Clinical, genetic profile and therapy evaluation of 11 Chinese pediatric patients with Fanconi-Bickel syndrome.

BACKGROUND: Fanconi-Bickel syndrome (FBS) is a rare autosomal recessive disorder characterized by impaired glucose and galactose utilization as well as proximal renal tubular dysfunction. METHODS: Clinical, biochemical, genetic, treatment, and follow-up data for 11 pediatric patients with FBS were retrospectively analysed. RESULTS: Hepatomegaly (10/11), short stature (10/11) and hypophosphataemic rickets (7/11) were the most common initial symptoms. At diagnosis, all patients had decreased fasting blood glucose (FBG), plasma bicarbonate (HCO3-) and serum phosphorus, as well as elevated liver transaminases, alkaline phosphatase (AKP) and proximal renal tubular dysfunction. Two infant patients were misdiagnosed with transient neonatal diabetes mellitus. After therapy with uncooked cornstarch and conventional rickets treatment, remission of hepatomegaly was observed in all patients, with significant improvements in pre-prandial blood glucose, liver transaminases, triglyceride, plasma HCO3- and AKP (p < 0.05). At the last follow-up, 5/7 patients with elevated AKP had nephrocalcinosis. The mean height standard deviation score (Ht SDS) of eight patients with regular treatment increased from - 4.1 to -3.5 (p = 0.02). Recombinant human growth hormone (rhGH) was administered to 4/9 patients, but their Ht SDS did not improve significantly (p = 0.13). Fourteen variants of the SLC2A2 gene were identified, with six being novel, among which one was recurrent: c.1217T > G (p.L406R) (allele frequency: 4/22, 18%). Patients with biallelic missense variants showed milder metabolic acidosis than those with null variants. Two of five patients from nonconsanguineous families with rare homozygous variations showed 5.3 Mb and 36.6 Mb of homozygosity surrounding the variants, respectively; a region of homozygosity (ROH) involving the entire chromosome 3 covering the SLC2A2 gene, suggesting uniparental disomy 3, was detected in one patient. CONCLUSIONS: Early diagnosis of FBS is difficult due to the heterogeneity of initial symptoms. Although short stature is a major issue of treatment for FBS, rhGH is not recommended in FBS patients who have normal GH stimulation tests. Patients with biallelic null variants may require alkali supplementation since urine bicarbonate loss is genetically related. ROH is a mechanism for rare homozygous variants of FBS in nonconsanguineous families.

Quality evaluation of metabolic and bariatric surgical guidelines.

Objective: To evaluate the quality of surgical guidelines on bariatric/metabolic surgery. Methods: Four independent reviewers used the AGREE II (The Appraisal of Guidelines for Research and Evaluation II) tool to assess the methodological quality of the included guidelines and conducted a comparative analysis of the main recommendations for surgical methods of these guidelines. Results: Nine surgical guidelines were included in this study. Five articles with AGREE II scores over 60% are worthy of clinical recommendation. The field of rigor of development was relatively low, with an average score of 50.82%. Among 15 key recommendations and the corresponding best evidence in the guidelines, only 4 key recommendations were grade A recommendations. Conclusions: The quality of metabolic and bariatric guidelines is uneven, and there is much room for improvement.

A new genus of pliopithecoid from the late Early Miocene of China and its implications for understanding the paleozoogeography of the Pliopithecoidea.

A diversity of pliopithecoids is known from Miocene localities in Europe, but until recently, this group was relatively poorly represented in China. However, new discoveries have shown that Chinese pliopithecoids were taxonomically diverse and geographically widespread. The earliest pliopithecoids in China (and Eurasia) are Dionysopithecus and Platodontopithecus from the Early Miocene of Sihong, Jiangsu (∼19-18 Ma). During the Middle Miocene (∼15-12 Ma), several species of pliopithecoids are recorded at localities in Gansu Province (Laogou), Inner Mongolia (Damiao), Xinjiang Uygur Autonomous Region (Tieersihabahe), and Ningxia Hui Autonomous Region (Tongxin). Finally, a late-surviving anapithecine crouzeliid, Laccopithecus robustus, is known from the Late Miocene (∼7 Ma) of Shihuiba in Yunnan, which postdates the extinction of pliopithecoids in Europe (during MN 10). Paleontological investigations at a late Early Miocene locality near Fanchang in Anhui Province have yielded a large sample of isolated teeth (more than one hundred) of a previously unknown species of pliopithecoid. The associated micromammals indicate an age contemporaneous with the Shanwang Formation in Shandong Province (MN 3-4, ∼18-17 Ma). All of the permanent teeth are represented except for I2. With its unique suite of dental features, the Fanchang pliopithecoid can be attributed to a new species and genus. Shared derived features of the lower molars confirm that the Fanchang pliopithecoid has its closest affinities with European crouzeliids, but a number of primitive traits indicate that it is a stem member of the clade. The evidence points to China as an important center for the early diversification of pliopithecoids. Contrary to previous zoogeographic scenarios, the occurrence of an early crouzeliid in China implies that the Pliopithecidae and Crouzeliidae may have diverged from a stem pliopithecoid in Asia during the Early Miocene before their arrival in Europe.

Ancient DNA indicates human population shifts and admixture in northern and southern China.

Human genetic history in East Asia is poorly understood. To clarify population relationships, we obtained genome-wide data from 26 ancient individuals from northern and southern East Asia spanning 9500 to 300 years ago. Genetic differentiation in this region was higher in the past than the present, which reflects a major episode of admixture involving northern East Asian ancestry spreading across southern East Asia after the Neolithic, thereby transforming the genetic ancestry of southern China. Mainland southern East Asian and Taiwan Strait island samples from the Neolithic show clear connections with modern and ancient individuals with Austronesian-related ancestry, which supports an origin in southern China for proto-Austronesians. Connections among Neolithic coastal groups from Siberia and Japan to Vietnam indicate that migration and gene flow played an important role in the prehistory of coastal Asia.

26Al/10Be Burial Dating of the Middle Pleistocene Yiyuan Hominin Fossil Site, Shandong Province, Northern China.

The Yiyuan hominin fossil site is one of the few localities in China where a partial skullcap and several loose teeth of Homo erectus have been discovered. Yiyuan was previously assigned broadly to the Middle Pleistocene by biostratigraphical correlation and ESR/U-series dating. Here, we report the first application of a radio-isotopic dating method to the site. 26Al/10Be burial dating results derived from two sand samples from the fossiliferous deposits show that the hominin fossils can be confidently dated to 0.64 ± 0.08 Ma (million years ago). The reliability of this age is supported by the zero age of modern fluvial sediment near the cave. Our result is consistent with the age estimation based on biostratigraphic correlation and supports the argument that the Yiyuan and Zhoukoudian Locality 1 H. erectus fossils are contemporaneous. The results presented here, along with other recent chronological studies on Chinese Middle Pleistocene hominin sites, indicate that the time span from 600-400 ka (thousand years ago) is a critical period for human evolution in East Asia. Importantly, this time bracket includes several major climatic changes that would have influenced hominins, both morphologically and behaviorally.

Hominin teeth from the Middle Pleistocene site of Yiyuan, Eastern China.

In 1981-1982, some hominin fossils, including a relatively complete skull and seven isolated teeth, were recovered from the Middle Pleistocene site of Yiyuan in Eastern China. In the present study we provide a detailed metric and morphological comparison of the Yiyuan dental sample in order to characterize better the variability of the human populations that inhabited China during the Middle Pleistocene. Aside from taxonomic and phylogenetic questions, the lack of understanding and/or knowledge about the morphological variability of these populations have caused concern about the human versus non-human nature of some of the hominin dental remains found in East Asia during the Early and the Middle Pleistocene. Thus, our study aims to present a detailed description and comparison of the Yiyuan isolated teeth to 1) discuss and support their human nature and 2) to explore their taxonomic affinities with regard to other penecontemporaneous populations from Asia. Our results clearly differentiate the Yiyuan sample from Pongo specimens and support a human attribution for the Yiyuan material. Our analyses also suggest that the Yiyuan teeth form a morphologically coherent group together with samples from Zhoukoudian, Chaoxian and Hexian. They are different from the more derived specimens from Panxian Dadong, suggesting a pattern of biogeographic isolation and different evolutionary trends between northern and southern China during the Middle Pleistocene. In addition, and despite sharing a common morphological bauplan with Homo erectus sensu stricto (s.s.), the Yiyuan, Zhoukoudian and Hexian teeth are also different from the Indonesian Early Pleistocene samples. In particular, the expression of a highly crenulated or dendritic enamel-dentine surface could be unique to these groups. Our study supports the notion that the taxonomy of the Pleistocene hominins from Asia may have been oversimplified. Future studies should explore the variability of the Asian specimens and reconsider whether all the samples can be attributed to H. erectus s.s.

A revised timescale for human evolution based on ancient mitochondrial genomes.

BACKGROUND: Recent analyses of de novo DNA mutations in modern humans have suggested a nuclear substitution rate that is approximately half that of previous estimates based on fossil calibration. This result has led to suggestions that major events in human evolution occurred far earlier than previously thought. RESULTS: Here, we use mitochondrial genome sequences from ten securely dated ancient modern humans spanning 40,000 years as calibration points for the mitochondrial clock, thus yielding a direct estimate of the mitochondrial substitution rate. Our clock yields mitochondrial divergence times that are in agreement with earlier estimates based on calibration points derived from either fossils or archaeological material. In particular, our results imply a separation of non-Africans from the most closely related sub-Saharan African mitochondrial DNAs (haplogroup L3) that occurred less than 62-95 kya. CONCLUSIONS: Though single loci like mitochondrial DNA (mtDNA) can only provide biased estimates of population divergence times, they can provide valid upper bounds. Our results exclude most of the older dates for African and non-African population divergences recently suggested by de novo mutation rate estimates in the nuclear genome.

A new oviraptorid (Dinosauria: Theropoda) from the Upper Cretaceous of southern China.

This paper describes a new oviraptorid dinosaur taxon, Ganzhousaurus nankangensis gen. et sp. nov., based on a specimen collected from the Upper Cretaceous Nanxiong Formation of Nankang County, Ganzhou City, Jiangxi Province, southern China. This new taxon is distinguishable from other oviraptorids based on the following unique combination of primitive and derived features: relatively shallow dentary; absence of fossa or pneumatopore on lateral surface of dentary; weakly downturned anterior mandibular end; shallow depression immediately surrounding anterior margin of external mandibular fenestra; external mandibular fenestra subdivided by anterior process of surangular; dentary posteroventral process slightly twisted and positioned on mandibular ventrolateral surface; shallow longitudinal groove along medial surface of dentary posteroventral process; angular anterior process wider transversely than deep dorsoventrally; sharp groove along ventrolateral surface of angular anterior process; ventral border of external mandibular fenestra formed mainly by angular; ventral flange along distal half of metatarsal II; and arctometatarsal condition absent. Phylogenetic analysis places Ganzhousaurus nankangensis gen. et sp. nov. in the clade Oviraptoridae, together with Oviraptor, Citipati, Rinchenia and the unnamed Zamyn Khondt oviraptorid.