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Sex chromosomes display remarkable diversity and variability among vertebrates. Compared with research on the X/Y and Z/W chromosomes, which have long evolutionary histories in mammals and birds, studies on the sex chromosomes at early evolutionary stages are limited. Here, we precisely assembled the genomes of homozygous XX female and YY male Lanzhou catfish (Silurus lanzhouensis) derived from an artificial gynogenetic family and a self-fertilized family, respectively. Chromosome 24 (Chr24) was identified as the sex chromosome based on resequencing data. Comparative analysis of the X and Y chromosomes showed an approximate 320 kb Y-specific region with a Y-specific duplicate of anti-Mullerian hormone type II receptor (amhr2y), which is consistent with findings in 2 other Silurus species but on different chromosomes (Chr24 of Silurus meridionalis and Chr5 of Silurus asotus). Deficiency of amhr2y resulted in male-to-female sex reversal, indicating that amhr2y plays a male-determining role in S. lanzhouensis. Phylogenetic analysis and comparative genomics revealed that the common sex-determining gene amhr2y was initially translocated to Chr24 of the Silurus ancestor along with the expansion of transposable elements. Chr24 was maintained as the sex chromosome in S. meridionalis and S. lanzhouensis, whereas a sex-determining region transition triggered sex chromosome turnover from Chr24 to Chr5 in S. asotus. Additionally, gene duplication, translocation, and degeneration were observed in the Y-specific regions of Silurus species. These findings present a clear case for the early evolutionary trajectory of sex chromosomes, including sex-determining gene origin, repeat sequence expansion, gene gathering and degeneration in sex-determining region, and sex chromosome turnover., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

G-quadruplexes (G4s) are non-canonical four-stranded structures and are emerging as novel genetic regulatory elements. However, a comprehensive genomic annotation of endogenous G4s (eG4s) and systematic characterization of their regulatory network are still lacking, posing major challenges for eG4 research. Here, we present EndoQuad (https://EndoQuad.chenzxlab.cn/) to address these pressing issues by integrating high-throughput experimental data. First, based on high-quality genome-wide eG4s mapping datasets (human: 1181; mouse: 24; chicken: 2) generated by G4 ChIP-seq/CUT&Tag, we generate a reference set of genome-wide eG4s. Our multi-omics analyses show that most eG4s are identified in one or a few cell types. The eG4s with higher occurrences across samples are more structurally stable, evolutionarily conserved, enriched in promoter regions, mark highly expressed genes and associate with complex regulatory programs, demonstrating higher confidence level for further experiments. Finally, we integrate millions of functional genomic variants and prioritize eG4s with regulatory functions in disease and cancer contexts. These efforts have culminated in the comprehensive and interactive database of experimentally validated DNA eG4s. As such, EndoQuad enables users to easily access, download and repurpose these data for their own research. EndoQuad will become a one-stop resource for eG4 research and lay the foundation for future functional studies., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Context: To date there is no study on the feasibility of radiofrequency ablation (RFA) for papillary thyroid microcarcinomas (PTMCs) with BRAF V600E mutation., Objective: This study was designed to evaluate the efficiency, safety, and prognosis of ultrasound (US)-guided percutaneous RFA for unifocal PTMCs with BRAF V600E mutation., Materials and Methods: Sixty patients with 60 unifocal BRAF V600E mutation-positive PTMCs who received US-guided RFA between January 2020 and December 2021 were retrospectively analyzed. The mean maximum PTMC tumor diameter was 5.8 ± 1.7 mm (range, 2.5-10.0 mm). All PTMCs were pathologically confirmed by fine needle aspiration or core needle biopsy, and BRAF V600E mutation was confirmed to be positive by real-time fluorescent quantitative polymerase chain reaction. Contrast-enhanced ultrasound (CEUS) was performed immediately after RFA to evaluate whether PTMCs were extendedly ablated. Ultrasound was performed 1, 3, 6, and 12 months after RFA and every 6 months thereafter to evaluate the changes in the ablation zone, local recurrence, and cervical lymph node metastasis (LNM). The complications were recorded and evaluated., Results: Extended ablation was achieved in all enrolled patients. The ablation zone sizes increased immediately after RFA compared with those of tumors before treatment. One month later, the ablation zone sizes were smaller than immediately after RFA. At the last follow-up assessment, 42 nodules (70.0%) completely disappeared and the ablation zones of 18 nodules (30.0%) showed fissure-like changes. No local recurrence or cervical LNM was detected. Voice change (1.7%) was the only major complication., Conclusion: RFA is effective and safe in treating unifocal PTMCs with BRAF V600E mutation, especially when surgery is not feasible or refused by patients who are unwilling to continue active surveillance., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Nasopharyngeal carcinoma (NPC) is closely associated with genetic factors and Epstein-Barr virus infection, showing strong familial aggregation. Individuals with a family history suffer elevated NPC risk, requiring effective genetic counseling for risk stratification and individualized prevention., Methods: We performed whole-exome sequencing on 502 familial NPC patients and 404 unaffected relatives and controls. We systematically evaluated the established cancer predisposition genes and investigated novel NPC susceptibility genes, making comparisons with 21 other familial cancers in the UK biobank (N = 5218)., Results: Rare pathogenic mutations in the established cancer predisposition genes were observed in familial NPC patients, including ERCC2 (1.39%), TP63 (1.00%), MUTYH (0.80%), and BRCA1 (0.80%). Additionally, 6 novel susceptibility genes were identified. RAD54L, involved in the DNA repair pathway together with ERCC2, MUTYH, and BRCA1, showed the highest frequency (4.18%) in familial NPC. Enrichment analysis found mutations in TP63 were enriched in familial NPC, and RAD54L and EML2 were enriched in both NPC and other Epstein-Barr virus-associated cancers. Besides rare variants, common variants reported in the studies of sporadic NPC were also associated with familial NPC risk. Individuals in the top quantile of common variant-derived genetic risk score while carrying rare variants exhibited increased NPC risk (odds ratio = 13.47, 95% confidence interval = 6.33 to 28.68, P = 1.48 × 10-11); men in this risk group showed a cumulative lifetime risk of 24.19%, much higher than those in the bottom common variant-derived genetic risk score quantile and without rare variants (2.04%)., Conclusions: This study expands the catalog of NPC susceptibility genes and provides the potential for risk stratification of individuals with an NPC family history., (© The Author(s) 2022. Published by Oxford University Press.)

Unisexual animals are commonly found in some polyploid species complexes, and most of these species have had a long evolutionary history. However, their method for avoiding genomic decay remains unclear. The polyploid Carassius complex naturally comprises the sexual amphidiploid C. auratus (crucian carp or goldfish) (AABB) and the gynogenetic amphitriploid C. gibelio (gibel carp) (AAABBB). Recently, we developed a fertile synthetic amphitetraploid (AAAABBBB) male from C. gibelio by incorporating a C. auratus genome. In this study, we generated novel amphitriploids (AAABBB) by backcrossing the amphitetraploid male with the amphidiploid C. auratus. Whole-genome resequencing revealed the genomic changes, including recombination and independent assortment between homologs of C. gibelio and C. auratus. The fertility, sex determination system, oocyte development, and fertilization behaviors of the novel amphitriploids were investigated. Approximately 80% of the novel amphitriploid females recovered the unisexual gynogenesis ability. Intriguingly, two types of primary oocyte (with and without homolog synapsis) were discovered, and their distinct development fates were observed. Type I oocytes entered apoptosis due to improper synaptonemal complex assembly and incomplete double-strand break repair, whereas subsequent type II oocytes bypassed meiosis through an alternative ameiotic pathway to develop into mature eggs. Moreover, gynogenesis was stabilized in their offspring, and a new array of diverse gynogenetic amphitriploid clones was produced. These revealed genomic changes and detailed cytological data provide comprehensive evidence that changes in ploidy drive unisexual and sexual reproduction transition, thereby resulting in genomic diversity and allowing C. gibelio avoid genomic decay., (© The Author(s) 2022. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

Evolutionary fates of duplicated genes have been widely investigated in many polyploid plants and animals, but research is scarce in recurrent polyploids. In this study, we focused on foxl2, a central player in ovary, and elaborated the functional divergence in gibel carp (Carassius gibelio), a recurrent auto-allo-hexaploid fish. First, we identified three divergent foxl2 homeologs (Cgfoxl2a-B, Cgfoxl2b-A, and Cgfoxl2b-B), each of them possessing three highly conserved alleles and revealed their biased retention/loss. Then, their abundant sexual dimorphism and biased expression were uncovered in hypothalamic-pituitary-gonadal axis. Significantly, granulosa cells and three subpopulations of thecal cells were distinguished by cellular localization of CgFoxl2a and CgFoxl2b, and the functional roles and the involved process were traced in folliculogenesis. Finally, we successfully edited multiple foxl2 homeologs and/or alleles by using CRISPR/Cas9. Cgfoxl2a-B deficiency led to ovary development arrest or complete sex reversal, whereas complete disruption of Cgfoxl2b-A and Cgfoxl2b-B resulted in the depletion of germ cells. Taken together, the detailed cellular localization and functional differences indicate that Cgfoxl2a and Cgfoxl2b have subfunctionalized and cooperated to regulate folliculogenesis and gonad differentiation, and Cgfoxl2b has evolved a new function in oogenesis. Therefore, the current study provides a typical case of homeolog/allele diversification, retention/loss, biased expression, and sub-/neofunctionalization in the evolution of duplicated genes driven by polyploidy and subsequent diploidization from the recurrent polyploid fish., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

Cold stress profoundly affects plant growth and development and is a key factor affecting the geographic distribution and evolution of plants. Plants have evolved adaptive mechanisms to cope with cold stress. Here, through the genomic analysis of Arabidopsis, three Brassica species and 17 other representative species, we found that both cold-related genes ( CRGs ) and their collinearity were preferentially retained after polyploidization followed by genome instability, while genome-wide gene sets exhibited a variety of other expansion mechanisms. The cold-related regulatory network was increased in Brassicaceae genomes, which were recursively affected by polyploidization. By combining our findings regarding the selective retention of CRGs from this ecological genomics study with the available knowledge of cold-induced chromosome doubling, we hypothesize that cold stress may have contributed to the success of polyploid plants through both increasing polyploidization and selectively maintaining CRGs during evolution. This hypothesis requires further biological and ecological exploration to obtain solid supporting evidence, which will potentially contribute to understanding the generation of polyploids and to the field of ecological genomics., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s) 2020.)

Allopolyploidization plays an important role in speciation, and some natural or synthetic allopolyploid fishes have been extensively applied to aquaculture. Although genetic and epigenetic inheritance and variation associated with plant allopolyploids have been well documented, the relative research in allopolyploid animals is scarce. In this study, the genome constitution and DNA methylation inheritance in a newly synthetic allopolyploid of gynogenetic gibel carp were analyzed. The incorporation of a whole genome of paternal common carp sperm in the allopolyploid was confirmed by genomic in situ hybridization, chromosome localization of 45S rDNAs, and sequence comparison. Pooled sample-based methylation sensitive amplified polymorphism (MSAP) revealed that an overwhelming majority (98.82%) of cytosine methylation patterns in the allopolyploid were inherited from its parents of hexaploid gibel carp clone D and common carp. Compared to its parents, 11 DNA fragments in the allopolyploid were proved to be caused by interindividual variation, recombination, deletion, and mutation through individual sample-based MSAP and sequencing. Contrast to the rapid and remarkable epigenetic changes in most of analyzed neopolyploids, no cytosine methylation variation was detected in the gynogenetic allopolyploid. Therefore, the newly synthetic allopolyploid of gynogenetic gibel carp combined genomes from its parents and maintained genetic and epigenetic stability after its formation and subsequently seven successive gynogenetic generations. Our current results provide a paradigm for recurrent polyploidy consequences in the gynogenetic allopolyploid animals.

Background: A previous study provided evidence for a genetic association between PPP2CA on 5q31.1 and systemic lupus erythematosus (SLE) across multi-ancestral cohorts, but failed to find significant evidence for an association in the Han Chinese population., Objectives: To explore the association between this locus and SLE using data from our previously published genome-wide association study (GWAS)., Methods: Single-nucleotide polymorphisms (SNPs) rs7726414 and rs244689 (near TCF7 and PPP2CA in 5q31.1) were selected as candidate independent associations from a large-scale study in a Han Chinese population consisting of 1047 cases and 1205 controls. Subsequently, 3509 cases and 8246 controls were genotyped in two further replication studies. We then investigated the SNPs' associations with SLE subphenotypes and gene expression in peripheral blood mononuclear cells., Results: Highly significant associations with SLE in the Han Chinese population were detected for SNPs rs7726414 and rs244689 by combining the genotype data from our previous GWAS and two independent replication cohorts. Further conditional analyses indicated that these two SNPs contribute to disease susceptibility independently. A significant association with SLE, age at diagnosis < 20 years, was found for rs7726414 (P = 0·001). The expression levels of TCF7 and PPP2CA messenger RNA in patients with SLE were significantly decreased compared with those in healthy controls., Conclusions: This study found evidence for multiple associations with SLE in 5q31.1 at genome-wide levels of significance for the first time in a Han Chinese population, in a combined genotype dataset. These findings suggest that variants in the 5q31.1 locus not only provide novel insights into the genetic architecture of SLE, but also contribute to the complex subphenotypes of SLE., (© 2017 British Association of Dermatologists.)

Study Question: What is the difference in vaginal-length gain and resumption of menstruation following cervicovaginal reconstruction using split-thickness skin (STS) graft versus small intestinal submucosa (SIS) graft for patients with congenital vaginal and cervical aplasia?, Summary Answer: No difference was found in the number of patients who resumed menstruation between the two groups; however, significantly greater vaginal-length gain was found in the STS group., What Is Already Known: Hysterectomy and vaginoplasty are typically recommended for patients without a cervix or without a sufficient cervix to avoid postoperative re-obstruction. Advances in surgical techniques have enabled the use of autologous tissues or heterologous biological grafts for reconstructive procedures, allowing patients undergoing these procedures to preserve the possibility of conception., Study Design, Size, Duration: This was a retrospective study of 26 women who were diagnosed with congenital vaginal and cervical aplasia with a functional endometrial cavity and underwent cervicovaginal reconstruction using STS or SIS grafts between January 2012 and October 2015 at the Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China., Participants/materials, Setting, Method: 15 women underwent cervicovaginal reconstruction using SIS graft and 11 underwent cervicovaginal reconstruction using STS graft. Clinical characteristics, perioperative data, resumption of menstruation, vaginal stenosis, length of the neovagina, vaginal-length gain, stricture of the cervix and body image were postoperatively assessed., Main Results and the Role of Chance: At a median follow-up of 21 (2-46) months, all but one of the patients experienced relief of abdominal pain and resumed menstruation. Re-obstruction of the cervix occurred in only one patient in the SIS group. The SIS group reported significantly higher body image scores and cosmetic satisfaction. Although the two groups had a similar vaginal length before surgery, the vaginal-length gain was significantly greater in the STS group (4.9 ± 1.7 cm in the SIS group versus 7.5 ± 0.7 cm in the STS group, P = 0.004) and the neovagina length at 6 months post-operation was significantly shorter in the SIS group (6.5 ± 0.7 cm in SIS the group versus 8.0 ± 0.5 cm in the STS group, P < 0.0001)., Limitations, Reasons for Caution: Due to a lack of long-term follow-up, patient satisfaction with sex life, pregnancy rates and outcomes after the two approaches require further evaluation., Wider Implications of the Findings: Combined laparoscopic and vaginal cervicovaginal reconstruction using SIS or STS graft is a safe and effective treatment for preserving uterus function in women with congenital vaginal and cervical aplasia. However, SIS graft must still be improved to achieve satisfactory vaginal length., Study Funding/competing Interests: This study was supported by the Chinese National Nature Sciences Foundation (grant number 81471416) and the National Key Clinical Faculty Construction Program of China. No competing interests are declared., Trial Registration Number: N/A., (© The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Well-conducted meta-analyses (MAs) are considered as one of the best sources of clinical evidence for treatment decision. MA with methodological flaws may introduce bias and mislead evidence users. The aim of this study is to investigate the characteristics and methodological quality of MAs on diabetes mellitus (DM) treatments., Design: Systematic review., Methods: Cochrane Database of Systematic Review and Database of Abstract of Reviews of Effects were searched for relevant MAs. Assessing methodological quality of systematic reviews (AMSTAR) tool was used to evaluate the methodological quality of included MAs. Logistic regression analysis was used to identify association between characteristics of MA and AMSTAR results., Results: A total of 252 MAs including 4999 primary studies and 13,577,025 patients were included. Over half of the MAs (65.1%) only included type 2 DM patients and 160 MAs (63.5%) focused on pharmacological treatments. About 89.7% MAs performed comprehensive literature search and 89.3% provided characteristics of included studies. Included MAs generally had poor performance on the remaining AMSTAR items, especially in assessing publication bias (39.3%), providing lists of studies (19.0%) and declaring source of support comprehensively (7.5%). Only 62.7% MAs mentioned about harm of interventions. MAs with corresponding author from Asia performed less well in providing MA protocol than those from Europe., Conclusions: Methodological quality of MA on DM treatments was unsatisfactory. There is considerable room for improvement, especially in assessing publication bias, providing lists of studies and declaring source of support comprehensively. Also, there is an urgent need for MA authors to report treatment harm comprehensively., (© 2016 European Society of Endocrinology.)

Sex is generally determined by sex chromosomes in vertebrates, and sex chromosomes exhibit the most rapidly-evolving traits. Sex chromosome evolution has been revealed previously in numerous cases, but the association between sex chromosome origin and the reproduction mode transition from unisexual to sexual reproduction remains unclear. Here, we have isolated a male-specific sequence via analysis of amplified fragment length polymorphism from polyploid gibel carp (Carassius gibelio), a species that not only has the ability to reproduce unisexually but also contains males in wild populations. Subsequently, we have found through FISH analysis that males have several extra microchromosomes with repetitive sequences and transposable elements when compared to females. Moreover, we produced sex-reversed physiological females with a male-specific marker by using estradiol hormone treatment, and two gynogenetic families were established from them. In addition, the male incidence rates of two gynogenetic families were revealed to be closely associated with the extra microchromosome number of the sex-reversed physiological females. These results suggest that the extra microchromosomes in males might resemble a common feature of sex chromosomes and might play a significant role in male determination during the evolutionary trajectory of the reproduction mode transition from unisexual to sexual reproduction in the polyploid fish., (Copyright © 2016 by the Genetics Society of America.)

Study Question: Can vaginoplasty in patients with Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) be achieved using an acellular porcine small intestinal submucosa (SIS) graft?, Summary Answer: Vaginoplasty using SIS graft was successfully achieved in women with MRKHS, and the anatomical and functional outcomes of this procedure were comparable to those of laparoscopic peritoneal vaginoplasty., What Is Known Already: There is a great variety of vaginal reconstruction techniques, which suggests there is no single superior surgical technique., Study Design, Size, Duration: This prospective observational study included 34 patients with congenital vaginal agenesis who underwent vaginoplasty using SIS graft (the SIS group) between December 2011 and July 2013, and 41 patients with the same disease who underwent laparoscopic peritoneal vaginoplasty (the Davydov group) between January 2008 and July 2013., Participants/materials, Setting, Methods: Patient and surgical data, follow-up information, and the female sexual function index (FSFI) scores in the two groups were analysed and compared., Main Results and the Role of Chance: Compared with the laparoscopic Davydov procedure, the operating time of vaginoplasty using SIS graft was significantly shorter, and the estimated blood loss was significantly less. Patients in the SIS group had an earlier return of bowel activity, and an earlier return to work. However, the total cost in the SIS group was significantly higher than that in the Davydov group due to the cost of the SIS graft ($3525 per graft). Most patients (28/34 in the SIS group and 37/41 in the laparoscopic Davydov group) returned for their follow-up 9 months post-surgery. The mean length of the neovagina in the SIS group seemed slightly shorter than that in the Davydov group (6.8 ± 0.9 cm versus 7.3 ± 1.3 cm, P = 0.081). Thirteen patients (46%) in the SIS group and 11 (29%) in the Davydov group had a neovagina <7 cm long (P = 0.453), whereas 4 patients (14%) in the SIS group and 3 patients (8%) in the Davydov group had a neovagina <6 cm long (P = 0.201). Sixteen patients in the SIS group and 25 in the Davydov group subsequently had a sexual partner and became sexually active. Four patients in the SIS group and six in the Davydov group reported low total FSFI scores (≤23). There was no statistically significant difference in the total FSFI scores and the scores of all six domains of the FSFI between the two groups. The average time of continuous mould wearing in the SIS group was statistically significantly longer than that in the Davydov group (7.8 ± 3.3 months versus 4.8 ± 1.6 months, P = 0.001). In the patients with a neovaginal length of ≥6 cm, the FSFI score of the women (26.6 ± 2.3 versus 21.5 ± 1.5, P < 0.001) and the satisfactory score of their partner (8.6 ± 1.2 versus 6.6 ± 1.2, P < 0.001) were both statistically significantly higher than patients with a neovaginal length of <6 cm., Limitations, Reasons for Caution: The main limitation of this study is that it is non-randomized. Further randomized studies are warranted to compare the effects of these two procedures., Wider Implications of the Findings: Despite the need to wear a mould for longer, vaginoplasty using SIS graft provides an attractive, alternative treatment for women with MRKHS., Study Funding/competing Interests: This study was supported by the Chinese National Nature Sciences Foundation (grant number 81471416) and the National Key Clinical Faculty Construction Program of China. No competing interests are declared., Trial Registration Number: N/A., (© The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Study Question: Can surgical reconstruction of the cervix and vagina in patients be achieved using an acellular porcine small intestinal submucosa (SIS) graft?, Summary Answer: Our experiences of combined laparoscopic and vaginal cervicovaginal reconstruction using an SIS graft in eight patients were positive, with successful reconstruction and no complications, cervical stenosis or vaginal stenosis., What Is Known Already: In patients with agenesis and dysgenesis of the uterine cervix and vagina, surgical reconstruction of the internal genitalia is a challenging problem for gynecologists. Hysterectomy with the creation of an artificial vagina was the treatment of choice in the 1990s. Recently, conservative management has been gradually adopted to avoid extirpation of the uterus, including the canalization techniques, the uterovaginal anastomosis and the reconstruction of cervical and vaginal agenesis with some autologous tissues., Study Design, Size, Duration: This prospective observational study from January 2012 to March 2013 included 8 patients aged 10-18 years with malformation of the cervix (1 with cervical agenesis, 1 with a cervical body consisting of a fibrous band and 6 with obstruction of the cervical os) and vagina (4 with complete vaginal aplasia and 4 with a 1-3 cm long vaginal pouch) diagnosed by physical examination and magnetic resonance imaging., Participants/materials, Setting, Methods: Eight patients underwent combined laparoscopic and vaginal cervicovaginal reconstruction using an SIS graft during the end of menstruation. A T-shaped intrauterine device connected with a 14-French Foley catheter was inserted into the uterine cavity to keep the newly created cervix patent, and then a permanent lower uterine cerclage was placed. Patients were assessed post-operatively at 1, 2, 4, 6, 12 and 15 months, and data on menstruation and the morphology of the neovagina and cervix were recorded., Main Results and the Role of Chance: The mean ± SD age of the patients was 14.5 ± 2.8 (10-18) years. All patients had a history of cyclic abdominal pain, and the average delay in diagnosis was 4.5 ± 4.0 (0-12) months. One patient had a previous history of unsuccessful attempt at canalization and two post-operative hematometra drainages before referral. The mean operating time was 201 ± 67 (120-330) min, with a mean estimated blood loss of 157 ± 154 (30-500) ml. The first case was converted to laparotomy, and the others were successfully completed. None of the patients had a complication or required blood transfusion. All the patients showed resumption of menstruation. The patients were followed for 8 ± 4 (4-15) months, and no cervical or vaginal stenosis occurred in any of the cases., Limitations, Reasons for Caution: The sample size of this study was small. A larger study that compared this method with previous techniques regarding the complication and success rates would increase the value of the study., Wider Implications of the Findings: A combined laparoscopic and vaginal cervicovaginal reconstruction with an SIS graft is a potential alternative to the management of congenital agenesis and dysgenesis of uterine cervix and vagina., Study Funding/competing Interest(s): The work was supported by National Key Clinical Faculty Construction Program of China. No competing interests are declared.

Ikaros family zinc finger 1, encoded by IKZF1, are lymphoid-restricted zinc finger transcription factors that share common N-terminal Kruppel-like zinc finger DNA-binding domain. IKZF1 play multiple important roles on regulators of lymphocyte differentiation and hematological tumor suppressor. Our genome-wide association (GWA) studies in systemic lupus erythematosus (SLE) independently identified genetic variants in IKZF1 associated with SLE, which are supported by other studies. Previous studies found that lower expression of IKZF1 may play critical roles in activating some signal pathways involved in SLE, such as signal transducers and activators of transcription (STAT)4 and interferon pathways. In addition, IKZF1 has been implicated in roles involved in some hematologic traits or abnormalities, such as erythrocyte measures, myelofibrosis, and acute lymphoblastic leukemia (ALL), which may be common clinical manifestations or co-occurrence hematological diseases of patients with SLE. All these findings suggest that IKZF1 may play a critical role in the pathogenesis of SLE. In this article, we discuss the existing understanding of the role of IKZF1 on the physiological and pathological functions associated with SLE, providing insights that may assist in the development of new therapeutic strategies based on IKZF1 for patients with SLE.

Reversible phosphorylation of proteins is a key event in many fundamental cellular processes. Under stressful conditions, many thylakoid membrane proteins in photosynthetic apparatus of higher plants undergo rapid phosphorylation and dephosphorylation in response to environmental changes. CP29 is the most frequently phosphorylated protein among three minor antennae complexes in higher plants. CP29 phosphorylation in dicotyledons has been known for several decades and is well characterized. However, CP29 phosphorylation in monocotyledons is less studied and appears to have a different phosphorylation pattern. In this review, we discuss recent advancements in CP29 phosphorylation and dephosphorylation studies and its physiological significance under environmental stresses in higher plants, especially in the monocotyledonous crops. Physiologically, the phosphorylation of CP29 is likely to be a prerequisite for state transitions and the disassembly of photosystem II supercomplexes, but not involved in non-photochemical quenching (NPQ). CP29 is phosphorylated in monocots exposed to environmental cues, with its subsequent lateral migration from grana stacks to stroma lamellae. However, neither CP29 phosphorylation nor its lateral migration occurs in dicotyledonous plants after drought, cold, or salt stress. Since the molecular mechanisms of differential CP29 phosphorylation under stresses are not fully understood, this review provides insights for future studies regarding the physiological function of CP29 reversible phosphorylation.

The aims of this study were to explore the dose-response relationship between high-risk human papillomavirus (hrHPV) load and cervical lesions; the relationship between hrHPV viral load and the severity of cervical lesions; and the clinical application of the hybrid capture II (HC-II) system in the secondary prevention of cervical cancer. HrHPV viral load was detected by the HC-II system and cervical lesions were diagnosed from biopsied tissue. Curve estimation and Mantel trend analysis were used to explore the dose-response relationship between hrHPV viral load and cervical lesions. Spearman's rank correlation analysis and ordinal regression model were used for the analysis of hrHPV viral load and the severity of cervical lesions. Curve estimation showed good correlation between cervical lesion rates and hrHPV viral load (r=0.775, P=0.008); the rate of cervical lesions increased with hrHPV viral load (chi(trend)=8.000, P<0.001). Medium intensity rank correlation was found between hrHPV viral load grades and the severity of cervical lesions (r(s)=0.321, P<0.001); a correlation appeared between hrHPV viral load and the severity of cervical lesions (P<0.001). These results suggest a dose-response relationship between hrHPV viral load and the severity of cervical lesions. This dependence has important clinical applications and shows the potential value of the HC-II system in cervical cancer prevention.

Background: Tumour ablation using a thermal energy source has shown promising results, and is particularly suitable for recurrent hepatocellular carcinoma (HCC). The present study evaluated long-term outcomes after percutaneous thermal ablation for recurrent HCC following liver resection., Methods: Radiofrequency ablation or microwave ablation was used to treat a total of 124 tumour nodules (0.9-7.0 cm in diameter) in 72 patients with recurrent HCC., Results: Complete ablation of 119 (96.0 per cent) of 124 tumour nodules was achieved. There was no treatment-related death and the major complication rate was 4 per cent. During a mean(s.d.) follow-up of 27.9(17.8) months, local recurrence developed in 16 (13.6 per cent) of 118 successfully treated tumour nodules. Distant recurrence developed in 60 (85 per cent) of 71 patients, of whom 26 had repeat metachronous distant recurrence. With repeated ablation for both local and distant recurrence, the 1-, 3- and 5-year overall survival rates after initial ablation were 75, 43 and 18 per cent respectively. Patients with a serum alpha-fetoprotein level greater than 200 ng/ml before treatment had significantly poorer survival than those with a lower level (P = 0.034) and multivariate analysis identified preablation AFP level as an independent prognostic factor (P = 0.054)., Conclusion: With their advantages of preservation of non-tumorous liver tissue and easy repetition, percutaneous thermal ablative therapies were particularly suitable for recurrent HCC and improved long-term survival.

Background: Hepatic blood inflow occlusion during hepatectomy may influence postoperative liver regeneration. The aim of this study was to investigate the influence of hepatic blood inflow occlusion on liver regeneration following partial hepatectomy in thioacetamide-induced cirrhotic rats., Methods: Forty-three cirrhotic Wistar-Furth rats were randomly assigned to three groups. Rats in group 1 underwent 64 per cent hepatectomy alone, those in group 2 were subjected to 15 min hepatic blood inflow occlusion followed by 64 per cent hepatectomy, and animals in group 3 were subjected to 30 min inflow occlusion followed by 64 per cent hepatectomy. Liver function, 5-bromo-2'-deoxyuridine (BrdU) labelling index and percentage of initial liver weight on days 1, 2 and 7 posthepatectomy were assessed., Results: Rats in groups 1 and 2 had a significantly higher serum albumin level and a markedly lower alanine aminotransferase level than animals in group 3 on day 1 posthepatectomy (P < 0.05). There was no significant difference in the serum level of total bilirubin of the three groups on days 1, 2 and 7. The BrdU labelling index was significantly higher in groups 1 and 2 than in group 3 animals on day 1 posthepatectomy (P < 0.01 and P < 0.05 respectively). Percentages of initial liver weight were similar in groups 1, 2 and 3 on days 1, 2 and 7 after hepatectomy., Conclusion: Hepatic blood inflow occlusion for up to 30 min suppressed DNA synthesis and hepatocyte proliferation at an early posthepatectomy stage and consequently delayed recovery of liver function in cirrhotic rats. However, it did not affect restoration of liver mass or survival after 64 per cent hepatectomy.