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Biomedical subjects

Nan Lin

Publications and source records attributed to Nan Lin.

At least 19 recordsLinked to original sources

Genomic analyses implicate hormonal and metabolic dysregulation in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) and its underlying features remain poorly understood. In this genetic study (n = 544,513), we expand the number of genetic loci from 16 to 29, and additionally identify 31 associated plasma proteins. Many risk-increasing loci were associated with later age at menopause, underscoring the reproductive longevity related to an increased oocyte number and/or availability across the lifespan. Hormonal regulation in the etiology of this condition, through metabolic and reproductive features, was emphasized. The proteomic analysis highlighted metabolic biology known to be related to PCOS. A polygenic risk score (PRS) was associated with adverse cardiometabolic outcomes, with differing relevance of testosterone and body mass index in women and men. Finally, while oligo-anovulation and anovulatory infertility are features of PCOS, we observed no impact of PCOS susceptibility on childlessness. We suggest that PCOS susceptibility confers balanced pleiotropic influences on fertility in women, and life-long adverse metabolic consequences in both sexes.

Humans↗

Genomic Insights Into Local Adaptation Across Heterogeneous Understory Habitats and Climate Change Vulnerability.

Understanding adaptive evolution and survival risks in understory herbs is crucial for the effective conservation of biodiversity. How environmental gradients shape species local adaptation patterns is not well understood, nor is how populations of understory herbs respond to a changing climate. In this study, we conducted population genomic analyses of Adenocaulon himalaicum (Asteraceae) with a pan-East Asian distribution, representing a good model for dominant understory herbs to elucidate adaptation mechanisms in heterogeneous forest ecosystems. Based on 34,398 putatively neutral single nucleotide polymorphisms (SNPs) across 27 populations, we identified three genetic lineages accompanied by high levels of genetic differentiation between populations. Our isolation by environment results (IBE) indicated a significant effect of environmental gradients on genomic variation of A. himalaicum (r = 0.18, p = 0.03). To decompose the relative contributions of climate, geography and population structure in explaining genetic variance, our partial RDA found that the prominent contribution of environmental effects (climatic and soil variables) explained 29% and 36% of the neutral and adaptive genetic variation, respectively. Using two genotype-environment association (GEA) methods, we identified 13 SNPs as candidates for core climate-related adaptation loci, with two of these loci further validated by qRT-PCR experiments. Projections of spatiotemporal genomic vulnerability under different future climate scenarios revealed that populations in the southeastern edge of the Himalayas, near the Sichuan Basin, the southernmost region of Northeast China and the northern Korean Peninsula, as well as northern Japan, were identified as the most vulnerable and should be prioritised for conservation. Therefore, our current study provides the genomic foundations for conservation and management strategies to elucidate how these understory herbs cope with future climate changes.

Climate Change↗

Genome sequencing and population genomics provide insights into the demographic history, genetic load, and local adaptation of an endangered Tertiary relict.

Endangered Tertiary relict trees represent an exceptional evolutionary heritage with small and isolated populations, yet little is known about how demographic history, local adaptation, and genetic load have affected their long-term survival and extinction risk. We performed whole-genome sequencing and population genomic analyses on Ulmus elongata L. K. Fu & C. S. Ding, an endangered Tertiary relict tree endemic to East Asia. By integrating genomes from U. elongata and seven other endangered trees from public databases, we identified rate-decelerated genes across endangered trees and genes under positive selection of U. elongata associated with tissue development, detoxification, and immune response, and signal transduction and regulation mechanisms potentially leading to endangered status. Demographic analyses revealed continuous population decline from the late Miocene to present, especially during the last glacial maximum (LGM) and last 10&#x2009;000&#x2009;years. Spearman correlation indicated a strong negative relationship between effective population size and human population density (rpopulation density&#x2009;=&#x2009;-0.90, P&#x2009;<&#x2009;0.001) as well as cropland use (rcropland use&#x2009;=&#x2009;-0.89, P&#x2009;<&#x2009;0.001). Genotype-environment association (GEA) analyses identified a set of candidate genes associated with temperature and precipitation, supporting a polygenic adaptation model in U. elongata. Overall, our findings underscore the severe population bottlenecks that have led to the fixation of strongly deleterious mutations and inbreeding, further compromising the adaptive potential and long-term viability of U. elongata. Furthermore, assessments of genomic vulnerability under future climate scenarios revealed higher genetic offsets in northern region of Fujian and Jiangxi populations, suggesting these regions require prioritized conservation efforts due to reduced adaptive capacity.

Endangered Species↗

Multiomics analyses provide insights into the genomic basis of differentiation among four sweet osmanthus groups.

Sweet osmanthus (Osmanthus fragrans) is famous in China for its flowers and contains four groups: Albus, Luteus, Aurantiacus, and Asiaticus. Understanding the relationships among these groups and the genetic mechanisms of flower color and aroma biosynthesis are of tremendous interest. In this study, we sequenced representative varieties from two of the four sweet osmanthus groups. Multiomics and phylogenetic analyses of varieties from each of the four groups showed that Asiaticus split first within the species, followed by Aurantiacus and the sister groups Albus and Luteus. We show that the difference in flower color between Aurantiacus and the other three groups was caused by a 4-bp deletion in the promoter region of carotenoid cleavage dioxygenase 4 (OfCCD4) that leads to expression decrease. In addition, we identified 44 gene pairs exhibiting significant structural differences between the multiseasonal flowering variety "Rixianggui" in the Asiaticus group and other autumn-flowering varieties. Through correlation analysis between intermediate products of aromatic components and gene expression, we identified eight genes associated with the linalool and &#x3b1;- and &#x3b2;-ionone biosynthesis pathways. Overall, our study offers valuable genetic resources for sweet osmanthus, while also providing genetic clues for improving the flower color and multiseasonal flowering of osmanthus and other flowers.

Oleaceae↗

Morphological heterogeneity of CA1 pyramidal neurons in response to ischemia.

We have found, based on the electrophysiological properties, two subtypes of CA1 pyramidal neurons in the CA1 region of the normal hippocampus, late postsynaptic potential (L-PSP) neurons and non-L-PSP neurons. In addition, our previous study has shown that the electrophysiological properties of these two subtypes of pyramidal neurons were differentially modified after ischemia. In the present study, we hypothesized that ischemia might also induce different morphological alterations in these two subtypes of neuron. To test the hypothesis, we compared the changes in the dendritic arborization and soma volume of these two subtypes of neurons in rats subjected to transient global ischemia. We found a significant decrease in the basal dendritic length of L-PSP neurons at 12 hr after reperfusion, resulting mainly from a significant decrease in the dendrite terminal length. The apical dendritic length of L-PSP neurons markedly increased at 24 hr after ischemia, resulting mainly from an increase in the number of branching arbors in the middle part of the apical dendritic trees. The soma size of L-PSP neurons was significantly reduced at 12 hr, but they became slightly larger at 24 hr and 48 hr after reperfusion. In contrast to L-PSP neurons, non-L-PSP neurons showed slight modifications in the dendritic arborization but had persistent swelling of their soma after ischemia. These results indicate that pathological changes in these two subtypes of neurons are different after ischemia.

Animals↗

Splenectomy with endoscopic variceal ligation is superior to splenectomy with pericardial devascularization in treatment of portal hypertension.

AIM: To investigate the therapeutic efficacy and complications of splenectomy with endoscopic variceal ligation (EVL) and splenectomy with pericardial devascularization (i.e. Hassab's operation) in patients with portal hypertension. METHODS: A total of 103 patients with liver cirrhosis and portal hypertension were randomly selected to receive either splenectomy with EVL (n = 53, group A) or Hassab's operation (n = 50, group B). RESULTS: The portal blood flow volume, the presence of portal vein thrombosis, gastric emptying time and free portal venous pressure (FPP) before and after the operation were determined. Patients were followed up for up to 64 mo with an average of 45 mo, and the Dagradi classification of variceal veins and the grading of portal hypertension gastropathy (PHG) were evaluated. It was found that all esophageal varices were occluded or decreased to grade II or less in both groups. There was little difference in the recurrence rate of esophageal varices (11.9% vs 13.2%) and the re-bleeding rate (7.1% vs 5.3%) between groups A and B. The incidence of complications and the percentage of patients with severe PHG after the operation were significantly higher in group B (60.0% and 52.0%) than in group A (32.1% and 20.8%, P < 0.05). No patients died of operation-related complications. There was no significant difference in gastric emptying time, FPP and portal blood flow volume between the two groups. CONCLUSION: The results suggest that splenectomy with EVL achieves similar therapeutic efficacy to that of Hassab's operation in terms of the recurrence rate of esophageal varices and the re-bleeding rate, but the former results in fewer and milder complications.

Female↗

Evaluation of the effects of combined endoscopic variceal ligation and splenectomy with pericardial devascularization on esophageal varices.

AIM: To detect the hemodynamic alterations in collateral circulation before and after combined endoscopic variceal ligation (EVL) and splenectomy with pericardial devascularization by ultrasonography, and to evaluate their effect using hemodynamic parameters. METHODS: Forty-three patients with esophageal varices received combined EVL and splenectomy with pericardial devascularization for variceal eradication. The esophageal vein structures and azygos blood flow (AZBF) were detected by endoscopic ultrasonography and color Doppler ultrasound. The recurrence and rebleeding of esophageal varices were followed up. RESULTS: Patients with moderate or severe varices in the esophageal wall and those with severe peri-esophageal collateral vein varices had improvements after treatment, while the percentage of patients with severe para-esophageal collateral vein varices decreased from 54.49% to 2.33%, and the percentage of patients with detectable perforating veins decreased from 79.07% to 4.65% (P < 0.01). Color Doppler flowmetry showed a significant decrease both in AZBF (43.00%, P < 0.05) and in diameter of the azygos vein (28.85%, P < 0.05), while the blood flow rate was unchanged. The recurrence rate of esophageal varices was 2.5% (1/40, mild), while no re-bleeding cases were recorded. CONCLUSION: EVL in combination with splenectomy with pericardial devascularization can block the collateral veins both inside and outside of the esophageal wall, and is more advantagious over splenectomy in combination with pericardial devascularization or EVL in preventing recurrence and re-bleeding of varices.

Adult↗

[Effects of different treatment complex on esophageal vascular structures in patients with portal hypertension].

OBJECTIVE: To assess the effects of different treatment complex on esophageal vascular structures in patients with portal hypertension. METHODS: Patients (142 cases) with esophageal varices received either endoscopic variceal ligation (EVL) alone (54 cases), pericardial devascularization procedure (PDP) alone (23 cases), a combination of EVL and partial splenic embolization (PSE) (34 cases), or a combination of EVL and PDP (31 cases) for variceal eradication. Esophageal vascular structures were examined with miniature ultrasonic probe. The recurrence and rebleeding of esophageal varices were investigated. RESULTS: Esophageal submucous varices were obliterated and collateral veins remained unchanged in patients treated by EVL or EVL combined with PSE; esophageal submucous varices were diminished in size and collateral veins were obliterated by PDP, and both esophageal submucous varices and collateral veins were obliterated by the combination of EVL and PDP. CONCLUSIONS: The combination of EVL and Hassab's procedure can effectively shut off the portoazygous shunt, prevent esophageal varices from bleeding and recurrence. It's a simply and less cost procedure.

Cardia↗

[Clinical study on crossed disparity and uncrossed disparity in intermittent exotropia before and after surgery].

OBJECTIVE: To understand the clinical variety of zero disparity, crossed disparity and uncrossed disparity in intermittent exotropia before and after strabismus surgery. METHODS: 100 cases of intermittent exotropia were involved in the study. Before and after surgery, zero disparity stereo-acuity, crossed disparity and uncrossed disparity stereo-acuity were examined with stereogram designed by Yan Shaoming, distance fusion range and distance stereo-acuity were examined with traditional and random dot synoptophore stereogram. The patients were divided into four groups based on the results of the stereogram examination before surgery. RESULTS: In the 100 cases, there was no coexistence of zero disparity and uncrossed disparity, no coexistence of crossed and uncrossed disparity, and no existence of only crossed disparity or only uncrossed disparity. Postoperative zero disparity, crossed disparity, uncrossed disparity, distance fusion range and distance stereo-acuity improved significantly compared with the preoperative results for each group (P < 0.01). The comparison of distance fusion range was not prominent before and after strabismus surgery in the 4 groups (P > 0.05). The distribution of distance stereo-acuity was prominent after strabismus surgery in the 4 groups (P < 0.01). Distance stereo-acuity rebuilding after surgery in group 1 and group 2 was better than that in group 3 and group 4. CONCLUSIONS: (1) In the cases with intermittent exotropia, zero disparity stereo-acuity, crossed disparity and uncrossed disparity stereo-acuity are abnormal. The sequential damage of stereopsis is uncrossed disparity, crossed disparity and zero disparity. The sequential rebuilding of stereopsis is zero disparity, crossed disparity and uncrossed disparity. (2) The serious damage or disappearance of uncrossed disparity stereo-acuity is the indication of intermittent exotropia surgery for perfect binocular vision rebuilding.

Adolescent↗

Are scale-free networks robust to measurement errors?

BACKGROUND: Many complex random networks have been found to be scale-free. Existing literature on scale-free networks has rarely considered potential false positive and false negative links in the observed networks, especially in biological networks inferred from high-throughput experiments. Therefore, it is important to study the impact of these measurement errors on the topology of the observed networks. RESULTS: This article addresses the impact of erroneous links on network topological inference and explores possible error mechanisms for scale-free networks with an emphasis on Saccharomyces cerevisiae protein interaction networks. We study this issue by both theoretical derivations and simulations. We show that the ignorance of erroneous links in network analysis may lead to biased estimates of the scale parameter and recommend robust estimators in such scenarios. Possible error mechanisms of yeast protein interaction networks are explored by comparisons between real data and simulated data. CONCLUSION: Our studies show that, in the presence of erroneous links, the connectivity distribution of scale-free networks is still scale-free for the middle range connectivities, but can be greatly distorted for low and high connecitivities. It is more appropriate to use robust estimators such as the least trimmed mean squares estimator to estimate the scale parameter gamma under such circumstances. Moreover, we show by simulation studies that the scale-free property is robust to some error mechanisms but untenable to others. The simulation results also suggest that different error mechanisms may be operating in the yeast protein interaction networks produced from different data sources. In the MIPS gold standard protein interaction data, there appears to be a high rate of false negative links, and the false negative and false positive rates are more or less constant across proteins with different connectivities. However, the error mechanism of yeast two-hybrid data may be very different, where the overall false negative rate is low and the false negative rates tend to be higher for links involving proteins with more interacting partners.

Algorithms↗

[Specialization in thyroid surgery].

OBJECTIVE: To evaluate the results of surgically treated patients with benign thyroid disorders from Department of Otolaryngology- Head and Neck Surgery. METHODS: The clinical data of 496 patients operated for benign thyroid disorders were retrospectively analyzed in this department from January 2001 to April 2004. The incidence of complications, particularly postoperative permanent recurrent laryngeal nerve palsy and hypocalcemia, duration of surgery, incision length on the neck, hospitalization days and postoperative recurrence were evaluated. RESULTS: Unilateral total thyroidectomy with contralateral partial lobectomy was performed in 314 cases, unilateral total thyroidectomy with isthmectomy in 76, bilateral subtotal thyroidectomy with the remnant left at the upper pole in 29, isthmectomy in 3, total thyroidectomy in 46. The operations on 28 patients with substernal goiter have been successfully performed via cervical collar incision. Of these patients, the incidences of unilateral recurrent laryngeal nerve paralysis and temporary postoperative hypocalcemia were 0.2% (1/496) and 1.8% (9/496), respectively. There were no bilateral vocal cord paralyses and permanent hypocalcaemia. Postoperative hemorrhage requiring reoperation occurred in 3 cases (0.6%). No patients had incision infection. The mean duration of surgery was 66 min. The mean incision length on the neck was 5.2 cm. The incidence of postoperative recurrence was 0.2% (1/496). The mean hospitalization day was 6.3 d. CONCLUSIONS: Otolaryngologists who had received stringent training of head and neck surgery seem to have the advantage to avoid injury of recurrent nerve in the thyroid surgery.

Adult↗

Information assessment on predicting protein-protein interactions.

BACKGROUND: Identifying protein-protein interactions is fundamental for understanding the molecular machinery of the cell. Proteome-wide studies of protein-protein interactions are of significant value, but the high-throughput experimental technologies suffer from high rates of both false positive and false negative predictions. In addition to high-throughput experimental data, many diverse types of genomic data can help predict protein-protein interactions, such as mRNA expression, localization, essentiality, and functional annotation. Evaluations of the information contributions from different evidences help to establish more parsimonious models with comparable or better prediction accuracy, and to obtain biological insights of the relationships between protein-protein interactions and other genomic information. RESULTS: Our assessment is based on the genomic features used in a Bayesian network approach to predict protein-protein interactions genome-wide in yeast. In the special case, when one does not have any missing information about any of the features, our analysis shows that there is a larger information contribution from the functional-classification than from expression correlations or essentiality. We also show that in this case alternative models, such as logistic regression and random forest, may be more effective than Bayesian networks for predicting interactions. CONCLUSIONS: In the restricted problem posed by the complete-information subset, we identified that the MIPS and Gene Ontology (GO) functional similarity datasets as the dominating information contributors for predicting the protein-protein interactions under the framework proposed by Jansen et al. Random forests based on the MIPS and GO information alone can give highly accurate classifications. In this particular subset of complete information, adding other genomic data does little for improving predictions. We also found that the data discretizations used in the Bayesian methods decreased classification performance.

Artificial Intelligence↗

Therapeutic effects of endoscopic variceal ligation combined with partial splenic embolization for portal hypertension.

AIM: To evaluate the feasibility of a new strategy of endoscopic variceal ligation combined with partial splenic embolization (EVL-PSE) for patients with cirrhosis and portal hypertension. METHODS: From May 1999 to May 2002, 41 cases with cirrhosis and portal hypertension underwent EVL-PSE. Hemodynamics of the main portal vein (MPV), the left gastric vein (LGV) and azygos vein, including maximum velocity, flow rate and vein diameter, were assessed by Doppler ultrasonography. RESULTS: One case died from pulmonary artery embolism. One case complicated with splenic abscess was successfully managed by laparotomy. The esophageal varices and hypersplenism were well controlled after EVL-PSE in other patients. After EVL-PSE, the flow rate and velocity of MPV was significantly reduced (P<0.05), as well as the flow rate of the LGV and azygos vein. During the follow-up, no recurrent bleeding was found. CONCLUSION: Being more convenient and less invasive, EVL-PSE is hopeful to be a proper intervention strategy for portal hypertensive patients with impaired hepatic function or those intolerant to shunting or devascularization surgery.

Adult↗

Computational and experimental studies on human misshapen/NIK-related kinase MINK-1.

We have studied the structure and function of Human Misshapen/NIK-related kinase (MINK-1) through a combination of computational methods and experimental approaches, including (1) fold recognition and sequence-structure alignment for each structural domain using the threading program PROSPECT, (2) gene expression and protein-protein interaction analysis of yeast homologs of human MINK-1 domains, and (3) yeast two-hybrid screening for proteins that interact with human MINK-1. Our structure prediction dissects MINK-1 into four domains: a conserved N-terminal kinase domain, followed by a coiled-coil region and a proline-rich region, and a C-terminal GCK domain. Gene expression and yeast two-hybrid analysis of yeast homologs of the MINK-1 domains suggest that MINK-1 may be involved in cell-cycle progression and cytoskeletal control. Consistent with these predicted functions, our in-house yeast two-hybrid screen for proteins that interact with human MINK-1 provides strong evidence that the coiled-coil and proline-rich domains of MINK-1 participate in the regulation of cytoskeletal organization, cell-cycle control and apoptosis. A homology model of the MINK-1 kinase domain was used to screen the NCI open compound database in DOCK, and chemical compounds with pharmaceutically acceptable properties were identified. Further medicinal chemistry compound structure optimization and kinase assays are underway.

Amino Acid Sequence↗

[Splenectomy combined with endoscopic variceal ligation in treating portal hypertension].

OBJECTIVE: To investigate the therapeutic effect of endoscopic variceal ligation (EVL) combined with splenectomy on patients with portal hypertension. METHODS: The eliminating rate of varicose veins and recurrent bleeding rate were evaluated. Fifty-one paitents with cirrhosis of liver and portal hypertension were randomly divided into 2 groups. We treated 25 portal hypertensive patients using splenectomoy plus EVL. The therapeutic effect of pericardial devascularization in 26 patients with upper gastrointestinal bleeding due to portal hypertension served as the control. RESULTS: All patients were followed up for 12 months. There was no death due to the operation. All patients in the study group had no upper gastrointestinal rebleeding during the 12-month follow-up. The rebleeding rate in the control group was 11.5% (3/26). The varicose venis eliminating rate was 96% (24/25) in the study group and 50% (13/26) in the control group (P < 0.01). It showed no effect on portal hypertensive gastropathy in the study group, and pericardial devascularization procedure exacerbated the portal hypertensive gastropathy. The thrombosis rate in the portal vein after the operation was 8% (2/25) in the study group and 34.6% (9/26) in the control group (P < 0.05). CONCLUSION: EVL combined with splenectomy has less trauma, fewer postoperative complications and high eradication of esophageal varices. It can be used safely in treating portal hypertension.

Esophageal and Gastric Varices↗

[Treatment of portal hypertension by endoscopic esophageal ligation of varicose veins combined with partial splenic embolization].

OBJECTIVE: To evaluate the feasibility and efficacy of a new method of endoscopic esophageal variceal ligation combined with partial splenic embolization (EVL-PSE) for the patients with portal hypertension. METHODS: From May 1999 to February 2003, sixty-eight patients with portal hypertension underwent EVL-PSE, and hemodynamics of the portal trunk (PT), the left gastric vein and azygos vein, including maximum velocity, flow volume, vein diameter, were assessed using color ultrasound Doppler. RESULTS: The esophageal varices and hypersplenism were greatly ameliorated after operation in patients who had undergone EVL-PSE. Postoperative portal trunk flow volume and velocity were significantly reduced (P < 0.05), and flow volume of the left gastric vein as well as the azygos vein were also reduced after operation. During 2 - 24-month follow-up, no recurrent bleeding was found. CONCLUSIONS: EVL-PSE is less traumatic with less complications, and results in marked eradication of esophageal varices, it can be carried out safely in the clinical treatment for patients with portal hypertension.

Adult↗