Multiple Human Population Movements and Cultural Dispersal Events Shaped the Landscape of Chinese Paternal Heritage.

Large-scale genomic projects and ancient DNA innovations have ushered in a new paradigm for exploring human evolutionary history. However, the genetic legacy of spatiotemporally diverse ancient Eurasians within Chinese paternal lineages remains unresolved. Here, we report an integrated Y-chromosome genomic database encompassing 15,563 individuals from both modern and ancient Eurasians, including 919 newly reported individuals, to investigate the Chinese paternal genomic diversity. The high-resolution, time-stamped phylogeny reveals multiple diversification events and extensive expansions in the early and middle Neolithic. We identify four major ancient population movements, each associated with technological innovations that have shaped the Chinese paternal landscape. First, the expansion of early East Asians and millet farmers from the Yellow River Basin predominantly carrying O2/D subclades significantly influenced the formation of the Sino-Tibetan people and facilitated the permanent settlement of the Tibetan Plateau. Second, the dispersal of rice farmers from the Yangtze River Valley carrying O1 and certain O2 sublineages reshapes the genetic makeup of southern Han Chinese, as well as the Tai-Kadai, Austronesian, Hmong-Mien, and Austroasiatic people. Third, the Neolithic Siberian Q/C paternal lineages originated and proliferated among hunter-gatherers on the Mongolian Plateau and the Amur River Basin, leaving a significant imprint on the gene pools of northern China. Fourth, the J/G/R paternal lineages derived from western Eurasia, which were initially spread by Yamnaya-related steppe pastoralists, maintain their presence primarily in northwestern China. Overall, our research provides comprehensive genetic evidence elucidating the significant impact of interactions with culturally distinct ancient Eurasians on the patterns of paternal diversity in modern Chinese populations.

Differentiated genomic footprints suggest isolation and long-distance migration of Hmong-Mien populations.

BACKGROUND: The underrepresentation of Hmong-Mien (HM) people in Asian genomic studies has hindered our comprehensive understanding of the full landscape of their evolutionary history and complex trait architecture. South China is a multi-ethnic region and indigenously settled by ethnolinguistically diverse HM, Austroasiatic (AA), Tai-Kadai (TK), Austronesian (AN), and Sino-Tibetan (ST) people, which is regarded as East Asia's initial cradle of biodiversity. However, previous fragmented genetic studies have only presented a fraction of the landscape of genetic diversity in this region, especially the lack of haplotype-based genomic resources. The deep characterization of demographic history and natural-selection-relevant genetic architecture of HM people was necessary. RESULTS: We reported one HM-specific genomic resource and comprehensively explored the fine-scale genetic structure and adaptative features inferred from the genome-wide SNP data of 440 HM individuals from 33 ethnolinguistic populations, including previously unreported She. We identified solid genetic differentiation between HM people and Han Chinese at 7.64‒15.86 years ago (kya) and split events between southern Chinese inland (Miao/Yao) and coastal (She) HM people in the middle Bronze Age period and the latter obtained more gene flow from Ancient Northern East Asians. Multiple admixture models further confirmed that extensive gene flow from surrounding ST, TK, and AN people entangled in forming the gene pool of Chinese coastal HM people. Genetic findings of isolated shared unique ancestral components based on the sharing alleles and haplotypes deconstructed that HM people from the Yungui Plateau carried the breadth of previously unknown genomic diversity. We identified a direct and recent genetic connection between Chinese inland and Southeast Asian HM people as they shared the most extended identity-by-descent fragments, supporting the long-distance migration hypothesis. Uniparental phylogenetic topology and network-based phylogenetic relationship reconstruction found ancient uniparental founding lineages in southwestern HM people. Finally, the population-specific biological adaptation study identified the shared and differentiated natural selection signatures among inland and coastal HM people associated with physical features and immune functions. The allele frequency spectrum of cancer susceptibility alleles and pharmacogenomic genes showed significant differences between HM and northern Chinese people. CONCLUSIONS: Our extensive genetic evidence combined with the historical documents supported the view that ancient HM people originated from the Yungui regions associated with ancient "Three-Miao tribes" descended from the ancient Daxi-Qujialing-Shijiahe people. Then, some have recently migrated rapidly to Southeast Asia, and some have migrated eastward and mixed respectively with Southeast Asian indigenes, Liangzhu-related coastal ancient populations, and incoming southward ST people. Generally, complex population migration, admixture, and adaptation history contributed to the complicated patterns of population structure of geographically diverse HM people.

Differentiated adaptative genetic architecture and language-related demographical history in South China inferred from 619 genomes from 56 populations.

BACKGROUND: The underrepresentation of human genomic resources from Southern Chinese populations limited their health equality in the precision medicine era and complete understanding of their genetic formation, admixture, and adaptive features. Besides, linguistical and genetic evidence supported the controversial hypothesis of their origin processes. One hotspot case was from the Chinese Guangxi Pinghua Han people (GPH), whose language was significantly similar to Southern Chinese dialects but whose uniparental gene pool was phylogenetically associated with the indigenous Tai-Kadai (TK) people. Here, we analyzed genome-wide SNP data in 619 people from four language families and 56 geographically different populations, in which 261 people from 21 geographically distinct populations were first reported here. RESULTS: We identified significant population stratification among ethnolinguistically diverse Guangxi populations, suggesting their differentiated genetic origin and admixture processes. GPH shared more alleles related to Zhuang than Southern Han Chinese but received more northern ancestry relative to Zhuang. Admixture models and estimates of genetic distances showed that GPH had a close genetic relationship with geographically close TK compared to Northern Han Chinese, supporting their admixture origin hypothesis. Further admixture time and demographic history reconstruction supported GPH was formed via admixture between Northern Han Chinese and Southern TK people. We identified robust signatures associated with lipid metabolisms, such as fatty acid desaturases (FADS) and medically relevant loci associated with Mendelian disorder (GJB2) and complex diseases. We also explored the shared and unique selection signatures of ethnically different but linguistically related Guangxi lineages and found some shared signals related to immune and malaria resistance. CONCLUSIONS: Our genetic analysis illuminated the language-related fine-scale genetic structure and provided robust genetic evidence to support the admixture hypothesis that can explain the pattern of observed genetic diversity and formation of GPH. This work presented one comprehensive analysis focused on the population history and demographical adaptative process, which provided genetic evidence for personal health management and disease risk prediction models from Guangxi people. Further large-scale whole-genome sequencing projects would provide the entire landscape of southern Chinese genomic diversity and their contributions to human health and disease traits.

NMNATs expression inhibition mediated NAD+ deficiency plays a critical role in doxorubicin-induced hepatotoxicity in mice.

Doxorubicin (DOX) is one of the most widely used antineoplastic drugs with known cardiotoxicity while other organ toxicity, such as hepatotoxicity is not well defined. This study was to explore the role of nicotinamide adenine dinucleotide (NAD+) in DOX-induced hepatotoxicity. DOX (20 mg/kg) induced acute liver injury and oxidative stress in C57BL/6 J mice at 48 h. Notably, the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and NAD(P)H dehydrogenase quinone 1 (NQO1) were downregulated. NAD+ deficiency was confirmed due to DOX exposure. Mechanistically, the downregulation of nicotinamide mononucleotide adenylyl transferase 1 (NMNAT1), NMNAT2 and NMNAT3, while no alteration of nicotinamide phosphoribosyl transferase was proved. As a consequence of NAD+ deficiency, the expression of poly-ADP-ribose polymerase1 (PARP1), CD38 and Sirtuin1 (SIRT1) were reduced. Furthermore, supplementation of NAD+ (200 mg/kg/day) or its precursor nicotinamide mononucleotide (NMN) (500 mg/kg/day) alleviated liver injury, attenuated oxidative stress, and elevated the downregulation of Nrf2 and NQO1. More importantly, compromised expression of NMNAT1-3, PARP1, CD38 and SIRT1 were improved by NAD+ and NMN. In conclusion, NAD+ deficiency due to NMNATs expression inhibition may attribute to the pathogenesis of DOX-induced hepatotoxicity, thus providing new insights for mitigating DOX side effects.

Genome-wide allele and haplotype-sharing patterns suggested one unique Hmong-Mein-related lineage and biological adaptation history in Southwest China.

BACKGROUND: Fine-scale genetic structure of ethnolinguistically diverse Chinese populations can fill the gap in the missing diversity and evolutionary landscape of East Asians, particularly for anthropologically informed Chinese minorities. Hmong-Mien (HM) people were one of the most significant indigenous populations in South China and Southeast Asia, which were suggested to be the descendants of the ancient Yangtze rice farmers based on linguistic and archeological evidence. However, their deep population history and biological adaptative features remained to be fully characterized. OBJECTIVES: To explore the evolutionary and adaptive characteristics of the Miao people, we genotyped genome-wide SNP data in Guizhou HM-speaking populations and merged it with modern and ancient reference populations via a comprehensive population genetic analysis and evolutionary admixture modeling. RESULTS: The overall genetic admixture landscape of Guizhou Miao showed genetic differentiation between them and other linguistically diverse Guizhou populations. Admixture models further confirmed that Miao people derived their primary ancestry from geographically close Guangxi Gaohuahua people. The estimated identity by descent and effective population size confirmed a plausible population bottleneck, contributing to their unique genetic diversity and population structure patterns. We finally identified several natural selection candidate genes associated with several biological pathways. CONCLUSIONS: Guizhou Miao possessed a specific genetic structure and harbored a close genetic relationship with geographically close southern Chinese indigenous populations and Guangxi historical people. Miao people derived their major ancestry from geographically close Guangxi Gaohuahua people and experienced a plausible population bottleneck which contributed to the unique pattern of their genetic diversity and structure. Future ancient DNA from Shijiahe and Qujialing will provide new insights into the origin of the Miao people.

Extensive genetic admixture between Tai-Kadai-speaking people and their neighbours in the northeastern region of the Yungui Plateau inferred from genome-wide variations.

BACKGROUND: Yungui Plateau in Southwest China is characterized by multi-language and multi-ethnic communities and is one of the regions with the wealthiest ethnolinguistic, cultural and genetic diversity in East Asia. There are numerous Tai-Kadai (TK)-speaking populations, but their detailed evolutionary history and biological adaptations are still unclear. RESULTS: Here, we genotyped genome-wide SNP data of 77 unrelated TK-speaking Zhuang and Dong individuals from the Yungui Plateau and explored their detailed admixture history and adaptive features using clustering patterns, allele frequency differentiation and sharing haplotype patterns. TK-speaking Zhuang and Dong people in Guizhou are closely related to geographically close TK and Hmong-Mien (HM)-speaking populations. Besides, we identified that Guizhou TK-speaking people have a close genetic relationship with Austronesian (AN)-speaking Atayal and Paiwan people, which is supported by the common origin of the ancient Baiyue tribe. We additionally found subtle genetic differences among the newly studied TK people and previously reported Dais via the fine-scale genetic substructure analysis based on the shared haplotype chunks. Finally, we identified specific selection candidate signatures associated with several essential human immune systems and neurological disorders, which could provide evolutionary evidence for the allele frequency distribution pattern of genetic risk loci. CONCLUSIONS: Our comprehensive genetic characterization of TK people suggested the strong genetic affinity within TK groups and extensive gene flow with geographically close HM and Han people. We also provided genetic evidence that supported the common origin hypothesis of TK and AN people. The best-fitted admixture models further suggested that ancestral sources from northern millet farmers and southern inland and coastal people contributed to the formation of the gene pool of the Zhuang and Dong people.

A case of unexpected death due to primary angiitis of the central nervous system.

Primary angiitis of the central nervous system (PACNS) is a rare and fatal cerebral vasculitis mainly involving the arteriole of the pia mater, cerebral cortex, and spinal cord. It has an insidious onset atypical symptoms. In this paper, we reported an unexpected death due to cerebral hemorrhage caused by PACNS. According to the typical clinical manifestations (headache, dizziness, weakness of the limbs, temporary blurred vision, etc.) and pathological examination (wide degeneration and fibrinoid necrosis of blood vessel walls with inflammatory cell infiltration), as well as hematoxylin-eosin staining, immunohistochemistry for CD15 + and gram staining, we finally determined that the patient died due to cerebral vascular rupture and hemorrhage caused by PACNS. This case illustrates the value and key points of autopsy in evaluating sudden deaths.

The genomic history of southwestern Chinese populations demonstrated massive population migration and admixture among proto-Hmong-Mien speakers and incoming migrants.

Southwest China was the crossroad for the initial settler people of East Asia, which shows the highest diversity in languages and genetics. This region played a significant role in the formation of the genetic makeup of the proto-Hmong-Mien-speaking people and in the north-to-south human expansion during the Neolithic-to-historic transformation. Their genetic history covering migration events and the admixture processes still needs to be further explored. Therefore, in the current study, we have generated genome-wide data from three genomic aspects covering autosomal, mitochondrial and Y-chromosomal regions in 260 Hmong-Mien, Tibeto-Burman, and Sinitic people from 29 different southwestern Chinese groups, and further analyzed them with 2676 published modern and ancient Eurasian genomes. Here, we have noticed a new southwestern East Asian genetic cline composed of the Hmong-Mien-specific ancestry enriched in modern Hmong and Pathen. This newly identified southern inland East Asian lineage contributed to a great extent of the gene pool in the modern southern East Asians. We also have observed genetic substructure among Hmong-Mien-speaking populations. The southern Hmong-Mien-speaking people showed more genetic affinity with modern Tai-Kadai/Austroasiatic people, while the northern Hmong-Mien speakers expressed a closer genetic connection with the Neolithic-to-modern northern East Asians. Moreover, southwestern Sinitic populations had a strong genomic affinity with the adjacent Hmong-Mien-speaking populations and the lowlander Tibeto-Burman-speaking populations, which suggested the large-scale genetic admixture occurred between them. Allele-sharing-based qpAdm/qpGraph results further confirmed that all included southwestern Chinese populations could be modeled as a mixed result of the major ancestry component from the northern millet farmers in the Yellow River basin and the minor ancestry component from the southern rice farmers in the Yangtze River basin. Usually, this newly identified Hmong-Mien-associated southern East Asian ancestry could improve our understanding of the full-scale genetic landscape of the evolutionary and admixture history of southwestern East Asians. Further ancient genomic studies from southeastern China are required to shed deeper light on our established phylogeny context.

Expression of airway smooth muscle contractile proteins in children with acute interstitial pneumonia.

The purpose of the present study was to investigate the expression of α-SMA and SM22α in airway smooth muscle (ASM) of bronchioles from children younger than 14 years who died of acute interstitial pneumonia (AIP). This is based upon the hypothesis that as contractile marker proteins α-SMA and SM22α can serve as an index of the overcontractile phenotype of ASM that is seen in AIP. Lung tissue samples of children were obtained from autopsies and divided into the AIP group (55.9% male and 44.1% female, between 0.4 and 132 months old, n = 34) and the control group (60% male and 40% female, between 2 and 156 months old, n = 10). We recorded the post-mortem interval (PMI), height, clinical symptoms and abdominal fat thickness (AFT) of each case. Haematoxylin-and-eosin-stained sections were used to examine the luminal area and observe the morphological changes in the bronchioles. Immunohistochemistry and Masson's trichrome staining were used to detect the expression of contractile marker proteins and the degree of pulmonary fibrosis respectively. Compared with the control group, the luminal areas of bronchioles in the AIP group were smaller (p < .001). The expression differences in α-SMA and SM22α between the two groups were statistically significant (p = .01 and p = .02 respectively). Also, there was no significant correlation of the contractile marker proteins expression with PMI, height, clinical symptoms and AFT. The collagen deposition difference in lung between the two groups was not statistically significant (p = .224). These findings suggest that enhancement of ASM contractile function appears to be involved in the death mechanism of children with AIP, which affords more insights into the understanding of AIP.

Population data and forensic efficiency of 21 autosomal STR loci included in AGCU EX22 amplification system in the Wanzhou Han population.

Autosomal short tandem repeats (STRs), widely distributed in the whole human genome, play an important role in personal identification and parentage testing. In this study, the allele frequencies and forensic efficiency parameters of 21 autosomal STR loci included in the AGCU EX22 kit were obtained from 433 Chinese Han individuals residing in the Wanzhou District in the north of Chongqing Municipality, Southwest China. No deviation from Hardy-Weinberg equilibrium was observed in all of the 21 STR loci. A total of 241 alleles were observed with allele frequencies ranging from 0.0011 to 0.5418. The cumulative power of discrimination and the cumulative probability of exclusion were 0.9999999999999999999999999 and 0.999999996, respectively. The results of genetic distance, neighbor-joining tree, principal component plots, and multidimensional scaling analysis revealed that the Wanzhou Han had more genetic differences when compared with Kazakh and Uyghur populations from Xinjiang than other included reference populations. In summary, the results in forensic characteristic analyses indicated that the 21 STRs are highly polymorphic and can be served as a useful tool in forensic routine practices. The population comparison indicated that close geographic or ethnic origin groups had a strong genetic affinity with each other.

Effects of spontaneous recurrent seizures on cognitive function via modulation of SNAREs expression.

PURPOSE: To explore whether soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) complexes are involved in cognitive dysfunction induced by spontaneous recurrent seizures (SRS). MATERIALS AND METHODS: An animal model of epilepsy was established by intraperitoneal injection of kainic acid (KA). Following the onset of SRS, the rats were divided into control group, KA-SRS group, KA+SRS group and KA+SRS+VAP group. Morris water maze and open field test were conducted to evaluate the cognitive function. Protein and mRNA levels of SNAREs complex were measured by Western-blot and RT-PCR, respectively. Besides, the Ca2+ concentration in the hippocampus was also detected. RESULTS: A delayed escape latency and a reduced number of platform crossings were found in the KA+SRS group. Meanwhile, a longer moving distance and time spent in central area were also observed during the open field test. Besides, the Ca2+ concentration in the hippocampus of the KA+SRS group was markedly increased. However, when compared with the KA+SRS group, all indices in the KA+SRS+VAP group were markedly improved. Moreover, the SNARE complexes in the hippocampus of the KA+SRS group were significantly increased when compared with both control group and KA+SRS+VAP group. CONCLUSIONS: Results of our study demonstrated that the cognitive dysfunction caused by SRS may be attributed to the modulation expression of SNARE complexes.

Genetic polymorphisms for 19 autosomal STR loci of Chongqing Han ethnicity and phylogenetic structure exploration among 28 Chinese populations.

The allele frequencies and forensic statistical parameters of 19 autosomal short tandem repeat (STR) loci (D8S1179, D21S11, D7S820, CSF1P0, D3S1358, THOl, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818, FGA, D6S1043, Penta D, Penta E, and D12S391) included in the Goldeneye™ DNA ID system 20A kit were obtained in 671 Chinese Han individuals residing in Chongqing, Southwest China. All 19 STR loci were identified in agreement with the Hardy-Weinberg equilibrium. A total of 238 alleles were observed with corresponding allele frequencies that varied from 0.0007 to 0.5119. The combined power of discrimination and the combined probability of exclusion for 19 STR loci in the Chongqing Han population were 0.99999999999999999999998954 and 0.99999998387, respectively. The findings indicated that the 19 autosomal STR loci were highly polymorphic in the Chongqing Han population and can be used as a powerful tool in personal identification and parentage testing. Our genetic study enriched the Chinese local forensic reference database. Population comparisons and phylogenetic analyses revealed that genetic heterogeneity widely existed among the Chongqing Han, Xinjiang Uyghur, and Kazakh populations as well as demonstrated that genetic similarity was tightly associated with those of close geographic origin or of the same ethnic origin.

Exploration of Clozapine-Induced Cardiomyopathy and Its Mechanism.

In this study, by pooling the clinical data of patients who died with a history of long-term clozapine use and by examining their hearts, it was found that long-term clozapine use can lead to cardiomyopathy and that its presentation resembles arrhythmogenic cardiomyopathy (ACM), i.e., it exhibits a predominantly right ventricular fatty infiltration with mild left ventricular damage. The transcriptomic data of rat cardiomyocytes after clozapine intervention were analyzed by transcriptomic approach to explore the causes of clozapine cardiomyopathy. The cause of clozapine cardiomyopathy was then explored by a transcriptomic approach, which revealed that its clozapine action on cardiomyocytes enriched cardiomyocyte-related differential genes in biological processes such as muscle development and response to hypoxia, as well as pathways such as fatty acid metabolism and cellular autophagy. Transcriptomic analysis showed that Egr1, Egr2, ler2, Jun, Mapk9, Nr1d2, Atf3, Bhlhe40, Crem, Cry1, Cry2, Dbp were hub genes for clozapine injury to the myocardium, and that these genes may play an important role in the myocardial ACM-like changes caused by clozapine. Combined with the results of pathological examination and transcriptomic analysis, it can be concluded that the long-term action of clozapine on cardiomyocytes leads to cellular autophagy and subsequent structural remodeling of the heart, and in the remodeling affects fatty acid metabolism, which eventually leads to ACM-like changes.

Forensic investigative genetic genealogy: expanding pedigree tracing and genetic inquiry in the genomic era.

Genetic genealogy provides crucial insights into the complex biological relationships within contemporary and ancient human populations by analyzing shared alleles and chromosomal segments that are identical by descent, to understand kinship, migration patterns, and population dynamics. Within forensic science, forensic investigative genetic genealogy (FIGG) has gained prominence by leveraging next-generation sequencing technologies and population-specific genomic resources, opening new investigative avenues. In this review, we synthesize current knowledge, underscore recent advancements, and discuss the growing role of FIGG in forensic genomics. FIGG has been pivotal in revitalizing dormant inquiries and offering new genetic leads in numerous cold cases. Its effectiveness relies on the extensive SNP profiles contributed by individuals from diverse populations to specialized genomic databases. Advances in computational genomics and the growth of human genomic databases have spurred a profound shift in the application of genetic genealogy across forensics, anthropology, and ancient DNA studies. As the field progresses, FIGG is evolving from a nascent practice into a more sophisticated and specialized discipline, shaping the future of forensic investigations.

Malaria resistance-related biological adaptation and complex evolutionary footprints inferred from one integrative Tai-Kadai-related genomic resource.

Pathogen‒host adaptative interactions and complex population demographical processes, including admixture, drift, and Darwen selection, have considerably shaped the Neolithic-to-Modern Western Eurasian population structure and genetic susceptibility to modern human diseases. However, the genetic footprints of evolutionary events in East Asia remain unknown due to the underrepresentation of genomic diversity and the design of large-scale population studies. We reported one aggregated database of genome-wide SNP variations from 796 Tai-Kadai (TK) genomes, including that of Bouyei first reported here, to explore the genetic history, population structure, and biological adaptative features of TK people from southern China and Southeast Asia. We found geography-related population substructure among TK people using the state-of-the-art population genetic structure reconstruction techniques based on the allele frequency spectrum and haplotype-resolved phased fragments. We found that the northern TK people from Guizhou harbored one TK-dominant ancestry maximized in the Bouyei people, and the southern TK people from Thailand were more influenced by Southeast Asians and indigenous people. We reconstructed fitted admixture models and demographic graphs, which showed that TK people received gene flow from ancient southern rice farmer-related lineages related to the Hmong-Mien and Austroasiatic people and from northern millet farmers associated with the Sino-Tibetan people. Biological adaptation focused on our identified unique TK lineages related to Bouyei, which showed many adaptive signatures conferring Malaria resistance and low-rate lipid metabolism. Further gene enrichment, the allele frequency distribution of derived alleles, and their correlation with the incidence of Malaria further confirmed that CR1 played an essential role in the resistance of Malaria in the ancient "Baiyue" tribes.

Double-bundle reconstruction results in superior clinical outcome than single-bundle reconstruction.

PURPOSE: To compare the short- and long-term clinical outcomes of the double-bundle (DB) anterior cruciate ligament (ACL) reconstruction with those of single-bundle (SB) ACL reconstruction. METHODS: An electronic search of the database PubMed (1966-September 2011), EMBASE (1984-September 2011), and Cochrane Controlled Trials Register (CENTRAL; 3rd Quarter, 2011) was undertaken to identify relevant studies. Main clinical outcomes were knee stability measurements including KT-1000 arthrometer measurement, Pivot shift test, and Lachman test, and clinical outcome measurements including International Knee Documentation Committee (IKDC), Lysholm knee score, Tegner activity score, and complications. RESULTS: Eighteen studies were finally included in this meta-analysis, which were all classified as high risk of bias according to the Collaboration's recommended tool. It is seen that compared to SB ACL reconstruction, DB ACL reconstruction results in a KT-1000 arthrometer outcome 0.63 and 1.00 mm closer to the normal knee in a short- and long-term follow-up, respectively. Our results also reveal that DB-treated patients have a significantly higher negative rate of the pivot shift test (p < 0.00001 and = 0.006 in a short- and long-term follow-up, respectively) and Lachman test (n.s. and p < 0.0001 in a short- and long-term follow-up, respectively) compared to SB-treated patients. As for the clinical outcome measurements, a significant difference is found between SB versus DB ACL reconstruction regarding the IKDC (p = 0.006 and < 0.0001 in a short- and long-term follow-up, respectively) and complications (p = 0.03), while there is no significant difference between the two groups regarding Lysholm knee score (n.s.) and Tegner activity score (n.s.). CONCLUSION: Overall, double-bundle ACL reconstruction yields better clinical outcomes when compared to single-bundle ACL reconstruction. LEVELS OF EVIDENCE: II.

Distinguished biological adaptation architecture aggravated population differentiation of Tibeto-Burman-speaking people.

Tibeto-Burman (TB) people have endeavored to adapt to the hypoxic, cold, and high-UV high-altitude environments in the Tibetan Plateau and complex disease exposures in lowland rainforests since the late Paleolithic period. However, the full landscape of genetic history and biological adaptation of geographically diverse TB-speaking people, as well as their interaction mechanism, remain unknown. Here, we generate a whole-genome meta-database of 500 individuals from 39 TB-speaking populations and present a comprehensive landscape of genetic diversity, admixture history, and differentiated adaptative features of geographically different TB-speaking people. We identify genetic differentiation related to geography and language among TB-speaking people, consistent with their differentiated admixture process with incoming or indigenous ancestral source populations. A robust genetic connection between the Tibetan-Yi corridor and the ancient Yellow River people supports their Northern China origin hypothesis. We finally report substructure-related differentiated biological adaptative signatures between highland Tibetans and Loloish speakers. Adaptative signatures associated with the physical pigmentation (EDAR and SLC24A5) and metabolism (ALDH9A1) are identified in Loloish people, which differed from the high-altitude adaptative genetic architecture in Tibetan. TB-related genomic resources provide new insights into the genetic basis of biological adaptation and better reference for the anthropologically informed sampling design in biomedical and genomic cohort research.

Interleukin-18 promoter polymorphism and asthma risk: a meta-analysis.

Some studies have shown that IL-18 was associated with aetiology and progression of asthma. However, the association between single-nucleotide polymorphisms -607C/A (rs1946518) and -137G/C (rs187238) located in the IL-18 gene promoter and asthma risk was still controversial and ambiguous. To derive a more precise effect on the association between these polymorphisms and asthma risk, we performed a meta-analysis based on the currently available evidence of the literature. A total of 5 studies with 1411 cases and 1525 controls for -607C/A polymorphism and 5 studies with 1883 cases and 6645 controls for -137G/C polymorphism were identified to perform a meta-analysis, up to October 2010. Summary ORs and corresponding 95% CIs for IL-18 polymorphisms and asthma were estimated using fixed- and random-effects models when appropriate. Heterogeneity and publication bias were evaluated. We found that individuals carrying AC/CC genotype of -607C/A polymorphism were associated with an increased asthma risk in recessive model (OR = 1.278; 95% CI, 1.073-1.522). However, no significant association was observed between -137G/C polymorphism and asthma risk under different contrast models. There was no evidence of publication bias. The present meta-analysis suggested that IL-18 -607C/A polymorphism in promoter region was associated with asthma risk.