The liver performs several vital functions such as metabolism,toxin removal,and glucose storage through the coordination of various cell types.With the recent breakthrough of the single-cell/single-nucleus RNAseq(sc/s...The liver performs several vital functions such as metabolism,toxin removal,and glucose storage through the coordination of various cell types.With the recent breakthrough of the single-cell/single-nucleus RNAseq(sc/snRNA-seq)techniques,there is a great opportunity to establish a reference cell map of the liver at single-cell resolution with transcriptome-wise features.In this study,we build a unified liver cell atlas uniLIVER(http://lifeome.net/database/uniliver)by integrative analysis of a large-scale sc/snRNA-seq data collection of normal human liver with 331,125 cells and 79 samples from 6 datasets.Moreover,we introduce LiverCT,a machine learning based method for mapping any query dataset to the liver reference map by introducing the definition of“variant”cellular states analogous to the sequence variants in genomic analysis.Applying LiverCT on liver cancer datasets,we find that the“deviated”states of T cells are highly correlated with the stress pathway activities in hepatocellular carcinoma,and the enrichments of tumor cells with the hepatocyte-cholangiocyte“intermediate”states significantly indicate poor prognosis.Besides,we find that the tumor cells of different patients have different zonation tendencies and this zonation tendency is also significantly associated with the prognosis.This reference atlas mapping framework can also be extended to any other tissues.展开更多
Hepatocellular carcinoma(HCC)is a leading cause of cancer-related mortality,and resistance to systemic therapies remains a significant clinical challenge.This study investigated the mechanisms by which metabolic repro...Hepatocellular carcinoma(HCC)is a leading cause of cancer-related mortality,and resistance to systemic therapies remains a significant clinical challenge.This study investigated the mechanisms by which metabolic reprogramming contributes to systemic treatment resistance in HCC.We established HCC cell lines with multidrug resistance characteristics and observed enhanced metabolic activity in these cells.Integrated multiomics analyses revealed hyperactive glucose‒lipid and glutathione metabolic pathways that play critical roles in supporting tumor cell proliferation and survival.We constructed a metabolic reprogramming atlas for HCC-resistant cells and identified aldo-keto reductase(Aldo-keto reductase family 1 Member B1,AKR1B1)as a key regulator of this reprogramming,which sustains drug resistance by regulating energy metabolism and enhancing stress tolerance.Importantly,AKR1B1 expression levels are closely associated with drug resistance and poor prognosis in HCC patients.The secretory nature of AKR1B1 not only underscores its predictive value but also facilitates the intercellular transmission of drug resistance.In terms of overcoming resistance,the AKR1B1 inhibitor epalrestat significantly mitigated drug resistance when it was used in combination with standard therapies.These findings underscore the importance of metabolic reprogramming in the development of HCC resistance.AKR1B1,a key enzyme that regulates metabolic reprogramming,has been identified as a potential biomarker and therapeutic target,providing new insights into overcoming resistance in HCC treatment.展开更多
Diagnosing Alzheimer’s disease(AD)in the early stage is challenging.Informative biomarkers can be of great value for population-based screening.Metabolomics studies have been used to find potential biomarkers,but com...Diagnosing Alzheimer’s disease(AD)in the early stage is challenging.Informative biomarkers can be of great value for population-based screening.Metabolomics studies have been used to find potential biomarkers,but commonly used tissue sources can be difficult to obtain.The objective of this study was to determine the potential utility of erythrocyte metabolite profiles in screening for AD.Unlike some commonly-used sources such as cerebrospinal fluid and brain tissue,erythrocytes are plentiful and easily accessed.Moreover,erythrocytes are metabolically active,a feature that distinguishes this sample source from other bodily fluids like plasma and urine.In this preliminary pilot study,the erythrocyte metabolomes of 10 histopathologically confirmed AD patients and 10 patients without AD(control(CTRL))were compared.Whole blood was collected post-mortem and erythrocytes were analyzed using ultraperformance liquid chromatography tandem mass spectrometry.Over 750 metabolites were identified in AD and CTRL erythrocytes.Seven were increased in AD while 24 were decreased(P<0.05).The majority of the metabolites increased in AD were associated with amino acid metabolism and all of the decreased metabolites were associated with lipid metabolism.Prominent among the potential biomarkers were 10 sphingolipid or sphingolipid-related species that were consistently decreased in AD patients.Sphingolipids have been previously implicated in AD and other neurological conditions.Furthermore,previous studies have shown that erythrocyte sphingolipid concentrations vary widely in normal,healthy adults.Together,these observations suggest that certain erythrocyte lipid phenotypes could be markers of risk for development of AD.展开更多
Purpose: To quantitate the normal level of the tear meniscus, and to determine whether it is an accurate diagnostic indicator of nasolacrimal drainage obstruction. Methods: We performed a retrospective, controlled, ca...Purpose: To quantitate the normal level of the tear meniscus, and to determine whether it is an accurate diagnostic indicator of nasolacrimal drainage obstruction. Methods: We performed a retrospective, controlled, case series study on patients evaluated from 2000 to 2002 for epiphora. The height of the tear meniscus was measured using the slit lamp by one experienced observer. Nasolacrimal outflow status was assessed by probing and irrigation. Patency on the nontearing eye was also confirmed by probing and irrigation, and the corresponding tear meniscus levels comprised one control group (59 sides of 62 patients). Tear meniscus levels in patients with ptosis or dermatochalasis without epiphora comprised the second control group (78 sides of 39 patients). The 2 control groups were combined to determine the normal tear meniscus level and ratio between the two sides. The control tear meniscus levels and ratios in patients without epiphora were compared with the tear meniscus levels and ratios in patients with nasolacrimal obstruction (65 sides of 62 patients). Results: The 2 control groups examined did not statistically differ with respect to tear meniscus height (P=0.06). The control median tear meniscus level (0.2mm) significantly differed from the obstructed median tear meniscus level (0.6 mm) (P< 0.0001). The control median ratio between the two sides (1.0) significantly differed from the obstructed ratio (2.5) (P< 0.0001). The absolute tear meniscus level and the tear meniscus ratio were both accurate indicators of obstruction. The percent change in absolute tear meniscus level after lacrimal surgery was- 58.3% . Conclusions: To our knowledge, a quantitative analysis of the tear meniscus height has not been previously documented in the literature. Patients with nasolacrimal system stenosis or obstruction have elevated tear meniscus levels and ratios relative to control subjects. The absolute tear meniscus level and ratio tests are excellent diagnostic indicators of nasolacrimal obstruction and its resolution after successful lacrimal surgery.展开更多
Objective: To investigate the law of age-related changes of insulin-like growth factor-1 (IGF-1) expression of rat thyroid cells cultured in vitro. Methods: Rat thyroid of different age (10, 45, 65, 100, 150 weeks) wa...Objective: To investigate the law of age-related changes of insulin-like growth factor-1 (IGF-1) expression of rat thyroid cells cultured in vitro. Methods: Rat thyroid of different age (10, 45, 65, 100, 150 weeks) was isolated and thyrocytes cultured. Total RNA was extracted in different rat age group when thyroid cells had been cultured for two weeks. mRNA IGF-1 expression was measured with reverse-transcription polymerase chain reaction( RT-PCR) in each group and compared. Results: Quantity of total RNA in thyroid cells decreased with ageing when the rat thyroid cells had been cultured for 2 weeks. There is significant difference among groups (P<0.05). Expression of IGF-1 mRNA could be detected in thyroid cells of different age cultured in vitro. Quantity of IGF-1 mRNA expression by RT-PCR analysis increased from 10 to 45 weeks old, and then decreased with ageing. Conclusion: Rat thyroid cells from different age cultured in vitro can express IGF-1 mRNA. Quantity of total RNA in thyroid cells cultured in vitro decreased with aging. IGF-1 mRNA expression was correlated to age (r=0.401, P<0.05).展开更多
This study assessed whether there was a scat tering spectral mar ker quantifiable by reflectance measurements that could indicate early development of hepatic steatosis in rats for potential applications to pre procur...This study assessed whether there was a scat tering spectral mar ker quantifiable by reflectance measurements that could indicate early development of hepatic steatosis in rats for potential applications to pre procurement organ evaluation.Sixteen rats were fed a methionine choline-deficient(MCD)diet and eight rats were fed a normal diet.Direct assessment of the liver parenchyma of rats in vivo was performed by percut aneous reflect ance spectroscopy using a single fiber probe at the beginning of diet-intake and arbitrary post-diet-intake times up to 11 weeks to render longitudinal comparison.Histological sampling of the liver over the duration of diet adm inistration was performed on two MCD diet treated rats and one control rat eutha-nized after reflectance spectroscopy measurement.The images of hematoxylin/eosin-stained liver specimens were analyzed morphometrically to evahuate the lipid size changes associated with the level of steatosis.The MCD-diet-treated group(n=16)had mild steatosis in seven rats,moderate in three rats,severe in six rats,and no other significant pathology.No control rats(n=8)developed hepatic steatosis.Among the parameters retrieved from per-SfS,only the scat tering power(can be either positive or negative)appeared to be statist ically diferent between MCD-treated and control livers.The scattering power for the 16 MCD-diet-treated livers at the time of euthanasia and presenting various levels of steatosis was 033±0.21,in comparison to 0.036±0.25 of the eight control livers(p=0.0189).When evaluated at days 12 and 13 combined,the scattering power of the 16 MCD-diet-treated livers was 032±0.17,in comparison to 0.10±0.11 of the eight control livers(p=0.0017).All of four MCD-treated livers harvested at days 12 and 13 presented mild steatosis with sub-micron size lipid droplets,even though none of the MCD-treated livers were sonogr aphically remarkable for fatty changes.The elevation of the scattering power may be a valuable marker indicating early hepatic steatosis before the steatosis is sonographically detectable.展开更多
Objectives: To examine the histopathologic features of iridectomy specimens from patients undergoing glaucoma surgery and to compare histologic abnormalities in a group of patients with a history of latanoprost therap...Objectives: To examine the histopathologic features of iridectomy specimens from patients undergoing glaucoma surgery and to compare histologic abnormalities in a group of patients with a history of latanoprost therapy with those in a group of patients who had no history of prostaglandin therapy (controls). Methods: Iridectomy specimens and patient history forms were submitted to the central Latanoprost Pathology Center. These were independently examined by 3 ophthalmic pathologists in a masked fashion. Specimens were evaluated for malignant, premalignant, and other changes including differences in levels of pigmentation, degrees of cellularity, inflammation, vascular abnormalities, and changes in the iris pigment epithelium. Results: Specimens were received from 449 patients with a history of latanoprost treatment and 142 patients who had no history of treatment with latanoprost or other prostaglandin analogues. No evidence of malignant or premalignant changes was found. In latanoprost- treated irides, the prevalence of iris freckles was higher (P=.001) than in control irides, as was the combined number of stromal fibroblasts and melanocytes (P < .001). In a subgroup of specimens received through June 2002, there was no significant difference in mean melanocyte counts (P=.35)- obtained by immunohistochemical staining techniques between the latanoprost- treated and control groups. Conclusions: These findings support previous studies indicating that latanoprost- in- duced eye color changes are due to an increased amount of melanin within the iris stromal melanocytes. The increased numbers of freckles may be a focal manifestation of this effect.展开更多
Objective: To review health-related quality of life (QOL) and associated issues and to describe a study investigating “ Child Health Questionnaire” (CHQ) scores in relationship to newborn screening (NBS) for cystic ...Objective: To review health-related quality of life (QOL) and associated issues and to describe a study investigating “ Child Health Questionnaire” (CHQ) scores in relationship to newborn screening (NBS) for cystic fibrosis (CF) and markers of disease severity. Methods: A total of 36 patients from 10-15.5 years old who were enrolled in the screened or control group of the Wisconsin CF Neonatal Screening Project completed the CHQ. Scale scores comprised the dependent variables. Independent variables included study group and measures of disease severity. Analyses included Fisher’ s exact, 2-sample Wilcoxon, and t tests. Results: QOL did not differ significantly between the screened and control groups for any of the scales. None of the comparisons of CHQ scale scores across measures of disease severity were significant in this small sample, but the CHQ and power were limiting. Conclusions: Our results did not demonstrate a benefit of CF NBS on QOL; however, the CHQ may not be adequately sensitive to QOL in children with CF with disease severity comparable to our sample. The Cystic Fibrosis Questionnaire, a recently validated CF-specific QOL measure for pediatric samples, is likely to provide a more informative evaluation of the effects of CF NBS on patients’ QOL.展开更多
Medical imaging is essential for the diagnosis and treatment of liver diseases,and the objective analysis of such images is vital for precision medicine.Integration of artificial intelligence(AI),particularly computer...Medical imaging is essential for the diagnosis and treatment of liver diseases,and the objective analysis of such images is vital for precision medicine.Integration of artificial intelligence(AI),particularly computer vision,into hepatology has seen considerable growth.This study conducts a bibliometric analysis to map the evolution,principal trends,and focal points of AI in liver disease imaging research.We conducted a comprehensive literature review using the Web of Science Core Collection and PubMed databases,spanning January 1990 to July 2023,with keywords related to liver diseases and AI in medical imaging.The search resulted in 3,629 documents,with a surge in publications after 2017.The United States and China led in terms of publication volume,with the former exhibiting higher H-index scores and citation counts.However,greater number of research institutions that contribute significantly to publications in the relevant fields are based in China.Keyword analysis revealed extensive research on liver fibrosis,hepatocellular carcinoma,cirrhosis,and fatty liver disease.Techniques such as image segmentation,classification,and registration are prevalent,meeting clinical needs like lesion detection and disease prognosis.Convolutional neural networks(CNNs),particularly U-Net models,are predominantly utilized.This review synthesizes the findings to guide future advancements in AI-assisted liver disease diagnosis and management.展开更多
Hepatocyte proliferation is essential for recovering liver function after injury. Inliver surgery, the mechanical stimulation induced by hemodynamic changes triggers vascularendothelial cells (VECs) to secrete large a...Hepatocyte proliferation is essential for recovering liver function after injury. Inliver surgery, the mechanical stimulation induced by hemodynamic changes triggers vascularendothelial cells (VECs) to secrete large amounts of cytokines that enhance hepatocyte proliferation and play a pivotal role in liver regeneration (LR). Piezo1, a critical mechanosensory ionchannel, can detect and convert mechanical forces into chemical signals, importing externalstimuli into cells and triggering downstream biological effects. However, the precise role ofPiezo1 in VECs, especially in terms of mediating LR, remains unclear. Here, we report on a potential mechanism by which early changes in hepatic portal hemodynamics activate Piezo1 inVECs to promote hepatocyte proliferation during the process of LR induced by portal vein ligation in rats. In this LR model, hepatocyte proliferation is mainly distributed in zone 1 andzone 2 of liver lobules at 24e48 h after surgery, while only a small number of Ki67-positive hepatocytes were observed in zone 3. Activation of Piezo1 promotes increased secretion of epiregulin and amphiregulin from VECs via the PKC/ERK1/2 axis, further activating epidermalgrowth factor receptor (EGFR) and ERK1/2 signals in hepatocytes and promoting proliferation.In the liver lobules, the expression of EGFR in hepatocytes of zone 1 and zone 2 is significantlyhigher than that in zone 3. The EGFR inhibitor gefitinib inhibits LR by suppressing the proliferation of hepatocytes in the middle zone. These data provide a theoretical basis for the regulation of LR through chemical signals mediated by mechanical stimulation.展开更多
The creation of ex vivo human liver models has long been a critical objective in academic,clinical,and phar-maceutical research,particularly for drug development,where accurate evaluation of hepatic metabolic dy-namic...The creation of ex vivo human liver models has long been a critical objective in academic,clinical,and phar-maceutical research,particularly for drug development,where accurate evaluation of hepatic metabolic dy-namics is crucial.We have developed a bioengineered,perfused,organ-level human liver model that accurately replicates key liver functions,including metabolic activities,and protein synthesis,thus addressing some of the limitations associated with traditional liver monolayers,organoids,and matrix-embedded liver cells.Our approach utilizes liver-specific biomatrix scaffolds,prepared using an innovative protocol and fortified with matrix components that facilitate cellular interactions.These scaffolds,when seeded with human fetal liver cells or co-seeded with liver parenchymal and endothelial cell lines,enable the formation of three-dimensional(3D)human livers with enhanced cellular organization.The“recellularized tissue-engineered livers”(RCLs)have undergone various analyses,demonstrating the capability for establishing liver microenvironments ex vivo.Within 7-14 days,the RCLs exhibit evidence of liver differentiation and metabolic capabilities,underscoring the potential for use in drug metabolism and toxicity studies.Although our study represents a significant step for-ward,we acknowledge the need for direct comparisons with existing models and further research to fully elucidate the spectrum of regenerative responses.The high drug-metabolizing enzyme activity of RCLs,as demonstrated in our study,provides a promising avenue for investigating drug-induced liver injury mechanisms,contributing to a more detailed understanding of early drug discovery processes.展开更多
Sweden has witnessed an increase in the rates of sexual crimes including rape.Knowledge of who the offenders of these crimes are is therefore of importance for prevention.We aimed to study characteristics of individua...Sweden has witnessed an increase in the rates of sexual crimes including rape.Knowledge of who the offenders of these crimes are is therefore of importance for prevention.We aimed to study characteristics of individuals convicted of rape,aggravated rape,attempted rape or attempted aggravated rape(abbreviated rape+),against a woman≥18years of age,in Sweden.By using information from the Swedish Crime Register,offenders between 15 and 60years old convicted of rapeþbetween 2000 and 2015 were included.Information on substance use disorders,previous criminality and psychiatric disorders were retrieved from Swedish population-based registers,and Latent Class Analysis(LCA)was used to identify classes of rapeþoffenders.A total of 3039 offenders were included in the analysis.A major-ity of them were immigrants(n=1800;59.2%)of which a majority(n=1451;47.7%)were born outside of Sweden.The LCA identified two classes:Class A-low offending class(LOC),and Class B—high offending class(HOC).While offenders in the LOC had low rates of previous criminality,psychiatric disorders and substance use disorders,those included in the HOC had high rates of previous criminality,psychiatric disorders and substance use dis-orders.While HOC may be composed by more“traditional”criminals probably known by the police,the LOC may represent individuals not previously known by the police.These two separated classes,as well as our finding in regard to a majority of the offenders being immi-grants,warrants further studies that take into account the contextual characteristics among these offenders.展开更多
Symptomatic neuromas are an all-too-common complication following limb amputation or extremity trauma,leading to chronic and debilitating pain for patients.Surgical resection of symptomatic neuromas has proven to be t...Symptomatic neuromas are an all-too-common complication following limb amputation or extremity trauma,leading to chronic and debilitating pain for patients.Surgical resection of symptomatic neuromas has proven to be the superior method of intervention,but traditional methods of neuroma resection do not address the underlying pathophysiology leading to the formation of a future symptomatic neuroma and lead to high reoperation rates.Novel approaches employ the physiology of peripheral nerve injury to harness the regeneration of nerves to their advantage.This review explores the underlying pathophysiology of neuroma formation and centralization of pain signaling.It compares the traditional surgical approach for symptomatic neuroma resection and describes three novel surgical strategies that harness this pathophysiology of neuroma formation to their advantage.The traditional resection of symptomatic neuromas is currently the standard of care for amputation patients,but new techniques including the regenerative peripheral nerve interface,targeted muscle reinnervation,and intraosseous transposition have shown promise in improving patient pain outcomes for postamputation pain and residual limb pain.Symptomatic neuromas are a chronic and debilitating complication following amputation procedures and trauma,and the current standard of care does not address the underlying pathophysiology leading to the formation of the neuroma.New techniques are under development that may provide improved patient pain outcomes and a higher level of care for symptomatic neuroma resection.展开更多
基金funded by the National Key Research and Development Program of China(No.2021YFF1200901)the National Natural Science Foundation of China(Nos.61721003,62133006,and 92268104)。
文摘The liver performs several vital functions such as metabolism,toxin removal,and glucose storage through the coordination of various cell types.With the recent breakthrough of the single-cell/single-nucleus RNAseq(sc/snRNA-seq)techniques,there is a great opportunity to establish a reference cell map of the liver at single-cell resolution with transcriptome-wise features.In this study,we build a unified liver cell atlas uniLIVER(http://lifeome.net/database/uniliver)by integrative analysis of a large-scale sc/snRNA-seq data collection of normal human liver with 331,125 cells and 79 samples from 6 datasets.Moreover,we introduce LiverCT,a machine learning based method for mapping any query dataset to the liver reference map by introducing the definition of“variant”cellular states analogous to the sequence variants in genomic analysis.Applying LiverCT on liver cancer datasets,we find that the“deviated”states of T cells are highly correlated with the stress pathway activities in hepatocellular carcinoma,and the enrichments of tumor cells with the hepatocyte-cholangiocyte“intermediate”states significantly indicate poor prognosis.Besides,we find that the tumor cells of different patients have different zonation tendencies and this zonation tendency is also significantly associated with the prognosis.This reference atlas mapping framework can also be extended to any other tissues.
基金supported in part by grants from the following sources:the National Natural Science Foundation of China(No.82090051,32371477,92168207)the National Key Research and Development Program of China(No.2022YFA1103400,2022YFC2406704)+1 种基金the Chief Scientist Research Project of Hubei Shizhen Laboratory(HSL2024SX0001)the Beijing Tsinghua Changgung Hospital Foundation(No.12025C01011).
文摘Hepatocellular carcinoma(HCC)is a leading cause of cancer-related mortality,and resistance to systemic therapies remains a significant clinical challenge.This study investigated the mechanisms by which metabolic reprogramming contributes to systemic treatment resistance in HCC.We established HCC cell lines with multidrug resistance characteristics and observed enhanced metabolic activity in these cells.Integrated multiomics analyses revealed hyperactive glucose‒lipid and glutathione metabolic pathways that play critical roles in supporting tumor cell proliferation and survival.We constructed a metabolic reprogramming atlas for HCC-resistant cells and identified aldo-keto reductase(Aldo-keto reductase family 1 Member B1,AKR1B1)as a key regulator of this reprogramming,which sustains drug resistance by regulating energy metabolism and enhancing stress tolerance.Importantly,AKR1B1 expression levels are closely associated with drug resistance and poor prognosis in HCC patients.The secretory nature of AKR1B1 not only underscores its predictive value but also facilitates the intercellular transmission of drug resistance.In terms of overcoming resistance,the AKR1B1 inhibitor epalrestat significantly mitigated drug resistance when it was used in combination with standard therapies.These findings underscore the importance of metabolic reprogramming in the development of HCC resistance.AKR1B1,a key enzyme that regulates metabolic reprogramming,has been identified as a potential biomarker and therapeutic target,providing new insights into overcoming resistance in HCC treatment.
基金supported in part by the National Institutes of Health(NIH)(Grant No.:RF1AG052324)a predoctoral traineeship supported by the NIH T32 training grant on Biology of Aging and Age-related Diseases(Grant No.:T32AG000213)+1 种基金funding provided by the Wisconsin Alumni Research FoundationSchool of Pharmacy,University of Wisconsin-Madison
文摘Diagnosing Alzheimer’s disease(AD)in the early stage is challenging.Informative biomarkers can be of great value for population-based screening.Metabolomics studies have been used to find potential biomarkers,but commonly used tissue sources can be difficult to obtain.The objective of this study was to determine the potential utility of erythrocyte metabolite profiles in screening for AD.Unlike some commonly-used sources such as cerebrospinal fluid and brain tissue,erythrocytes are plentiful and easily accessed.Moreover,erythrocytes are metabolically active,a feature that distinguishes this sample source from other bodily fluids like plasma and urine.In this preliminary pilot study,the erythrocyte metabolomes of 10 histopathologically confirmed AD patients and 10 patients without AD(control(CTRL))were compared.Whole blood was collected post-mortem and erythrocytes were analyzed using ultraperformance liquid chromatography tandem mass spectrometry.Over 750 metabolites were identified in AD and CTRL erythrocytes.Seven were increased in AD while 24 were decreased(P<0.05).The majority of the metabolites increased in AD were associated with amino acid metabolism and all of the decreased metabolites were associated with lipid metabolism.Prominent among the potential biomarkers were 10 sphingolipid or sphingolipid-related species that were consistently decreased in AD patients.Sphingolipids have been previously implicated in AD and other neurological conditions.Furthermore,previous studies have shown that erythrocyte sphingolipid concentrations vary widely in normal,healthy adults.Together,these observations suggest that certain erythrocyte lipid phenotypes could be markers of risk for development of AD.
文摘Purpose: To quantitate the normal level of the tear meniscus, and to determine whether it is an accurate diagnostic indicator of nasolacrimal drainage obstruction. Methods: We performed a retrospective, controlled, case series study on patients evaluated from 2000 to 2002 for epiphora. The height of the tear meniscus was measured using the slit lamp by one experienced observer. Nasolacrimal outflow status was assessed by probing and irrigation. Patency on the nontearing eye was also confirmed by probing and irrigation, and the corresponding tear meniscus levels comprised one control group (59 sides of 62 patients). Tear meniscus levels in patients with ptosis or dermatochalasis without epiphora comprised the second control group (78 sides of 39 patients). The 2 control groups were combined to determine the normal tear meniscus level and ratio between the two sides. The control tear meniscus levels and ratios in patients without epiphora were compared with the tear meniscus levels and ratios in patients with nasolacrimal obstruction (65 sides of 62 patients). Results: The 2 control groups examined did not statistically differ with respect to tear meniscus height (P=0.06). The control median tear meniscus level (0.2mm) significantly differed from the obstructed median tear meniscus level (0.6 mm) (P< 0.0001). The control median ratio between the two sides (1.0) significantly differed from the obstructed ratio (2.5) (P< 0.0001). The absolute tear meniscus level and the tear meniscus ratio were both accurate indicators of obstruction. The percent change in absolute tear meniscus level after lacrimal surgery was- 58.3% . Conclusions: To our knowledge, a quantitative analysis of the tear meniscus height has not been previously documented in the literature. Patients with nasolacrimal system stenosis or obstruction have elevated tear meniscus levels and ratios relative to control subjects. The absolute tear meniscus level and ratio tests are excellent diagnostic indicators of nasolacrimal obstruction and its resolution after successful lacrimal surgery.
文摘Objective: To investigate the law of age-related changes of insulin-like growth factor-1 (IGF-1) expression of rat thyroid cells cultured in vitro. Methods: Rat thyroid of different age (10, 45, 65, 100, 150 weeks) was isolated and thyrocytes cultured. Total RNA was extracted in different rat age group when thyroid cells had been cultured for two weeks. mRNA IGF-1 expression was measured with reverse-transcription polymerase chain reaction( RT-PCR) in each group and compared. Results: Quantity of total RNA in thyroid cells decreased with ageing when the rat thyroid cells had been cultured for 2 weeks. There is significant difference among groups (P<0.05). Expression of IGF-1 mRNA could be detected in thyroid cells of different age cultured in vitro. Quantity of IGF-1 mRNA expression by RT-PCR analysis increased from 10 to 45 weeks old, and then decreased with ageing. Conclusion: Rat thyroid cells from different age cultured in vitro can express IGF-1 mRNA. Quantity of total RNA in thyroid cells cultured in vitro decreased with aging. IGF-1 mRNA expression was correlated to age (r=0.401, P<0.05).
基金a health search grant HR11-043 from the Oklahoma Center for the Advancement of Science and Technology(OCAST)and in part by the Kerr Foundationthe Graduate Program on Interdisciplinary Sciences,Oklahoma State University,Stillwater,OK 74078,USA.Currently,Ms.Nigar Sultana is with P3 Group,Southfield,MI 48034,USA.
文摘This study assessed whether there was a scat tering spectral mar ker quantifiable by reflectance measurements that could indicate early development of hepatic steatosis in rats for potential applications to pre procurement organ evaluation.Sixteen rats were fed a methionine choline-deficient(MCD)diet and eight rats were fed a normal diet.Direct assessment of the liver parenchyma of rats in vivo was performed by percut aneous reflect ance spectroscopy using a single fiber probe at the beginning of diet-intake and arbitrary post-diet-intake times up to 11 weeks to render longitudinal comparison.Histological sampling of the liver over the duration of diet adm inistration was performed on two MCD diet treated rats and one control rat eutha-nized after reflectance spectroscopy measurement.The images of hematoxylin/eosin-stained liver specimens were analyzed morphometrically to evahuate the lipid size changes associated with the level of steatosis.The MCD-diet-treated group(n=16)had mild steatosis in seven rats,moderate in three rats,severe in six rats,and no other significant pathology.No control rats(n=8)developed hepatic steatosis.Among the parameters retrieved from per-SfS,only the scat tering power(can be either positive or negative)appeared to be statist ically diferent between MCD-treated and control livers.The scattering power for the 16 MCD-diet-treated livers at the time of euthanasia and presenting various levels of steatosis was 033±0.21,in comparison to 0.036±0.25 of the eight control livers(p=0.0189).When evaluated at days 12 and 13 combined,the scattering power of the 16 MCD-diet-treated livers was 032±0.17,in comparison to 0.10±0.11 of the eight control livers(p=0.0017).All of four MCD-treated livers harvested at days 12 and 13 presented mild steatosis with sub-micron size lipid droplets,even though none of the MCD-treated livers were sonogr aphically remarkable for fatty changes.The elevation of the scattering power may be a valuable marker indicating early hepatic steatosis before the steatosis is sonographically detectable.
文摘Objectives: To examine the histopathologic features of iridectomy specimens from patients undergoing glaucoma surgery and to compare histologic abnormalities in a group of patients with a history of latanoprost therapy with those in a group of patients who had no history of prostaglandin therapy (controls). Methods: Iridectomy specimens and patient history forms were submitted to the central Latanoprost Pathology Center. These were independently examined by 3 ophthalmic pathologists in a masked fashion. Specimens were evaluated for malignant, premalignant, and other changes including differences in levels of pigmentation, degrees of cellularity, inflammation, vascular abnormalities, and changes in the iris pigment epithelium. Results: Specimens were received from 449 patients with a history of latanoprost treatment and 142 patients who had no history of treatment with latanoprost or other prostaglandin analogues. No evidence of malignant or premalignant changes was found. In latanoprost- treated irides, the prevalence of iris freckles was higher (P=.001) than in control irides, as was the combined number of stromal fibroblasts and melanocytes (P < .001). In a subgroup of specimens received through June 2002, there was no significant difference in mean melanocyte counts (P=.35)- obtained by immunohistochemical staining techniques between the latanoprost- treated and control groups. Conclusions: These findings support previous studies indicating that latanoprost- in- duced eye color changes are due to an increased amount of melanin within the iris stromal melanocytes. The increased numbers of freckles may be a focal manifestation of this effect.
文摘Objective: To review health-related quality of life (QOL) and associated issues and to describe a study investigating “ Child Health Questionnaire” (CHQ) scores in relationship to newborn screening (NBS) for cystic fibrosis (CF) and markers of disease severity. Methods: A total of 36 patients from 10-15.5 years old who were enrolled in the screened or control group of the Wisconsin CF Neonatal Screening Project completed the CHQ. Scale scores comprised the dependent variables. Independent variables included study group and measures of disease severity. Analyses included Fisher’ s exact, 2-sample Wilcoxon, and t tests. Results: QOL did not differ significantly between the screened and control groups for any of the scales. None of the comparisons of CHQ scale scores across measures of disease severity were significant in this small sample, but the CHQ and power were limiting. Conclusions: Our results did not demonstrate a benefit of CF NBS on QOL; however, the CHQ may not be adequately sensitive to QOL in children with CF with disease severity comparable to our sample. The Cystic Fibrosis Questionnaire, a recently validated CF-specific QOL measure for pediatric samples, is likely to provide a more informative evaluation of the effects of CF NBS on patients’ QOL.
基金supported in part by grants from the following sources:National Key Research and Development Program of China(Grant Nos.2022YFA1103400,2022YFC2406704)National Natural Science Foundation of China(Grant Nos.92168207,82090051,32371477)Tsinghua Precision Medicine Foundation(Grant No.2022TS013).
文摘Medical imaging is essential for the diagnosis and treatment of liver diseases,and the objective analysis of such images is vital for precision medicine.Integration of artificial intelligence(AI),particularly computer vision,into hepatology has seen considerable growth.This study conducts a bibliometric analysis to map the evolution,principal trends,and focal points of AI in liver disease imaging research.We conducted a comprehensive literature review using the Web of Science Core Collection and PubMed databases,spanning January 1990 to July 2023,with keywords related to liver diseases and AI in medical imaging.The search resulted in 3,629 documents,with a surge in publications after 2017.The United States and China led in terms of publication volume,with the former exhibiting higher H-index scores and citation counts.However,greater number of research institutions that contribute significantly to publications in the relevant fields are based in China.Keyword analysis revealed extensive research on liver fibrosis,hepatocellular carcinoma,cirrhosis,and fatty liver disease.Techniques such as image segmentation,classification,and registration are prevalent,meeting clinical needs like lesion detection and disease prognosis.Convolutional neural networks(CNNs),particularly U-Net models,are predominantly utilized.This review synthesizes the findings to guide future advancements in AI-assisted liver disease diagnosis and management.
基金supported by the National Key Research and Development Program of China(No.2022YFA1103400)the CAMS Innovation Fund for Medical Sciences(No.2019-I2M-5e056)+2 种基金the National Natural Science Foundation of China(No.81930119,92168207,32371477,82090051)the Precision Medicine Research Program of Tsinghua University(No.10001020612)the National High Level Hospital Clinical Research Funding(China)(No.2022-NHLHCRF-LX-03-0102).
文摘Hepatocyte proliferation is essential for recovering liver function after injury. Inliver surgery, the mechanical stimulation induced by hemodynamic changes triggers vascularendothelial cells (VECs) to secrete large amounts of cytokines that enhance hepatocyte proliferation and play a pivotal role in liver regeneration (LR). Piezo1, a critical mechanosensory ionchannel, can detect and convert mechanical forces into chemical signals, importing externalstimuli into cells and triggering downstream biological effects. However, the precise role ofPiezo1 in VECs, especially in terms of mediating LR, remains unclear. Here, we report on a potential mechanism by which early changes in hepatic portal hemodynamics activate Piezo1 inVECs to promote hepatocyte proliferation during the process of LR induced by portal vein ligation in rats. In this LR model, hepatocyte proliferation is mainly distributed in zone 1 andzone 2 of liver lobules at 24e48 h after surgery, while only a small number of Ki67-positive hepatocytes were observed in zone 3. Activation of Piezo1 promotes increased secretion of epiregulin and amphiregulin from VECs via the PKC/ERK1/2 axis, further activating epidermalgrowth factor receptor (EGFR) and ERK1/2 signals in hepatocytes and promoting proliferation.In the liver lobules, the expression of EGFR in hepatocytes of zone 1 and zone 2 is significantlyhigher than that in zone 3. The EGFR inhibitor gefitinib inhibits LR by suppressing the proliferation of hepatocytes in the middle zone. These data provide a theoretical basis for the regulation of LR through chemical signals mediated by mechanical stimulation.
基金Financial support Studies were funded in part by grants to Yunfang Wang,including National Key Research and Development Program of China(No.2022YFA1103400)National Natural Science Foundation of China(No.92168207)+1 种基金in part to Lola Reid at UNC.Those to Lola Reid included funds from Vesta Therapeutics(Bethesda,MD)that has merged now with PhoenixSongs Biologicals to form Vesta Biotherapeutics(Branford,CT).Praveen Sethupathy,PhD,was funded by an NIDDK/NIH grant(R00DK091318-02)supported in part by Dr.Sethupathy’s R00 grant and as well by a F31 fellowship.
文摘The creation of ex vivo human liver models has long been a critical objective in academic,clinical,and phar-maceutical research,particularly for drug development,where accurate evaluation of hepatic metabolic dy-namics is crucial.We have developed a bioengineered,perfused,organ-level human liver model that accurately replicates key liver functions,including metabolic activities,and protein synthesis,thus addressing some of the limitations associated with traditional liver monolayers,organoids,and matrix-embedded liver cells.Our approach utilizes liver-specific biomatrix scaffolds,prepared using an innovative protocol and fortified with matrix components that facilitate cellular interactions.These scaffolds,when seeded with human fetal liver cells or co-seeded with liver parenchymal and endothelial cell lines,enable the formation of three-dimensional(3D)human livers with enhanced cellular organization.The“recellularized tissue-engineered livers”(RCLs)have undergone various analyses,demonstrating the capability for establishing liver microenvironments ex vivo.Within 7-14 days,the RCLs exhibit evidence of liver differentiation and metabolic capabilities,underscoring the potential for use in drug metabolism and toxicity studies.Although our study represents a significant step for-ward,we acknowledge the need for direct comparisons with existing models and further research to fully elucidate the spectrum of regenerative responses.The high drug-metabolizing enzyme activity of RCLs,as demonstrated in our study,provides a promising avenue for investigating drug-induced liver injury mechanisms,contributing to a more detailed understanding of early drug discovery processes.
基金funding from the European Research Council(ERC)under the European Union’s Horizon 2020 research and innovation programme[grant number 787592].
文摘Sweden has witnessed an increase in the rates of sexual crimes including rape.Knowledge of who the offenders of these crimes are is therefore of importance for prevention.We aimed to study characteristics of individuals convicted of rape,aggravated rape,attempted rape or attempted aggravated rape(abbreviated rape+),against a woman≥18years of age,in Sweden.By using information from the Swedish Crime Register,offenders between 15 and 60years old convicted of rapeþbetween 2000 and 2015 were included.Information on substance use disorders,previous criminality and psychiatric disorders were retrieved from Swedish population-based registers,and Latent Class Analysis(LCA)was used to identify classes of rapeþoffenders.A total of 3039 offenders were included in the analysis.A major-ity of them were immigrants(n=1800;59.2%)of which a majority(n=1451;47.7%)were born outside of Sweden.The LCA identified two classes:Class A-low offending class(LOC),and Class B—high offending class(HOC).While offenders in the LOC had low rates of previous criminality,psychiatric disorders and substance use disorders,those included in the HOC had high rates of previous criminality,psychiatric disorders and substance use dis-orders.While HOC may be composed by more“traditional”criminals probably known by the police,the LOC may represent individuals not previously known by the police.These two separated classes,as well as our finding in regard to a majority of the offenders being immi-grants,warrants further studies that take into account the contextual characteristics among these offenders.
文摘Symptomatic neuromas are an all-too-common complication following limb amputation or extremity trauma,leading to chronic and debilitating pain for patients.Surgical resection of symptomatic neuromas has proven to be the superior method of intervention,but traditional methods of neuroma resection do not address the underlying pathophysiology leading to the formation of a future symptomatic neuroma and lead to high reoperation rates.Novel approaches employ the physiology of peripheral nerve injury to harness the regeneration of nerves to their advantage.This review explores the underlying pathophysiology of neuroma formation and centralization of pain signaling.It compares the traditional surgical approach for symptomatic neuroma resection and describes three novel surgical strategies that harness this pathophysiology of neuroma formation to their advantage.The traditional resection of symptomatic neuromas is currently the standard of care for amputation patients,but new techniques including the regenerative peripheral nerve interface,targeted muscle reinnervation,and intraosseous transposition have shown promise in improving patient pain outcomes for postamputation pain and residual limb pain.Symptomatic neuromas are a chronic and debilitating complication following amputation procedures and trauma,and the current standard of care does not address the underlying pathophysiology leading to the formation of the neuroma.New techniques are under development that may provide improved patient pain outcomes and a higher level of care for symptomatic neuroma resection.
