Efficacy of exercise rehabilitation for managing patients with Alzheimer's disease

Alzheimer's disease(AD) is a progressive and degenerative neurological disease characterized by the deterioration of cognitive functions. While a definitive cure and optimal medication to impede disease progression are currently unavailable, a plethora of studies have highlighted the potential advantages of exercise rehabilitation for managing this condition. Those studies show that exercise rehabilitation can enhance cognitive function and improve the quality of life for individuals affected by AD. Therefore, exercise rehabilitation has been regarded as one of the most important strategies for managing patients with AD. Herein, we provide a comprehensive analysis of the currently available findings on exercise rehabilitation in patients with AD, with a focus on the exercise types which have shown efficacy when implemented alone or combined with other treatment methods, as well as the potential mechanisms underlying these positive effects. Specifically, we explain how exercise may improve the brain microenvironment and neuronal plasticity. In conclusion, exercise is a cost-effective intervention to enhance cognitive performance and improve quality of life in patients with mild to moderate cognitive dysfunction. Therefore, it can potentially become both a physical activity and a tailored intervention. This review may aid the development of more effective and individualized treatment strategies to address the challenges imposed by this debilitating disease, especially in low-and middle-income countries.

Preclinical evaluation of cyclophosphamide and fludarabine combined with CD19 CAR-T in the treatment of B-cell hematologic malignancies in vivo

Background:Chimeric antigen receptor T(CAR-T)cell therapy has achieved marked therapeutic success in ameliorating hematological malignancies.However,there is an extant void in the clinical guidelines concerning the most effective chemotherapy regimen prior to chimeric antigen receptor T(CAR-T)cell therapy,as well as the optimal timing for CAR-T cell infusion post-chemotherapy.Materials and Methods:We employed cell-derived tumor xenograft(CDX)murine models to delineate the optimal pre-conditioning chemotherapy regimen and timing for CAR-T cell treatment.Furthermore,transcriptome sequencing was implemented to identify the therapeutic targets and elucidate the underlying mechanisms governing the treatment regimen.Results:Our preclinical in vivo evaluation determined that a combination of cyclophosphamide and fludarabine,followed by the infusion of CD19 CAR-T cells five days subsequent to the chemotherapy,exerts the most efficacious therapeutic effect in B-cell hematological malignancies.Concurrently,RNA-seq data indicated that the therapeutic efficacy predominantly perturbs tumor cell metabolism,primarily through the inhibition of key mitochondrial targets,such as C-Jun Kinase enzyme(C-JUN).Conclusion:In summary,the present study offers critical clinical guidance and serves as an authoritative reference for the deployment of CD19 CAR-T cell therapy in the treatment of B-cell hematological malignancies.

Systematic analysis of DNA polymerases as therapeutic targets in pan-cancers

Introduction:DNA polymerases are crucial for maintaining genome stability and influencing tumorigenesis.However,the clinical implications of DNA polymerases in tumorigenesis and their potential as anti-cancer therapy targets are not well understood.Methods:We conducted a systematic analysis using TCGA Pan-Cancer Atlas data and Gene Set Cancer Analysis results to examine the expression profiles of 15 DNA polymerases(POLYs)and their clinical correlations.We also evaluated the prognostic value of POLYs by analyzing their expression levels in relation to overall survival time(OS)using Kaplan-Meier survival curves.Additionally,we investigated the correlations between POLY expression and immune cells,DNA damage repair(DDR)pathways,and ubiquitination.Drug sensitivity analysis was performed to assess the relationship between POLY expression and drug response.Results:Our analysis revealed that 14 out of 15 POLYs exhibited significantly distinct expression patterns between tumor and normal samples across most cancer types,except for DNA nucleotidylexotransferase(DNTT).Specifically,POLD1 and POLE showed elevated expression in almost all cancers,while POLQ exhibited high expression levels in all cancer types.Some POLYs showed heightened expression in specific cancer subtypes,while others exhibited low expression.Kaplan-Meier survival curves demonstrated significant prognostic value of POLYs in multiple cancers,including PAAD,KIRC,and ACC.Cox analysis further validated these findings.Alteration patterns of POLYs varied significantly among different cancer types and were associated with poorer survival outcomes.Significant correlations were observed between the expression of POLY members and immune cells,DDR pathways,and ubiquitination.Drug sensitivity analysis indicated an inverse relationship between POLY expression and drug response.Conclusion:Our comprehensive study highlights the significant role of POLYs in cancer development and identifies them as promising prognostic and immunological biomarkers for various cancer types.Additionally,targeting POLYs therapeutically holds promise for tumor immunotherapy.

Histopathologic and Immunohistochemical Analysis of 66 Cases of Gastrointestinal Stromal Tumor

Background and Objective: To investigate the histopathological characteristics and immunohistochemistry of gastrointestinal stromal tumors (GIST). Immunohistochemistry (IHC) refers to the expression and meaning of CD117, DOG-1, CD34. Methods: Sixty-six gastrointestinal stromal tumor (GIST) samples with complete clinical data and definite clinicopathological diagnosis were collected from the Seventh Affiliated Hospital of Sun Yat-sen University from January 2019 to December 2022. Retrospective analysis was performed on the pathological data of 66 patients with GIST, and the histopathology and IHC were analyzed and summarized. Results: Among the 66 cases, 46, 14, 1, 5 were found in the stomach, small intestine, large intestine, and gastroenteral area. There were 45 cases (97%), 11 cases (79%), 1 case (100%), 5 cases (100%) in order of fusiform cell type. There were 1 case (3%), 2 cases (14%), 0 case, 0 case of upper dermatiform;Mixed type in 0 case, 1 case (7%), 0 case, 0 case;CD117 positive 66 cases (100%), DOG-1 positive 66 cases (100%), CD34 positive 61 cases (92%), CD117 and/or CD34 negative 5 cases (8%);CD34, CD117 and DOG-1 were negative simultaneously in 0 case. 19 cases (28%) were positive for SMA and 7 cases (11%) were positive for S-100. Conclusion: Fusiform cell type is the common type of GIST, followed by epithelioid type and mixed type, but the tumor sites are different, and the comparison cases are not completely the same. CD117, DOG-1 and CD34 are high surface in GIST, and the combination of SMA, S-100 and histomorphology can be used to diagnose most GIST.

Clinicopathologic Characteristics of Differentiated Thyroid Carcinoma in Children and Adolescents

Objective: To investigate the clinicopathologic features of differentiated thyroid carcinoma in children and adolescents. Methods: The clinical data of 7 children and adolescents with differentiated thyroid carcinoma were retrospectively analyzed, and the clinicopathologic features of differentiated thyroid carcinoma were analyzed by gender, tumor size and BRAF mutation. Results: There were 7 cases of thyroid papillary carcinoma. The mean age of patients was (18.71 ± 2.75), and the mean tumor diameter was (2.4 ± 1.04) cm. Lymph node metastasis rate was 100% (7/7). In children and adolescents, the lesion volume was larger, membrane invasion and vascular cancer thrombus were more likely to occur, BRAF mutation was less common, and the difference was statistically significant. Conclusion: Children and adolescents with differentiated thyroid carcinoma are more aggressive and prone to membrane invasion and lymph node metastasis;BRAF mutation is less common than in adults.

Differentiation of intrahepatic cholangiocarcinoma from hepatocellular carcinoma in high-risk patients: a predictive model using contrast-enhanced ultrasound

AIM To develop a contrast-enhanced ultrasound(CEUS)predictive model for distinguishing intrahepatic cholangiocarcinoma(ICC) from hepatocellular carcinoma(HCC) in high-risk patients.METHODS This retrospective study consisted of 88 consecutive high-risk patients with ICC and 88 high-risk patients with HCC selected by propensity score matching between May 2004 and July 2016. Patients were assigned to two groups, namely, a training set and validation set, at a 1:1 ratio. A CEUS score for diagnosing ICC was generated based on significant CEUS features. Then, a nomogram based on the CEUS score was developed, integrating the clinical data. The performance of the nomogram was then validated and compared with that of the LR-M of the CEUS Liver Imaging Reporting and Data System(LI-RADS).RESULTS The most useful CEUS features for ICC were as follows: rim enhancement(64.5%), early washout(91.9%), intratumoral vein(58.1%), obscure boundary of intratumoral non-enhanced area(64.5%), and marked washout(61.3%, all P < 0.05). In the validation set, the area under the curve(AUC) of the CEUS score(AUC = 0.953) for differentiation between ICC and HCC was improved compared to the LI-RADS(AUC = 0.742)(P < 0.001). When clinical data were added, the CEUS score nomogram was superior to the LI-RADS nomogram(AUC: 0.973 vs 0.916, P = 0.036, Net Reclassification Improvement: 0.077, Integrated Discrimination Index: 0.152). Subgroup analysis demonstrated that the CEUS score model was notably improved compared to the LIRADS in tumors smaller than 5.0 cm(P < 0.05) but not improved in tumors smaller than 3.0 cm(P > 0.05).CONCLUSION The CEUS predictive model for differentiation between ICC and HCC in high-risk patients had improved discrimination and clinical usefulness compared to the CEUS LIRADS.

Lingguizhugan decoction attenuates diet-induced obesity and hepatosteatosis via gut microbiota

BACKGROUND Obesity is a major risk factor for a variety of diseases such as diabetes,nonalcoholic fatty liver disease, and cardiovascular diseases. Restricting energy intake, or caloric restriction(CR), can reduce body weight and improve metabolic parameters in overweight or obese patients. We previously found that Lingguizhugan decoction(LZD) in combination with CR can effectively lower plasma lipid levels in patients with metabolic syndrome. However, the mechanism underlying CR and LZD treatment is still unclear.AIM To investigate whether CR and LZD improve metabolic parameters by modulating gut microbiota.METHODS We extracted the water-soluble components out of raw materials and dried as LZD extracts. Eight-week old male C57 BL/6 mice were treated with a 3-d treatment regime that included 24 h-fasting followed by gavage of LZD extracts for 2 consecutive days, followed by a normal diet(ND) ad libitum for 16 wk. To test the effects of gut microbiota on diet-induced obesity, 8-wk old male C57 BL/6 mice received fecal microbiota transplantation(FMT) from CR and LZD-treated mice every 3 d and were fed with high-fat diet(HFD) ad libitum for 16 wk.Control mice received either saline gavage or FMT from ND-fed mice receiving saline gavage as mentioned above. Body weight was monitored bi-weekly. Food consumption of each cage hosting five mice was recorded weekly. To monitor blood glucose, total cholesterol, and total triglycerides, blood samples were collected via submandibular bleeding after 6 h fasting. Oxygen consumption rate was monitored with metabolic cages. Feces were collected, and fecal DNA was extracted. Profiles of gut microbiota were mapped by metagenomic sequencing.RESULTS We found that CR and LZD treatment significantly reduced the body weight of mice fed with ND(28.71 ± 0.29 vs 28.05 ± 0.15, P < 0.05), but did not affect plasma total cholesterol or total triglyceride levels. We then transplanted the fecal microbiota collected from CR and LZD-treated mice under ND feeding to HFDfed mice. Intriguingly, transplanting the mice with fecal microbiota from CR and LZD-treated mice potently reduced body weight(44.95 ± 1.02 vs 40.53 ± 0.97, P <0.001). FMT also reduced HFD-induced hepatosteatosis, in addition to improved glycemic control. Mechanistic studies found that FMT increased OCR of the mice and suppressed the expression and protein abundance of lipogenic genes in the liver. Metagenomic analysis revealed that HFD drastically altered the profile of gut microbiota, and FMT modified the profile of the gut microbiota.CONCLUSION Our study suggests that CR and LZD improve metabolic parameters by modulating gut microbiota.

Expression of long non-coding RNAs in complete transection spinal cord injury: a transcriptomic analysis

Long non-coding RNAs(lncRNAs)are abundantly expressed in the central nervous system and exert a critical role in gene regulation via multiple biological processes.To uncover the functional significance and molecular mechanisms of lncRNAs in spinal cord injury(SCI),the expression signatures of lncRNAs were profiled using RNA sequencing(RNA-seq)technology in a Sprague-Dawley rat model of the 10th thoracic vertebra complete transection SCI.Results showed that 116 of 14,802 detected lncRNAs were differentially expressed,among which 16—including eight up-regulated(H19,Vof16,Hmox2-ps1,LOC100910973,Ybx1-ps3,Nnat,Gcgr,LOC680254)and eight down-regulated(Rmrp,Terc,Ngrn,Ppp2r2b,Cox6a2,Rpl37a-ps1,LOC360231,Rpph1)—demonstrated fold changes>2 in response to transection SCI.A subset of these RNA-seq results was validated by quantitative real-time PCR.The levels of 821 mRNAs were also significantly altered post-SCI;592 mRNAs were up-regulated and 229 mRNAs were down-regulated by more than 2-fold.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses showed that differentially expressed mRNAs were related to GO biological processes and molecular functions such as injury and inflammation response,wound repair,and apoptosis,and were significantly enriched in 15 KEGG pathways,including cell phagocytosis,tumor necrosis factor alpha pathway,and leukocyte migration.Our results reveal the expression profiles of lncRNAs and mRNAs in the rat spinal cord of a complete transection model,and these differentially expressed lncRNAs and mRNAs represent potential novel targets for SCI treatment.We suggest that lncRNAs may play an important role in the early immuno-inflammatory response after spinal cord injury.This study was approved by the Administration Committee of Experimental Animals,Guangdong Province,China.

Gut microbiota as a target for prevention and treatment of type 2 diabetes:Mechanisms and dietary natural products

Type 2 diabetes mellitus(T2DM)is among the most remarkable public health concerns globally.Accumulating research evidence documents that alteration of gut microbiota has an indispensable role in the onset and progression of obesity and T2DM.A reduced microbial diversity is linked to insulin resistance and energy metabolism,especially for the rise of the Firmicutes/Bacteroidetes ratio.Changes in metabolites followed by the gut dysbacteriosis are linked to the presence of T2DM.Moreover,endotoxin leakage and gut permeability caused by gut dysbacteriosis is more of a trigger for the onset and progression of T2DM.Research documents that natural products are remarkable arsenals of bioactive agents for the discovery of anti-T2DM drugs.Many studies have elucidated that the possible mechanisms of the anti-T2DM effects of natural products are remarkably linked to its regulation on the composition of gut microflora and the successive changes in metabolites directly or indirectly.This review presents a brief overview of the gut microbiota in T2DM and several relevant mechanisms,including short-chain fatty acids,biosynthesis and metabolism of branched-chain fatty acids,trimethylamine N-oxide,bile acid signaling,endotoxin leakage,and gut permeability,and describes how dietary natural products can improve T2DM via the gut microbiota.

Current application and future directions of photobiomodulation in central nervous diseases

Photobiomodulation using light in the red or near-infrared region is an innovative treatment strategy for a wide range of neurological and psychological conditions.Photobiomodulation can promote neurogenesis and elicit anti-apoptotic,antiinflammatory and antioxidative responses.Its therapeutic effects have been demonstrated in studies on neurological diseases,peripheral nerve injuries,pain relief and wound healing.We conducted a comprehensive literature review of the application of photobiomodulation in patients with central nervous system diseases in February 2019.The NCBI PubMed database,EMBASE database,Cochrane Library and ScienceDirect database were searched.We reviewed 95 papers and analyzed.Photobiomodulation has wide applicability in the treatment of stroke,traumatic brain injury,Parkinson’s disease,Alzheimer’s disease,major depressive disorder,and other diseases.Our analysis provides preliminary evidence that PBM is an effective therapeutic tool for the treatment of central nervous system diseases.However,additional studies with adequate sample size are needed to optimize treatment parameters.

New insights into the immunologic role of oligodendrocyte lineage cells in demyelination diseases

Oligodendrocyte lineage cells(OL-lineage cells)are a cell population that are crucial for mammalian central nervous system(CNS)myelination.OL-lineage cells go through developmental stages,initially differentiating into oligodendrocyte precursor cells(OPCs),before becoming immature oligodendrocytes,then mature oligodendrocytes(OLs).While the main function of cell lineage is in myelin formation,and increasing number of studies have turned to explore the immunological characteristics of these cells.Initially,these studies focused on discovering how OPCs and OLs are affected by the immune system,and then,how these immunological changes influence the myelination process.However,recent studies have uncovered another feature of OL-lineage cells in our immune systems.It would appear that OL-lineage cells also express immunological factors such as cytokines and chemokines in response to immune activation,and the expression of these factors changes under various pathologic conditions.Evidence suggests that OL-lineage cells actually modulate immune functions.Indeed,OL-lineage cells appear to play both"victim"and"agent"in the CNS which raises a number of questions.Here,we summarize immunologic changes in OL-lineage cells and their effects,as well as consider OL-lineage cell changes which influence immune cells under pathological conditions.We also describe some of the underlying mechanisms of these changes and their effects.Finally,we describe several studies which use OL-lineage cells as immunotherapeutic targets for demyelination diseases.

Proportion and characteristic of emmetropia in schoolchildren aged 6-11y:the Shenzhen elementary school eye study

AIM:To investigate the proportion and characteristic of emmetropia in schoolchildren aged 6-11,especially estimate the normal value of ocular biometric parameters of emmetropia.METHODS:A population-based cross-sectional study was conducted on children aged 6-11 y in Shenzhen.Totally,2386 schoolchildren from two primary schools were involved.The axial length(AL)and the corneal radius of curvature(CRC)were measured by partial coherence laser interferometry.Noncycloplegic refraction and refractive astigmatism(RA)was measured using autorefraction.The axial length-to-corneal radius of curvature ratio(AL/CRC),corneal astigmatism(CA)and spherical equivalent refraction(SER)were calculated.RESULTS:The proportion of emmetropia in elementary school students was 41.30%.This percentage decreased gradually from 6 to 11 years of age and decreased rapidly after 9 years of age.The mean and 95%CI of each parameter were provided for boys and girls aged 6 to 11 years of age with emmetropia according to each age group.The change trend of parameters of boys and girls are similar.After 7 years of age,the AL of non-emmetropia started to increase faster than that of emmetropia.The change trend of AL/CRC was the same as that of AL.The other parameters tend to be stable after 7 years of age.CONCLUSION:The age of 7-9 is an important period for the changes of refractive state and ocular biometric parameters of primary school students,and it is a special focus period for children myopia prevention.The normal value and variation of ocular biometric parameters of emmetropia can provide the basis for the clinical judgment of whether or not children’s ocular biometric parameters obtained by single measurement and changes obtained by multiple measurements are abnormal.

Functionalized Hydrogels for Articular Cartilage Tissue Engineering

Articular cartilage(AC)is an avascular and flexible connective tissue located on the bone surface in the diarthrodial joints.AC defects are common in the knees of young and physically active individuals.Because of the lack of suitable tissue-engineered artificial matrices,current therapies for AC defects,espe-cially full-thickness AC defects and osteochondral interfaces,fail to replace or regenerate damaged carti-lage adequately.With rapid research and development advancements in AC tissue engineering(ACTE),functionalized hydrogels have emerged as promising cartilage matrix substitutes because of their favor-able biomechanical properties,water content,swelling ability,cytocompatibility,biodegradability,and lubricating behaviors.They can be rationally designed and conveniently tuned to simulate the extracel-lular matrix of cartilage.This article briefly introduces the composition,structure,and function of AC and its defects,followed by a comprehensive review of the exquisite(bio)design and(bio)fabrication of func-tionalized hydrogels for AC repair.Finally,we summarize the challenges encountered in functionalized hydrogel-based strategies for ACTE both in vivo and in vitro and the future directions for clinical translation.

Relationship between Facet Joint Asymmetry and Adjacent Intervertebral Disc Degeneration in Lumbar Disc Herniation

Objective: To analyze the relationship between facet joint asymmetry and adjacent intervertebral disc degeneration in lumbar disc herniation. Methods: Fifty patients with L4/5 lumbar disc herniation were enrolled in the study. All patients underwent lumbar MRI examination, to compare the facet asymmetry of lumbar disc herniation and the degeneration of cartilage endplate and intervertebral disc of adjacent segments, and analyze the relationship between them. Results: There was no significant correlation between L4/5 facet asymmetry and L5/S1 intervertebral disc degeneration score and cartilage endplate degeneration score (P > 0.05). L4/5 facet asymmetry was significantly correlated with L3/4 disc degeneration score (P < 0.01), but not with cartilage endplate degeneration score (P > 0.05). Conclusion: There was a positive correlation between the facet joint angle of lumbar disc herniation and the degeneration of upper proximal segment intervertebral disc. Early correction of lumbar facet angle asymmetry can provide beneficial guidance for further prevention and treatment.

Feasibility of Transabdominal Real-time CDFI and HDFI Techniques for Fetal Pulmonary Vein Display in the First Trimester

Objective This study aimed to assess the feasibility and usefulness of transabdominal color Doppler flow imaging(CDFI)technology and the high-definition flow imaging(HDFI)technique in detecting fetal pulmonary veins(PVs)in the first trimester(11–13^(+6)weeks).Methods From December 2018 to October 2019,328 pregnant women with 328 normal singleton fetuses(crown-rump length:45–84 mm)who had undergone CDFI and HDFI scans for fetal heart and vessel examination were enrolled in this study.The cases were divided into three groups according to the gestational age:group A,11^(+0)−11^(+6)weeks;group B,12^(+0)−12^(+6)weeks;and group C,13^(+0)−13^(+6)weeks.Baseline sonograms and CDFI and HDFI images were analyzed by two senior radiologists independently and blindly.The abilities of CDFI and HDFI to display PVs were compared.Results Successful PV display rates via CDFI and HDFI were 2.3%and 68.2%(P<0.01),22.4%and 82.4%(P<0.01),41.5%and 91.2%(P<0.01)for group A,group B,and group C,respectively.The total successful display rates for the two methods were 28.9%(CDFI)and 84.8%(HDFI)(P<0.01).Conclusions The HDFI technique is more valuable than CDFI for detecting PVs in early pregnancy(11–13^(+6)weeks).HDFI can detect at least one PV in all cases and may be used to detect pulmonary venous anomalies early.

Hemoglobin Fukuoka caused unexpected hemoglobin A1c results: A case report

BACKGROUND Glycated hemoglobin(Hb)(HbA1c)is an indicator that is used to diagnose and monitor the treatment of diabetes.Many factors can affect the detection of HbA1c.One of the most important of these factors is the Hb variant.Here,we report a rare Hb variant and evaluate its effect on HbA1c.CASE SUMMARY A 35-year-old man was suspected of harboring an Hb variant following the measurement of HbA1c with the Variant II Turbo 2.0 Hb detection system during a routine examination.Subsequently,we used the Arkray HA-8160 and ARCHITECT c4000 system to reanalyze HbA1c.Finally,the Hb variant was detected with a Capillary2FP analyzer that operates on the principle of capillary electrophoresis.We also used gene sequencing to investigate the mutation site.The value of HbA1c detected with the Variant II Turbo 2.0 system was 52.7%.However,the Arkray HA-8160 system did not display a result while the ARCHITECT c16000 system showed a result of 5.4%.The Capillary2FP analyzer did not reveal any abnormal Hb zones.However,gene sequencing identified the presence of a mutation in the Hbβ2 chain[CD2(CAC>TAC),His>Tyr,HBB:c.7C>T];the genotype was Hb Fukuoka.CONCLUSION Hb variants could cause abnormal HbA1c results.For patients with Hb variants,different methods should be used to detect HbA1c.

Misdiagnosis of pancreatic metastasis from renal cell carcinoma:A case report

BACKGROUND Pancreatic metastases account for only a small proportion of all pancreatic malignancies.Isolated pancreatic metastasis from renal cell cancer(isPM-RCC)is extremely rare and may be difficult to differentiate from more common primary neoplasms.A history of nephrectomy is crucial for the diagnosis.CASE SUMMARY We report the case of a 64-year-old Asian man who was diagnosed with a mass in the pancreatic head using computed tomography.He had no related symptoms,and his medical history was unremarkable,except for unilateral nephrectomy performed to remove a“benign”tumor 19 years ago.All preoperative imaging findings suggested a diagnosis of pancreatic neuroendocrine tumor.However,ultrasound-guided biopsy revealed features of clear cell renal cell carcinoma(ccRCC).Re-examination of the specimen resected 19 years ago confirmed that he had a ccRCC.The pancreatic mass was resected and pathological examination confirmed isPM-RCC.CONCLUSION Misdiagnosis of isPM-RCC is common because of its rarity and the long interval from resection of the primary tumor and manifestation of the metastasis.The history of the previous surgery may be the only clue.

Association between serum cystatin C level and hemodynamically significant aortic stenosis: a prospective cohort study

BACKGROUND Cystatin C(CysC)is a cysteine protease inhibitor involved in proteins catabolism and plays an essential role in human vascular pathophysiology.CysC may also increase the risk of aortic stenosis(AS),but limited studies have reported on this association.This study aimed to investigate if elevated serum CysC levels are associated with hemodynamically significant AS.METHODS Serum CysC levels were estimated in 4,791 participants,samples were collected in 1990−1992.The study popula-tion was divided into quintile groups.Follow-up continued in 2011-2013 when participants returned for echocardiography exam-ination.Incidence of aortic valve disease(AVD)was ascertained by Doppler echocardiography through the end of 2013.AVD defined in hemodynamic progression was assessed and classified as aortic sclerosis,mild stenosis,and moderate-to-severe sten-osis.RESULTS Overall,a total of 4,791 participants(mean age:54.8±5.0 years,females:57.6%,blacks:8.2%)were included in this study.During a follow-up of 21 years,we identified 736 cases(15.4%)of aortic sclerosis,194 cases(4.0%)of mild stenosis,and 42 cases(0.7%)of moderate-to-severe stenosis.Compared with serum CysC levels within individual quintile groups,the odds ratio(OR)was per standard deviation associated with an increased incidence of AVD(OR=1.15,95%CI:1.05−1.26,P=0.002).CONCLUSIONS In this large population-based study,an increased serum CysC levels is independently associated with the incidence of hemodynamically significant AS.However,this association appears not to extend to patients with extremely high serum CysC levels and necessitate further investigation.

The Association between Expression of NK Cells and Prognosis of Patients with HBV Acute-on-Chronic Liver Failure in Advanced Phase

Acute-on-chronic liver failure (Acute-on-chronic liver failure, ACLF) is acute liver function decompensation on the basis of chronic liver disease. The progression of ACLF develops from advanced phase, plateau phase to remission phase. The pathophysiological basis of ACLF in different phases is various. In advanced phase, immune imbalance and systemic inflammatory reaction plays key roles. In this study, we try to assess the association between expression of NK cells and its receptors and prognosis of patients with ACLF in advanced phase. A total of 35 inpatients with HBV acute-on-chronic liver failure in advanced phase were recruited. They were divided into case group (n = 18) and control group (n = 17) according to whether the patients was dead in the 12 weeks. PBMC were detected for the frequency and expression of NK cell receptors by flow cytometric analysis. Our results demonstrated that patients who died had lower expression of NK cells and inhibitory receptor KIR3DL1, higher levels of FASL. During 12-week follow-up in those case alive, we found that NK cells increased, while expression of FASL decreased. High short-term mortality of ALCF was associated with NK cell, especially related to KIR3DL1 and FASL (PNK = 0.036, PKIR3DL1 = 0.0265, PFasL = 0.0008).

Tubular Carcinoma of the Breast: A Clinicopathological Analysis of Two Cases

Tubular Carcinoma (TC) of the breast, also known as tubular carcinoma or well-differentiated adenocarcinoma, is defined as a special type of breast cancer consisting of well-differentiated tubular structures with excellent prognosis by WHO (2019) pathological and genetic classification of breast neoplasms. Two cases of breast tubular carcinoma admitted to our hospital were reported. The relevant literature was reviewed and the clinical features, histological morphology (microscopic features and differential diagnosis), molecular changes and clinical prognosis were summarized.