#A total of 167 adult SCD cases in the archive of the Forensic Expertise Institute of Nanjing Medical University from 2010 to 2020 were collected. The gross pathological data of SCD cases were summarized and the characteristics of different causes of death were statistically analyzed.@*RESULTS@#The ratio of male to female SCD cases was 3.4∶1. Coronary heart disease was the leading cause of SCD, and mainly distributed in people over 40 years old. SCD caused by myocarditis was mainly distributed in young people and the mean age of death was (34.00±9.55) years. By analyzing the differences in cardiac pathological parameters of SCD with different causes, it was found that the aortic valve circumference was significantly dilated in the SCD caused by aortic aneurysm or dissection (P<0.05). The heart weight of SCD caused by aortic aneurysm or dissection and combined factors was greater, and both pulmonary and tricuspid valvular rings were dilated in the SCD caused by combined factors in adult males (P<0.05).@*CONCLUSIONS@#Various gross pathological measures of SCD with different causes are different, which has reference value in the cause of death identification of SCD.
Subject(s)
Humans , Adult , Male , Female , Adolescent , Young Adult , Death, Sudden, Cardiac/pathology , Coronary Disease , Heart , Forensic Medicine , AutopsyABSTRACT
Objective To analyze the epidemiological characteristics and risk factors of bronchiectasis in patients with chronic obstructive pulmonary disease (COPD) in Suining area, and to provide theoretical basis for COPD prevention and treatment of bronchiectasis. Methods A total of 582 patients with ACUTE exacerbation of COPD (AECOPD) admitted to grade A Hospitals in Suining area from 2019 to 2020 were selected as the investigation objects. According to whether the patients had bronchiectasis, they were divided into control group (without bronchiectasis, n=485) and observation group (with bronchiectasis, n=97). The risk factors of bronchiectasis in COPD patients were analyzed by univariate analysis and logistic regression. The clinical data of the two groups were compared, including age, sex, whether there were other diseases, respiratory tract infection, proportion of purpuric sputum, colonization rate of Pseudomonas aeruginosa. Results Of 16.84% (49/291) AECOPD patients occurred Bronchiectasis. The colonization rate of Pseudomonas aeruginosa in observation group was significantly higher than that in control group (P<0.05). The values of FVC and FEV1/FVC in observation group were significantly lower than those in control group (P<0.05). The levels of serum CRP and PCT in the observation group were significantly higher than those in the control group (P<0.05). Male (OR=2.515), high proportion of GOLD grade III/IV (OR=3.654), smoking (OR=3.472), diabetes (OR=3.829) and bacterial infection (OR=4.159) were independent risk factors for bronchiectasis in COPD patients (P<0.05). Conclusion COPD patients in Suining area have a high risk of bronchiectasis.The lung function was declined significantly.It has a high colonization rate of Pseudomonas aeruginosa. Patients who are male, have a high proportion of GOLD class III/IV, smoke, have diabetes, and have bacterial infections should be given interventions that can reduce the risk of bronchiectasis in COPD patients.
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Rosacea is a chronic inflammatory dermatosis mostly occurring on the central face, and its pathogenesis is still unclear. Currently, drug treatment is the first-line therapy for rosacea. In recent years, photoelectric therapy has showed a favorable therapeutic effect on rosacea by selective photothermolysis. This review summarizes latest advances in photoelectric therapy for rosacea.
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The clinical data of a patient with mitochondrial diabetes mellitus complicated with hypopituitarism were analyzed, the patient′s mitochondrial gene was detected by microarray capture high-throughput sequencing, and the related domestic and foreign literature was reviewed and analyzed. The results showed that the patient had m. 3243 A>G variant on MT-TL1 gene and the clinical features were consistent with mitochondrial diabetes mellitus and hypopituitarism.
ABSTRACT
Objective:To investigate the relationship between ALDH2 rs671 gene polymorphism and body fat content in Chinese Han population.Methods:It was a cross-sectional study. A total of 3 943 Chinese Han people were selected for physical examination in the Department of Health Medicine in the Second Medical Center of Chinese PLA General Hospital from January 2017 to January 2020, including 2 749 males and 1 194 females; the average age was (48.12±7.98) years. The research subjects were divided into obesity group and non-obesity group according to their body fat rate. The basic information including age, gender, disease history, height, weight, body fat content and blood samples were collected; the ALDH2 rs671 gene polymorphism was detected. Genotype and allele frequencies were compared between groups by using χ2 test. The comparison of clinical data between different genotypes was conducted by using one-way analysis of variance. The correlation between various indicators, lifestyle and genotype was analyzed by using a logistic regression model. Results:The distribution of ALDH2 rs671 genotype was wild genotype GG (68.6%), heterozygous mutant genotype GL (28.7%) and homozygous mutant genotype LL (2.7%). In terms of baseline characteristics, there were significant differences in male (67.5% vs 71.3%), body mass index (BMI, (23.12±2.64) kg/m 2 vs (27.10±2.75) kg/m 2), genotype distribution (GG 65.6% vs 70.6%), drinking history (64.4% vs 68.8%), history of hypertension (18.7% vs 36.9%), coronary heart disease (3.7% vs 5.6%) and diabetes (9.7% vs 15.0%) between the obesity and non-obesity group (all P<0.05). Multifactor logistic regression showed that ALDH2-GG genotype ( OR=1.386, 95% CI: 1.078-1.782), age ( OR=1.051, 95% CI: 1.035-1.068), and BMI ( OR=2.182, 95% CI: 2.043-2.331) were risk factors for obesity differentiated by body fat percentage, and male ( OR=0.175, 95% CI: 0.123-0.250) was protective factor (all, P<0.05). Conclusion:ALDH2 rs671 polymorphism is related to body fat content. The risk of excessive body fat content in individuals with GG genotype is significantly increased.