Because the total gene copy number remains constant and all genes are normally expressed, carriers of balanced chromosomal translocations usually have a normal phenotype but are able to produce many different types of gametes during meiosis, and unbalanced gametes lead to increased risks of infertility, recurrent spontaneous abortion, stillbirth, neonatal death or malformations and intellectual abnormalities in offspring. The key to balanced translocations lies in finding the breakpoints, but current genetic testing techniques are all short-read sequencing, with the disadvantage of procedural complexity and imprecision for precisely identifying the breakpoints. The latest third-generation sequencing technology overcomes these drawbacks and uses robust long-read sequencing to accurately and rapidly detect genome-wide information and identify breakpoint locations. In this paper, we performed whole genome long-read sequencing using an Oxford Nanopore sequencer to detect the breakpoints of 4 balanced chromosomal translocation carriers. The results showed that employing about ~ 10× coverage confirmed 6 of the 8 breakpoints, of which, 2 had microdeletions/insertions identified near the breakpoints and 4 had breakpoints that disrupted the normal gene structure and were simultaneously tested for genome-wide structural variation (SV). The results show that whole genome long-read sequencing is an efficient method for pinpointing translocation breakpoints and providing genome-wide information, which is essential for medical genetics and preimplantation genetic testing. Chromosomally balanced translocation carriers usually have a normal phenotype because the total gene copy number remains constant and all genes are normally expressed. However, in a few cases, translocations have been reported to be associated with various diseases4. It can produce at least 18 different types of gametes during meiosis, of which only one type is normal, one type is balanced, and the rest carry unbalanced chromosomal changes, which are derivatives of terminal sequence duplications and deletions on either side of the breakpoint6. Fertilization of unbalanced gametes may lead to infertility, recurrent spontaneous abortions, stillbirths, neonatal death or malformations and intellectual abnormalities in offspring. Fertilization reproduction of normal/balanced gametes depends on the chromosome involved, breakpoint location, segregation pattern, and sex of the translocation carrier8, with approximately 1/500 to 1/1000 live births being balanced translocation carriers9. The ability to identify fully normal embryos through the precise localization of balanced translocation breakpoints may prevent future generations from facing the same reproductive dilemma. Breakpoints are a common phenomenon that occurs during chromosomal recombination during meiosis and can lead to genetic variation, and patients with pathogenic translocations usually have breakpoints within or near disease genes10.Structural variation (SV) is usually defined as a region of DNA that changes in copy number , orientation (inversions), or chromosomal position (translocations) between individuals. SV can be balanced, with no loss or gain of genetic material, such as inversions of genetic segments or translocations of intra- or interchromosomal DNA segments, or unbalanced, in which a portion of the genome is lost or duplicated , called copy number variation (CNV)11, at which point the best strategy is to select only euploid non carrying balanced translocated embryos. Even more so, the difficulty of obtaining normal/balanced embryos is increased by the presence of balanced translocations in both partners, which have been reported in several cases of consanguineous marriages in which offspring underwent pregnancy termination due to different phenotypic abnormalities15. Preimplantation genetic diagnosis (PGD) enables embryo biopsy of chromosomal translocation carriers to select normal or balanced euploid embryos for intrauterine transfer, which will effectively reduce miscarriage and improve live birth rates16.In some special balanced translocation carriers such as: when the reciprocal translocation involves the X chromosome, the phenotype of balanced carriers is unpredictable due to random inactivation of the X chromosome during early embryonic development20. However, translocation breakpoints are often associated with highly repetitive sequences, and determining precise breakpoints in highly repetitive and variable translocation regions remains unstable and inaccurate21. At present, the inadequate sequencing accuracy and short fragment length are still the shortcomings of short-read sequencing that cannot be ignored. Third generation sequencing addresses these issues, and the long read lengths (> 10 kb on average) it produces will greatly improve SV detection, finding translocation breakpoints regardless of whether the SV is located in a repetitive region and can cover up to two million bases up—and downstream of the breakpoint. Two technologies are currently available: single molecule real-time sequencing (SMRT) by Pacific Biosciences and Oxford Nanopore sequencing (ONT) by Oxford Nanopore technologies.Both allow sequencing of non amplified native DNA with ultra long linear read lengths (1–100 kb/s) and rapid sequencing times (2–10 h)23. The use of third-generation sequencing for structural chromosomal rearrangements, gene fusions and deletions or insertions involving DNA bases has been described, with fewer reports for preimplantation genetic testing (PGT) applications26. In this study, we resequenced couples with reciprocal balanced translocations of known chromosomal status who were either carriers of chromosomal balanced translocations or patients with recurrent implantation failure, explored the use of third-generation sequencing for higher sequencing depth, analysis of longer genomic fragments, and further analysis of structural rearrangement details in couples with balanced translocations to provide more accurate genetic information for PGT.Various methods are currently available for breakpoint identification, such as single nucleotide polymorphism (SNP) array, microdissection, next-generation sequencing, allele mapping identification, paired end sequencing by haplotype linkage analysis (PGH)6/ml, total motility 7.9%, normal morphology 3%), suggested by karyotype analysis: 46, XY, t. There was no consanguinity in either side. Assisted reproduction assisted pregnancy was performed with PGD by array comparative genomic hybridization (aCGH) technique and transfer of a balanced/normal D5 frozen embryo prompted by amniocentesis at 19 + weeks: 46, XN, t pat.Case 1: a young couple, wife 29 years, husband 30 years, with 5 years of infertility. The wife's karyotype analysis prompted: 46, XX, t; The husband's semen was examined for Oligozoospermia ; The husband's karyotype was normal: 46, XY. All four cycles of assisted reproduction failed to achieve pregnancy, none of the three cycles of artificial insemination with husband's sperm (AIH) were implanted, and one cycle of in vitro fertilization (IVF) cancelled PGD due to no good quality blastocysts.Case 3: The wife is 26 years old and the husband is 26 years old, with 3 years of infertility. The wife's karyotype was normal: 46, XX; the husband's karyotype analysis was suggestive: 46, XY, t. Two cycles of IVF assisted pregnancies failed, four good quality blastocysts were obtained in the first cycle, one D5 balanced/normal embryo was obtained by PGD biopsy, one D6 good quality blastocyst was obtained by ET and one euploid unbalanced embryo was retrieved by MaReCs PGD.Blood samples were taken to freshly extract DNA, which was forbidden from freezing. High quality genomic DNA was isolated from each sample using the SDS method. DNA quality and concentration were tested by 0.75% agarose gel electrophoresis, nanodrop one spectrophotometer (Thermo Fisher Scientific) and qubit 3.0 fluorometer .The ONT ligation sequencing protocol LSK109 was chosen to construct the sequencing library and the prepared library was loaded onto the R9 chip for 1D sequencing, the library preparation process took 1h30min. The following is the procedure: Genomic DNA was sheared into fragments of approximately 5–25 kilobases using meagruptor 2  followed by size selection (10–30 kilobases) with the bluepippin apparatus  to remove small DNA fragments. Sheared deoxyribonucleic acid was end repaired using the NEBNext Ultra II End-Repair/dA-tailing Module and then end repaired with (1×) Ampure beads for purification. This module repairs fragmented DNA to produce DNA with 5′ phosphorylation and 3 ′ ends. The end repaired DNA was incubated with NEB blunt/TA mix  using (0.6×) Ampure beads  elution, repaired DNA was used for adapter ligation, purified products were sequenced adapter ligation using the SQKLSK109 ligation kit, cleaned end repaired DNA was quantified using the Qubit dsDNA assay kit, and purified libraries were loaded onto starting R9.4 Spot-On flow cells and sequenced using a PromethION sequencer  running for 48 h at Wuhan benagen tech solutions company limited, Wuhan, China.The raw data were subjected to base calling analysis using Oxford Nanopore GUPPY software (v0.3.0). Raw sequencing data were in FAST5 format and first converted to FASTQ format using the MINKNOW base caller. Structural variants were then called using a workflow combining Minimap2 and NanoVar, an optimized structural variant caller that utilizes the low depth (~ 10× coverage) generated by Oxford Nanopore Technology whole genome sequencing data. Briefly, long reads were aligned to the human reference genome (GRCh37) using minimap2 (version 2.17-r941) with "—ax map ont – MD " parameters, followed by SV calling performed by NanoVar with default parameters. To maximize the sensitivity of translocation discovery, all split reads mapping to different chromosomes were collected and their detailed mapping information was recorded using custom Perl scripts. As a quality check, the integrative genomics viewer (IGV) was used to manually inspect the translocations detected in the targeted regions. Removal of sequences with average mass value less than or equal to 7.The studies involving human participants were reviewed and approved by ethics committee of Fujian Provincial Maternal and Child Health Hospital. All couples received detailed genetic counseling before receiving PGD, and were informed of the risks associated with reciprocal translocation carriers, the advantages and disadvantages associated with the PGD process, and the advantages and disadvantages of third-generation sequencing technology. The patients/participants provided their written informed consent to participate in this study. The research, including human subjects, human data and material, has been performed in accordance with the Declaration of Helsinki.GRCh37/hg19) and breakpoint positions are indicated in IGV  no breakpoint sequence information was obtained.We found six breakpoints in three samples in cases 1 and 2. The locations of the breakpoints were consistent with the karyotyping results.The balanced translocation carrier sequencing results DNA fragments were compared to the reference human genome  translocation carrier breakpoint in case 1 has 8 reads in IGV locating the position at chr3:170290668–170290678 and chrX:2653403–2657362, whose detection results show a 4 kb deletion at the breakpoint. 8 reads in the 46, XY, t translocation carrier breakpoint localized the position to chr13: 111045080–111045082 and chr16: 46392636–46398439/46404543, whose detection results showed a 6/12 kb deletion at the breakpoint. The 46, XX, t translocation carrier breakpoint in case 2 had 7 reads mapping in IGV to chr1:90951892–90951904 and chr3:65495358–65495367.COL4A2 gene by the translocation carrier 46, XY, t chromosome 13 breakpoint in case 1, which encodes a protein important for angiogenesis and tumor growth suppressors, and the chromosome 16 breakpoint does not involve a functional gene. Translocation carriers with a 46, XX, t chromosome 3 breakpoint disrupting the CLDN11, SLC7A14, BC039437 genes encoding proteins that are important components of the central nervous system.SLC7A14 associated with recessive disease, and BCO039437 that function similarly to CLDN11 encoded proteins. The X chromosome breakpoint disrupts the CD99 gene structure, which is associated with a variety of malignant neoplastic diseases, and the gene breakpoint occurs in an AluSc element. The chromosome 3 breakpoint in the translocation carrier 46, XX, t in case 2 disrupts the MAG11 gene, but no pathogenicity has been reported for this gene so far and no functional gene has been implicated in chromosome 1. These breakpoints disrupt the gene structure, leading to the exchange of chromosomal segments, as a portion of the gene on one chromosome is transferred to the other chromosome, thereby impairing gene function. However, with the exception of primary infertility, there was no apparent effect on the phenotype of the carriers from whom the sample was obtained.Inspection of these breakpoints in the UCSC Genome Browser Table ; Fig. 2 CD99 B.chr3: CLDN11, SLC7A14, BC039437 C.chr13: COL4A2 D.chr3: MAG11.Diagram of breakpoints aligned to the reference genome in UCSC(the area in the red box is the breakpoint disruption gene): A.chrX: Whole genome testing was performed on the samples, and the results of SV testing are shown in Fig. 27. NGS technology enabled high-resolution and high-throughput analysis with comprehensive chromosome screening (CCS) of all 24 chromosomes by using aCGH or next-generation sequencing (NGS). Multiple clinical trials have shown that the use of CCS increases pregnancy and live birth rates per transfer cycle29. But NGS creates difficulties due to defects in their read lengths (35–600 bp) when breakpoints are located in complex repeat regions with low mapping rates, making it difficult to accurately detect their location. In identifying translocation breakpoints by long-range pairing, Hu et al. used laser microdissection to identify SNP markers associated with the translocation associated allele10. It is a NGS based CCS approach to address the translocation carrier status of embryos, and while this approach can identify translocation affected alleles, it requires highly specialized equipment and complex sample preparation procedures, making it unlikely to be available for routine clinical use30. A SNP array based linkage analysis approach was also used to identify translocation free embryos. However, it has limited accuracy in breakpoint identification and linkage analysis31. MALBAC-NGS can increase the accuracy of breakpoint determination to 200 kbp, reducing the current range limit for informative SNPs to 1Mbp on either side of the breakpoint. MaReCs are a reliable method to distinguish the translocation carrier status of embryos from balanced translocation carriers. It can help a proportion of balanced translocation carriers select completely normal embryos, while reducing the transfer of embryos carrying balanced translocations, with the limitation that it requires the availability of reference embryos21.Currently, karyotyping is the most widely used technique for clinical diagnosis of chromosomal translocations, however, it is a low resolution method that can only find the breakpoints at the chromosomal level and cannot determine the exact breakpoints. FISH is limited to the detection of very few chromosomes and since it relies on fluorescent labelling, the results are sometimes inconclusive due to ambiguous optical signals and complex sample preparation procedures32. Nanopore sequencing is a single-molecule long read sequencing technology that overcomes the limitations of short read sequencing, such as the inability to reliably resolve repetitive sequences or large genomic rearrangements, typified by long reads (> 1 kb to 2 Mb) and real-time sequencing. Compared with other platforms, Nanopore sequencing has many potential advantages, including the possibility of label free sequence determination of native DNA and RNA molecules without amplification and the ability to generate extremely long read lengths, with some groups reporting read lengths > 2 Mb18. This greatly increases the chance of obtaining chimeric reads overlapping breakpoint junctions.In this paper we successfully identified and sequenced each breakpoint in three cases of balanced translocation carriers by long-read sequencing, and all six breakpoints were consistent with their corresponding karyotype results. Many previously unidentified minor structural variants were found at two breakpoints (translocation chromosomes 8 and 16). These results suggest that certain copy number deletions are often detected near the breakpoints. Microdeletions/insertions often occur in conjunction with translocations, and mutual chromosome translocations are usually accompanied by some additional rearrangements, such as deletions and duplications, which can involve a few base pairs or up to millions of bases1. This analysis allowed us to perform statistics on SVs in our samples by contrasting them with reference genes, and since our study focused on translocations already identified by karyotype, we did not perform a more detailed analysis of SVs. But these data suggest that, on SV statistics, the adoption of long-read Nanopore sequencing is more likely to encompass entire structural variants and/or repetitive regions, leading to more accurate and precise structural variants and an improved understanding of structural variation and the role of structural variation in disease, evolution and genetic diversity.Genomic structural variants generally refer to large length sequence changes and positional relationships across the genome and are rich in variant types, including long segmental sequence insertions or deletions (big indel), tandem duplications, chromosomal inversions, chromosomal translocations, copy number variations (CNV), and more complex forms of mosaicism. Compared to SNPs (single nucleotide polymorphisms), SVs make up a larger proportion of the variant base, have a greater impact on the genome, and, once altered, tend to have a major impact on the body of life. In humans, such structural variants have been associated with many diseases ; On plants, SVs are associated with many phenotypic variations and thus become increasingly important research areas. Most high-throughput sequencing technologies basically sequence short pieces of DNA , which is more difficult and less accurate in analyzing larger structural variations33. For samples that test negative if testing is to be continued to find the break points can increase the Nanopore sequencing depth, as indicated by the 10× coverage was increased to 20× or 30× coverage.Greatly improve the probability of breakpoint detection. But the detection will cost quite a bit more. The site of the balanced translocation is mapped with high accuracy by mate-pair, this particular next-generation sequencing can generally be mapped to the 1–10 k interval, and then the mapped interval is examined by high depth next-generation sequencing or direct Sanger sequencing to find the precise break site.The major drawbacks of the third-generation sequencing platform are the lower throughput and higher error rate, there was one failure case in this paper, the breakpoint position information was not detected, which would lead to two impacts due to the high cost and single base error rate of third generation sequencing, first, the cost of sequencing limits the sequencing depth, and the average sequencing of whole genome is 10× coverage.But not completely average, and some will be above 10× coverage, some locations below 10× coverage even less well covered. It is possible that the sequencing depth at the breakpoints of balanced translocations is too low to result in difficult detection; The second is the high Nanopore single base error rate, which, if at a relatively low sequencing depth, may lead to difficulties in information analysis, i. e. increasing the difficulty of aligning sequencing reads back to the reference genome. It is possible that there was genomic information at the breakpoints measured at the time of sequencing, but this was not detected due to alignment errors resulting from sequencing errors. But with the release of the platform and advances in flow cell design and sequencing chemistry, error rates as low as 3% can now be achieved32. In a study reported by Chun et al. using Nanopore sequencing in a newly diagnosed AML patient, conventional karyotyping showed translocation t but RNA NGS detected NUP98-NSD1 fusion transcripts from a known cryptic translocation t. Rapid PCR-free Nanopore whole-genome sequencing yielded a 26,194 bp sequencing read and revealed the t breakpoint to be DUSP13 and GRIN2B in head-to-head configuration. This translocation was then classified as a passenger structural variant. The sequencing also yielded a 20,709 bp sequencing read and revealed the t breakpoint of the driver NUP98-NSD1 fusion. The identified DNA breakpoints also served as markers for molecular monitoring, in addition to fusion transcript expression by digital PCR and sequence mutations by NGS. This suggests that third-generation Nanopore sequencing is a simple and cost-effective workflow for DNA translocation detection34.Third generation sequencing holds great promise. The main applications of Pacbio sequencing include WGS, targeted sequencing, full-length mRNA sequencing, sequencing of complex populations, and detection of epigenetic modificationsThird generation sequencing technology can directly obtain genomic sequence information and simultaneously perform SV detection by performing long read sequencing, and has significant advantages in detecting gene minor variations, and can accurately identify translocation breakpoint position information for carriers of chromosomal balanced translocations, making genomic information more refined and extensive, which can provide accurate and rich genetic information for PGT. However, the technique is still more expensive to analyze, and the occurrence of experimental failure still needs further increased sample in-depth study.


We designed a functional recovery analysis by using semantic visualization to predict the recovery probability in AIS patients receiving intravenous thrombolysis; (2) Methods: We enrolled 131 AIS patients undergoing intravenous thrombolysis from 2011 to 2015 at the Medical Center in northern Taiwan. An additional 54 AIS patients were enrolled from another community hospital. A modified Rankin Score ≤2 after 3 months of follow-up was defined as favorable recovery. We used multivariable logistic regression with forward selection to construct a nomogram; (3) Results: The model included age and the National Institutes of Health Stroke Scale (NIHSS) score as immediate pretreatment parameters. A 5.23% increase in the functional recovery probability occurred for every 1-year reduction in age, and a 13.57% increase in the functional recovery probability occurred for every NIHSS score reduction. The sensitivity, specificity, and accuracy of the model in the validation dataset were 71.79%, 86.67%, and 75.93%, respectively, and the area under the receiver operating characteristic curve (AUC) was 0.867; (4) Conclusions: Semantic visualization-based functional recovery prediction models may help physicians assess the recovery probability before patients undergo emergency intravenous thrombolysis. In general, approximately 80% of all cerebrovascular disease cases are ischemic strokes. The subsequent management of sequelae after acute ischemic stroke (AIS) is associated with both higher medical expenses and time-consuming physical therapy. Intravenous thrombolysis can increase the survival rate and reduce disability or the length of hospital stay in patients with AIS ,2,3. SinA younger age and a lower National Institutes of Health Stroke Scale (NIHSS) score are associated with a better level of recovery . The DRANomograms are widely used for disease prognosis and support simple numerical estimated event probability. The nomogram algorithm is built based on statistically significant factors, and physicians can use the one-page nomogram to predict disease outcomes ,10,11,12Although endovascular treatment for large vessel occlusion has been increasingly performed in recent years , the tecIn this study, we collected retrospective data from 131 AIS patients who received intravenous thrombolysis treatment without contraindications within 3 h of stroke symptom onset from 1 January 2011 to 31 December 2015, in the Tri-Service General Hospital according to the Taiwan Stroke Association guidelines  contraindications). The validation dataset was collected by an emergency physician (C-G Cheng) from patients enrolled during the same period in Taoyuan Armed Forces General Hospital. The flowchart of this study is shown in The variables that were collected included age, NIHSS score measured in the emergency room within 3 h, sex, onset of treatment time (OTT), estimated glomerular filtration rate (estimated GFR), internal carotid artery occlusion, hypertension (blood pressure more than 140/90 mmHg or previously received antihypertensive therapy), diabetes mellitus (fasting blood sugar more than 126 mg/dL at two readings or previously received antihyperglycemic agents), previous stroke, coronary artery disease, atrial fibrillation, anemia , and dense middle cerebral arterial sign. Intracranial hemorrhage and stroke type  were noted after hospitalization. We adopted the mRS to evaluate the stroke recovery situation; an mRS ≤ 2 without significant disability in outpatients within 3 months after intravenous thrombolysis treatment was defined as favorable functional recovery.2) test, and the NIHSS scores were evaluated with the Mann–Whitney U test because this variable is not normally distributed for comparisons between two groups. A p-value less than 0.05 was considered significant. The predictors of functional recovery were assessed by multivariable logistic regression with forward stepwise selection with p < 0.05. The effect size is 0.3883 with NIHSS. The effect size was 0.4983 with NIHSS and ‘Age’. When we added diabetes mellitus with NIHSS and age, the effect size was 0.5067; however, the p-value of diabetes mellitus is 0.266, so it needed to be removed. When we added NIHSS, age, diabetes mellitus, and middle cerebral artery sign, the effect size was 0.5339; however, the p-value of diabetes mellitus is 0.244, and the p-value of middle cerebral artery sign is 0.105, so both diabetes mellitus and middle cerebral artery sign needed to be removed.The data are presented as the mean ± standard deviation (SD) or as a percentage. Continuous variables were evaluated with Student’s t test, categorical variables were evaluated with the chi-square  curve was constructed based on the sensitivity and false positive rate (1 − specificity). The area under the ROC curve (AUC-ROC) was used to evaluate the performance of the model, with an AUC-ROC of 0.7 considered good, 0.8 considered better, and 0.9 considered perfect performance. All statistical analyses were performed using R software version 4.0.5. An internal bootstrap validation for 200 resamples was performed to correct the overfitting bias of testing on the same patient population and to discriminate the functional recovery of two patients (overfitting-corrected concordance index [c-index] for discrimination) ,17.The training dataset consisted of 131 AIS patients with 78 males and 53 females; the mean age was 63.64 ± 12.1 years, the median NIHSS score was 15 with a range of 7–27, and 65 patients (49.62%) had a favorable recovery. The patients with a good recovery status were younger and had lower NIHSS scores, earlier onset treatment times, lower estimated glomerular filtration rates, a more lacunar or embolic infarction type, and less atrial fibrillation. The demographic characteristics of the training dataset are shown in We used data from another community hospital to validate our development model. The validation dataset included 54 AIS patients consisting of 26 males and 28 females; the mean age was 63.74 ± 10.12 years, the median NIHSS score was 12 with a range of 4–26, and 39 patients (72%) had a favorable recovery. No significant differences were found in age, sex, or the survival state between the training and validation datasets, but the median NIHSS score was lower and the functional recovery proportion was higher in the validation dataset . An older age, greater overall neurological impairment based on the NIHSS score, less lacunar ischemic stroke type, diabetes mellitus, and a dense middle cerebral arterial sign were associated with unfavorable functional recovery in the univariate analysis. In the multivariable logistic regression analysis, the independent predictive factors of functional recovery within 3 months after intravenous thrombolysis were age and NIHSS score. The recovery probability was increased by 5.23% for every 1-year reduction in age and 13.57% for every reduction in the NIHSS score . The senThe nomogram for semantic visualization was developed based on a multivariable logistic regression model. Age and the NIHSS score were the linear predictors used to calculate the functional recovery probability within 3 months after AIS. This prediction was determined by comparing the ‘age’ axis to the ‘points’ scale and by drawing a vertical line upward between the two axes; the same process was repeated for the ‘NIHSS’ factor. Summing the ‘Age’ and ‘NIHSS’ points gives rise to the ‘Total Points’ scale, and a vertical line drawn to the ‘functional recovery probability’ axis indicates the estimated functional recovery probability A. For exThis section may be divided by subheadings. It should provide a concise and precise description of the experimental results and their interpretation, as well as the experimental conclusions that can be drawn. The score distribution in both event and no-event groups in the training and validation cohorts is shown in The decision to undergo intravenous thrombolysis therapy requires rapid making, which causes anxiety and worry for patients and relatives regarding the outcome of the therapy. In this study, we used age and the NIHSS score before intravenous thrombolysis to develop a prediction nomogram as semantic visualization based on a medical center hospital dataset; then, the nomogram was externally validated using a community hospital dataset with good performance.p < 0.001), which was classified as poor recovery.A study in England found increased intracranial hemorrhage and mortality in patients admitted to the emergency department by ambulance; indeed, the urgent care of AIS patients is a challenging task . Female Using the DRAGON score with 6 categorical variables , a score of 0 predicts a good outcome (mRS: 0–2), and a score of 10 predicts a poor outcome (mRS: 5–6); therefore, in this scoring system, a lower score indicates a better prognosis (7). The iScore predicts the effectiveness of thrombolysis for AIS patients using a complex calculation method . Age (A)Our study explored different scores with different probabilities of functional recovery. A previous study in Japan found that a younger age, lower initial NIHSS score, absence of internal cranial artery occlusion, higher ASPECTS on CT, and absence of intravenous antihypertensive agents before intravenous thrombolysis were associated with good recovery at 3 months with low-dose intravenous thrombolysis treatment . Our stup = 0.5). Previous studies have found that atrial fibrillation is related to age in patients with sepsis and chronic obstructive pulmonary disease [p ≤ 0.001), and older patients with AIS had more atrial fibrillation reducing the influence of unfavorable functional recovery. The preventive treatment of embolic stroke with atrial fibrillation with anticoagulation therapy has educated physicians on stroke treatment and reduced recurrent stroke in recent years. The type of lacunar infarction in patients with AIS has better recovery [The crude OR of atrial fibrillation was 0.5079 (95% C.I.: 0.2311 to 1.1164), which seems to explore the trend of poor outcome with intravenous thrombolysis, but showed an insignificant difference. In addition, multivariable logistic regression with forward selection excluded atrial fibrillation. The logistic regression with added atrial fibrillation was no better than age and NIHSS  that may have been overestimated. A prospective study must include more severe AIS patients to validate this nomogram in the future. In addition, although pulmonary embolism or mechanical ventilation used after intravenous thrombolysis may affect recovery, our study focused on recovery prediction from the factors of patients in the emergency department.This study used a nomogram as semantic visualization for functional recovery prediction and included external validation in a community hospital. This study provided an applicable prognostic model with good performance for the prediction of the 3-month functional recovery after intravenous thrombolysis for individual patients in Taiwan based on age and the NIHSS score within 3 h of stroke onset but prior to treatment. Risks and benefits should always be balanced before any treatment is applied. Individualized recovery probability prediction can help stroke treatment physicians inform and discuss treatment options with patients and their families to reduce their anxiety about the outcome of treatment. During the hyperacute phase of ischemic stroke, intravenous thrombolysis may be recommended if the patient is predicted to have a favorable response, whereas a mechanical thrombus removal in large vessel occlusion may be considered for patients who are predicted to have poor recovery based on the nomogram as semantic visualization.This section is not mandatory but may be added if there are patents resulting from the work reported in this manuscript.


PTEN). It is associated with an increased risk of muco-cutaneous features, hamartomatous tumors, and cancers. Mosaicism has been found in a few cases of patients with de novo PHTS, identified from blood samples. We report a PHTS patient with no variant identified from blood sample. Constitutional PTEN mosaicism was detected through sequencing of DNA from different tumoral and non-tumoral samples.PTEN hamartoma syndrome (PHTS) is an autosomal dominant disorder characterized by pathogenic variants in the tumor suppressor gene phosphatase and tensin homolog  and non-tumoral stomach tissues found the same PTEN pathogenic variant ), with an allelic frequency of 12 to 59%, confirming genomic mosaicism for Cowden syndrome.Our patient presented clinical Cowden syndrome at 56 years of age, with three major criteria , and two minor criteria . Deep sequencing of PTEN hamartoma syndrome in the absence of any causal variant identified in blood leukocytes, despite deep sequencing. In 65 to 70% of cases of clinical Cowden syndrome, no pathogenic variant in the PTEN is observed in blood samples: mosaicism may explain a significant number of these patients. Tumor analysis would improve our knowledge of the frequency of de novo variations in this syndrome. Finally, patients with mosaicism for PTEN may not have a mild phenotype; medical care identical to that of heterozygous carriers should be offered.This case report, and review of the literature, suggests that systematic tumor analysis is essential for patients presenting  PTEN) [PTEN hamartoma syndrome (PHTS) is an autosomal dominant disorder characterized by pathogenic variants in the tumor suppressor gene phosphatase and tensin homolog (PTEN) . The cliPTEN) , BannayaPTEN) , LhermitPTEN) , SegmentPTEN) , and autPTEN) .The prevalence of CS, probably underestimated, is estimated at 1 in 200,000 individuals , with a Mosaicism has been found in a few cases of patients with de novo PHTS . This moPTEN through deep sequencing of DNA from blood samples. Constitutional PTEN mosaicism was detected through sequencing of DNA from different tumoral and non-tumoral tissues. We review PHTS mosaicism reported in the literature, and suggest that mosaicism be actively searched for when possible.We present a patient with clinical CS, with no identified pathogenic variation in A 56-year-old man presented left-sided hyperacusis and loss of ipsilateral stapedial reflex. A cerebral MRI was performed and identified an infiltrative mass 57 mm in diameter located in the left cerebellar hemisphere, without enhancement of the contrast product, suggestive of a hamartomatous lesion of the posterior fossa.Given the absence of symptoms, in particular of intracranial hypertension on ophthalmological examination, a control MRI was performed 3 months later. This second MRI found a characteristic appearance of Lhermitte Duclos disease (dysplastic gangliocytoma) of the left cerebellar hemisphere, with a striated lamellar appearance, measuring 60 mm × 36 mm × 31 mm. This lesion was associated with a mass effect on the lower part of the fourth ventricle, resulting in moderate triventricular hydrocephalus (Evans Index at 0.35), with slight signs of transpedicular cerebrospinal fluid (CSF) resorption.The patient’s medical records did not report any delay in psychomotor development or learning difficulties. He had a history of “diapneusia fibroids” of the tongue that had been treated surgically some years earlier, and high blood pressure which was well-controlled by a combination of Angiotensin II antagonist and calcium channel blocker. The clinical examination found macrocephaly, with a head circumference of 60 cm (+ 2SD). Cutaneous-mucosal examination identified seborrheic keratosis in the shoulders and in the extremities. It also found fibrous lesions in interdental positions 31–32 and 32–33, as well as on the right lateral edge of the tongue. No cutaneous trichilemmomas or papules were found.In this context, a check-up for other lesions was performed. Thyroid ultrasound found multinodular hypertrophy of the right lobe with five nodular and cystic lesions (3 to 15 mm in diameter), Eu-thirads 3. Esogastroduodenal fibroscopy found oesophageal papillomatosis, confirmed histologically, and hyperplastic polyps of the gastric antrum. Colonoscopy identified a 6-mm-diameter ganglioneuroma of the transverse colon, confirmed histologically.The patient’s family history was not suggestive of PHTS, with no notable history. A clinical diagnosis of CS was made, due to the presence of three major criteria: Lhermitte Duclos disease in adult, macrocephaly, and oral papillomatosis. Two minor criteria were also present, including thyroid structural lesions and esophageal glycogenic acanthosis, as well as a unique digestive ganglioneruoma.PTEN gene (NM_000314.4) were performed.To confirm the clinical diagnosis, constitutional and tumor analyses of the 2, 6 mm2 and 2 mm2.DNA was extracted from peripheral blood using the QIAamp DNA Blood maxikit (Qiagen) and from oesophageal papilloma, ganglioneuroma, diapneusia fibroid and non-tumoral stomach tissue formalin-fixed paraffin-embedded blocks, using the Maxwell 16 FFPE Plus LEV kit (Promega). Libraries were prepared using KAPA HyperPlus Kits and captured using KAPA HyperCap Target Enrichment (Roche). The quality of libraries and captures was controlled with a Tapestation 4150 (Agilent). Sequencing was performed with a NextSeq 500/550 High Output Kit v2.5 (300 Cycles) on a NextSeq 550 instrument (Illumina). The percentage of tumor cells from the colon sample was 60%. The tumor surface of the esophageal sample, diapneusia fibroid and non-tumoral stomach tissue was respectively 16 mmDe-multiplexing was performed using bcl2fastq2 Conversion Software (Illumina). Alignment was performed on University of California Santa Cruz human genome reference build 19 using the Burrows-Wheeler Aligner (v0.7.17). Genome Analysis Toolkit (GATK v 4.1.8.0) and PICARD (v 2.22.8) tools were used for base quality score recalibration  and identified duplicate reads (MarkDuplicates). Variant calling was performed by GATK HaplotypeCaller and by GATK Mutect and Freebayes (v1.2.0). Annotations were added by Ensembl VariantEffectPredictor (v96.0) and Annovar (8 Jun 2020). Copy number variation analysis was performed using ExomeDepth (v 1.1.12).PTEN gene were analyzed in all samples . The entire 5'UTR and 3'UTR regions up to position *20 were analyzed from blood samples only. Due to the clinical presentation, no other gene was analyzed from all samples explored. Variants were filtered on mapping quality, call quality and minimum depth of coverage of 30 × for blood sample and 200 × for tumor samples. The detection threshold for constitutional analysis was 20% of reads. The detection threshold for tumor analyses was 10% of reads. The technical sensitivity was greater than 95%.The entire coding sequence and intron/exon junctions (positions up to -20 and + 6) of Variant interpretation was performed using ALAMUT Visual 2.11 (Interactive BioSoftware), and relevant databases (ClinVar). Splice variants were interpreted using SpliceAI (v1.3) and SPIP (v1.0) softwares. Variants were classified according to the American College of Medical Genetics (ACMG) recommendations.PTEN was 1633 with 100% coverage at 30X, 98.5% at 100X and 77.61% at 1000X. No constitutional variation of the PTEN gene was found from blood samples.NGS sequencing from two independent blood samples was first performed. The average depth for PTEN from the blood samples, two tumor samples were analyzed . The average depth was 3807 with 100% coverage. at 1000X and 95% at 1500X. The same pathogenic variant, c.389G > A; p.(Arg130Gln), was identified in both samples. The variant allele frequency was 12% in the ganglioneuroma sample (tumor cell content 60%) and 59% in the esophageal papilloma sample (tumor cell content unknown) . The same pathogenic variant was found with an allele frequency respectively at 25% and 14%, confirming the diagnosis.Given the strong clinical suspicion, and the absence of a probable pathogenic or pathogenic variant identified in PTEN hamartoma tumor syndrome.This variant is located in the phosphatase functional domain of the protein. It is a recurrent pathogenic variation, involved in different clinical presentations associated with In addition, an acquired unknown significant variant c.816C > G, p.(His272Gln) was found in ganglioneuroma and papilloma tumoral samples, with allelic frequency respectively at 11 and 8%., that included six patients, and three another cases were reported in the studies of Steffan et al. and Hendricks et al. [Mosaicism is very rare in PTHS and only a few cases have been published. Most of these were reported in the study of Rofes et al., that ins et al. –20 , in patients with PTHS criteria not carrying a causal pathogenic variant in PTEN, which is not the case in our study.Concerning the first hypothesis, various studies have identified candidate genes of interest, such as , PIK3CA , SEC23B  [SEC23B  or more 3B [WWP1 . AlthougPTEN mosaicism were diagnosed based on the analysis of blood samples. The classical Sanger technique is sensitive enough to find mosaicism with an allelic frequency of about 10%, which was enough to confirm the diagnosis in a number of cases [The second hypothesis depends on the samples analyzed and the analysis techniques. Most of the patients reported with constitutional of cases .PTEN variant at a frequency of 0.7% (17 / 2285 reads) which is below reasonable sensitivity in diagnostic practice. A similar patient, with a variant undetectable in the blood sample (VAF < 1%) but found in two other tissues , was reported by Hendricks et al. [However, for low-level mosaicisms, NGS and deep sequencing exploration is preferred and it is now performed routinely in many molecular genetics laboratories. The improved sensitivity allowed detection of variants at lower allele frequencies in two PHTS patients of the cohort (1.70% and 3.50% from lymphocytes). In our patient, NGS sequencing failed to detect a variant in DNA from blood, and tumor samples exploration was required. After the identification of the same variant in different tumors and healthy tissue, manual proofreading of the blood sequencing data revealed the causal s et al. .Deep sequencing (≥ 2000x) in the exploration of mosaicism in hereditary predisposition to cancer is of well-known interest and can detect single nucleotide variants at a frequency of 2–3% in blood samples . HoweverPTEN from blood sample does not rule out the diagnosis of PHTS, and the continued investigation of other tissues must be systematic in patients presenting the testing criteria. This is relevant in this syndrome, because multiple tumoral occurrences are very common. A non-tumor sample could also help to confirm the molecular diagnosis. This is what was done in our study, with the exploration of a non-tumoral stomach tissue sample, confirming the presence of the pathogenic variant PTEN outside any context of tumorogenesis, directing on its constitutional character. It should be noted that the cellular composition of buccal swab samples tends to be rich in leukocytes, and should not be considered a different that blood sample [Thus, the absence of a pathogenic variant in d sample .PTEN analysis, without identified causal variation. Systematic tumor analysis for these cases, as well as a cohort study, could better estimate the frequency of mosaicism in PHTS. The identification of these patients is important in clinical practice, for their medical management, as well as for that of their family.Mosaicism could explain some patients presenting diagnostic criteria for PTEN mosaicism does not seem to be associated with a milder phenotype, the clinical management of concerned patients, including genetic counselling and pre-natal testing, should be the same as that for people with a constitutional heterozygous variant, with the exception of parental testing, which is not useful in the context.Because PTEN mosaicism in a patient diagnosed through DNA sequencing from tumoral and non-tumoral tissue samples. This report highlights the interest of additional tissue analysis when peripheral blood sample DNA sequencing does not identify a causal variant. Based on a review of the literature, we propose that this analysis should now be systematic in this context in clinical practice. Moreover, the literature review provided in this report suggests that PTEN mosaicism is not associated with a milder phenotype of the syndrome. The personal and family care of these patients should be identical to that proposed to heterozygous carriers of PTEN, with the exception of testing of the parents.In conclusion, we report a case of


Infants who were less than 30 weeks of gestational age were included. After randomization, initial ventilator settings were adjusted for each patient. After the first 2 h of ventilation, the patients were switched to the other ventilator mode for 2 h. The ventilator parameters, vital signs, and blood gas values were evaluated. The study included a total of 28 patients, 14 in the PRVC group and 14 in the bilevel VG group. The mean birth weight was 876 g (range: 530–1170) and the mean gestational age was 26.4 weeks (range: 24–29). The patients’ peak inspiratory pressure (PIP2 and PIP3) was lower after ventilation in bilevel VG mode than in PRVC mode . After 2 h of bilevel VG ventilation, the mean heart rate decreased from 149/min to 140/min (p = 0.001) and the oxygen saturation increased from 91% to 94% (p = 0.01). Both the PRVC and bilevel VG modes of GE ventilators can be used safely in preterm infants, and bilevel VG mode was associated with more favorable early clinical findings. Studies including more patients and comparing with other modes will clarify and provide further evidence on this subject.The present study aimed to compare the bilevel volume guarantee (VG) and pressure-regulated volume control (PRVC) modes of the GE One of the most important steps in reducing neonatal morbidity is to prioritize noninvasive respiratory support and avoid invasive mechanical ventilation. However, the latter is used as rescue therapy in infants with severe respiratory distress. According to US Neonatal Research Network data for 2018, 84.3% of infants at <29 weeks of gestation received conventional mechanical ventilation support during their stay in the NICU [Rapid advances in ventilator technology have resulted in numerous basic and complex respiratory support modes. To understand how a mechanical ventilator works, one must be knowledgeable about the features of these specific modes, how they interact with an alert and spontaneously breathing infant, and mode definitions specific to the ventilator in the unit ,3.At present, tidal volume-targeted synchronized ventilation modes are most recommended for ventilating preterm infants. Tidal volume-targeted synchronized ventilation has been shown to provide shorter ventilatory support duration and lower rates of adverse effects such as pneumothorax, hypocarbia, severe intracranial hemorrhage, mortality, and bronchopulmonary dysplasia (BPD) ,5,6,7.T) [Along with the increase in available ventilator types and modes, ventilator modes have become more complex, and the parameters that were previously entered and adjusted by the clinician are now automatically adjusted by the device. Bilevel volume guarantee (VG) and pressure-regulated volume control (PRVC) modes are examples of this adaptive target scheme . In an aT) ,9.® Carescape R860 model ventilator and test the safety and feasibility of these two modes in preterm neonates.As experience and evidence regarding the use of new tidal volume-targeted devices and modes in neonatal intensive care units (NICUs) are limited, there is a need for safety and efficacy studies and comparative trials of these modes. The present study aimed to compare the bilevel VG and PRVC modes of the GEThis study was conducted in the NICU of Ankara City Hospital between January 2020 and June 2021, serving as a referral for tertiary care. This study was designed as a prospective, randomized crossover study. Infants who were less than 30 weeks of gestational age, required intubation and mechanical ventilation in the first 24 h of life, received surfactant at least once, and were clinically stable at postnatal 24 h were included in the study. Patients whose families did not provide consent, who had major congenital anomalies at admission, or who had congenital heart disease were excluded. Patients who met the selection criteria were randomized after the first surfactant administration to crossover ventilation with bilevel VG and PRVC for 2 h each using the sealed envelope method with grouping by weight. Group 1 (PRVC): Bilevel VG mode first, PRVC mode second, then continued with PRVCGroup 2 (bilevel VG): PRVC mode first, bilevel VG mode second, then continued with bilevel VG.In block randomization, weight stratification categories were determined as 500–750 g, 751–1000 g, and 1001–1250 g. As blinding was not possible due to the nature of the study, the sealed envelope method was used to help ensure balance and reduce bias. 2, positive end-expiratory pressure (PEEP), pressure support (PS), VT, respiratory rate, inspiratory time (Tins), inspiratory pressure minimum (Pmin) and maximum (Pmax). In bilevel VG mode, FiO2, VT, PEEP, respiratory rate, Tins, and Pmax were set. VT was set to 5 mL/kg and the target blood gas values were pH 7.25–7.35, PaCO2 45–55 mmHg, and PaO2 50–70 mmHg.After group assignment, the infants were monitored with the designated ventilation mode. The following ventilator parameters were set in PRVC mode: FiOT. All spontaneous efforts trigger pressure-assisted breaths. In SIMV PRVC mode, the ventilator delivers synchronized pressure-regulated, volume-controlled breaths at the set respiratory rate. For each mechanical breath, the ventilator adjusts the inspiration pressure to the lowest pressure needed to provide the target VThe ventilator provides volume-controlled ventilation for 10 s or two breaths (whichever is longer when the mode is initiated) to determine the patient’s lung compliance. Inspiratory pressure is determined according to lung compliance and used for subsequent breaths. 2O as the upper limit. The difference in inspiratory pressure between breaths does not exceed ±3 cmH2O. If a high airway pressure alarm is activated for the current breath, the target pressure for the next breath is reduced by 0.5 cmH2O.When adjusting inspiratory pressure, the ventilator uses PEEP + Pmin as the lower limit and Pmax—5 cmHT according to the set respiratory rate and Tins values. As in PRVC mode, the ventilator determines lung compliance by providing volume-controlled ventilation over 10 s or two breaths (whichever is longer when the mode is initiated) and this is used to determine inspiratory pressure for subsequent breaths. Inspiratory pressure limits and adjustments are also the same as in PRVC mode. In Bilevel VG mode, if the patient initiates a breath at the PEEP level, a pressure-supported breath is provided at the set PS. The ventilator switches between the PEEP and minimum pressure to maintain the target V®, Chicago, IL, USA, Carescape R860 model ventilator. After randomization, initial ventilator settings were adjusted for each patient and recorded as the starting point. Respiratory rate, heart rate, and pulse oximetry (SpO2 90–94%) values were continuously monitored in all patients. After the first 2 h of ventilation, the patients were switched to the other ventilator mode for 2 h. Ventilator parameters, vital signs, and blood gas values were evaluated at the beginning of the study, after the first ventilation mode, and after the second ventilation mode  data, or estimated postnatally using the New Ballard Score . Respira2 requirement > 40% received early rescue surfactant therapy. All patients in the study received surfactant  within the first 2 h of NICU admission and were monitored using GE®, Carescape R860 model ventilators. In accordance with unit protocols, surfactant therapy for RDS was administered prophylactically at NICU admission or as early rescue therapy in the first two hours according to the following criteria: as per the recommendations of the Turkish Neonatal Society, preterm infants at gestational age < 26 weeks that did not receive antenatal steroid therapy and preterm infants that required intubation in the delivery room received prophylactic surfactant; infants with signs of RDS findings and FiO2 requirement ≥ 60%, respiratory acidosis (pH < 7.2) under PEEP ≥ 7 cm H2O, and recurrent apnea.Noninvasive ventilation techniques and less invasive surfactant administration methods are encouraged in all patients with a good respiratory drive however patients were intubated and mechanically ventilated if they fulfilled the following criteria. Hypoxemia despite FiO2 ≥ 21;Mild BPD, nasal cannula oxygen < 2 L/min, FiO2 ≥ 21;Moderate BPD, nasal cannula oxygen > 2 L/min or nCPAP or NIPPV, FiO2 ≥ 21.Severe BPD, invasive PPV, FiOBPD in a preterm infant < 32 weeks of gestational age is defined as radiographically confirmed persistent parenchymal lung disease and is classified according to oxygen requirement at postmenstrual 36 weeks as follows ,15:Mild PDA refers to the nonclosure of the ductus arteriosus after the first 72 h of life. The diagnosis of hemodynamically significant PDA is made by demonstrating high-volume flow through the PDA on echocardiography. The first choice of medical treatment for PDA in our clinic is ibuprofen in two doses, 10 mg/kg/day followed by 5 mg/kg/day, administered 24 h apart .ROP screening is performed in all infants born at a gestational age of <34 weeks and a birth weight of <1700 g, as well as infants with a gestational age of ≥34 or a birth weight of >1700 g who received cardiopulmonary supportive treatment or is considered by the attending clinician to be at risk of ROP. The first ophthalmological examination is performed at postnatal 4 weeks. In our unit, the criteria specified by the multicenter ETROP (Early Treatment for Retinopathy of Prematurity) study group are used in the application of laser photocoagulation for ROP .Proven sepsis is defined as the presence of clinical and laboratory findings consistent with sepsis and a demonstrated causative pathogen. Clinical sepsis is defined as the presence of clinical and laboratory findings consistent with sepsis for which a causative pathogen could not be demonstrated ,20. IntrData regarding the patients’ survival to discharge, any stage of BPD, PDA requiring medical treatment, any stage of ROP, grade 3–4 IVH, and clinical or proven sepsis was recorded from the patients’ records. Follow-up ventilation management and other supportive treatments were provided by the attending neonatologist in accordance with unit protocols. In our unit, the feeding and care of preterm infants and the diagnosis and management of RDS, BPD, patent ductus arteriosus (PDA), and the retinopathy of prematurity (ROP) were carried out in accordance with Turkish Neonatology Society guidelines ,17,19,22clinicaltrials.gov (accessed on 12 May 2019) (NCT04191239).Written informed consent was obtained from the patients’ families. The study was approved by the Ankara City Hospital Ethics Committee (E1-19-198) in accordance with the Helsinki Declaration and prospectively registered at t-test was used for comparisons of repeated measures within subjects and the Mann–Whitney U test was used for comparisons between the two different groups. Statistical significance was accepted at p < 0.05. The data were analyzed using SPSS for Windows. Descriptive statistics are shown as frequency and percentage, mean and standard deviation, or median and range. A paired samples The study included a total of 28 patients, 14 in the PRVC group and 14 in the bilevel VG group. The mean birth weight was 876 g (range: 530–1170) and the mean gestational age was 26.4 weeks (range: 24–29). The characteristics of the patients are shown in 2 and PIP3) was lower after ventilation in bilevel VG mode than in PRVC mode . After 2 h of bilevel VG ventilation, the mean heart rate decreased from 149/min to 140/min (p = 0.001) and the oxygen saturation increased from 91% to 94% (p = 0.01). There were no significant differences in mean airway pressure, respiratory rate, or blood gas values. The patients’ peak inspiratory pressure (PIPAs shown in 2 retention. CO2 excretion is determined by VT and the respiratory rate. Volume-targeted ventilation (VTV) strategies aim to provide a consistent VT. VTV has been used for many years in pediatric and adult patients, and tidal volume-targeted synchronized ventilation modes are currently the most recommended strategy for ventilating preterm infants.Mechanical ventilation is used when preterm infants have insufficient respiratory effort or in the presence of apnea or CO® Carescape R860 model ventilator are two examples of adaptive target schemes for achieving target VT. This study aimed to compare and evaluate the safety and feasibility of these two modes for use in NICUs equipped with this ventilator model.The bilevel VG mode and PRVC mode of the GEThe literature includes very few studies of these modes and much less information about their use in neonates. 2/FiO2 and PaO2) were significantly better in the PRVC group (p = 0.004). The dead space volume/tidal volume (VD/VT) and inspiratory airway pressures were significantly lower in the PRVC group. In addition, all inflammatory parameters  were significantly lower in the PRVC group. Therefore, it was concluded that the PRVC mode had positive effects during OLV in thoracic surgery [In a study investigating the effects of PRVC and VG ventilation modes on oxygenation parameters, airway pressures, and immunomodulation during one-lung ventilation (OLV) in 70 adult patients undergoing thoracic surgery, oxygenation parameters  more than VCV. A target Vtilation .A study including 39 older intubated patients with chronic obstructive pulmonary disease compared PRVC and SIMV-VC modes and evaluated the efficacy of PRVC mode and its prevention of pulmonary barotrauma. Assessment of respiratory mechanics, arterial blood gas analysis, and vital signs at 2–4 h and at 48 h showed that PRVC resulted in rapid improvement in arterial blood gas parameters while maintaining low peak inspiratory pressure .Kıhtır et al. evaluated 61 children (median age 12) with acute respiratory failure ventilated with PRVC or pressure-control (PC) modes. PC ventilation mode was used on 40 (65.6%) patients and PRVC mode was used on 21 (34.4%) patients. Forty-four patients (72.1%) had hypercapnic respiratory failure and twenty-eight patients (45.9%) had hypoxemic respiratory failure. Although the PC ventilation mode was preferred more frequently in hypoxemic respiratory failure, no difference was found in terms of MV duration, length of stay in the pediatric intensive care unit, and mortality between the two respiratory modes. It was stated that PRVC mode can be used as a safe option for units that do not have sufficient experience in using PC ventilation mode .Another study compared PRVC and SIMV modes in 212 preterm infants under 1250 g who received mechanical ventilation in the first 6 h of life. There was no significant difference between the SIMV and PRVC groups in terms of infants alive and extubated on day 14 (41% vs. 37%), the duration of mechanical ventilation in survivors (median 24 vs. 33 days), or the proportion of infants not needing supplemental oxygen at postmenstrual 36 weeks (57% vs. 63%). Mode change due to unsuccessful ventilation was more frequent in the SIMV group (33%) than in the PRVC group (20%), but the inclusion of this unfavorable outcome did not change the overall result. The authors concluded that PRVC ventilation had no effect on the extubation time compared to SIMV .p < 0.005). In the subgroup analysis of infants under 1000 g, the PRVC group had shorter ventilation duration and a lower incidence of hypotension (p < 0.005). It was reported that PRVC ventilation can be used safely in newborns and may contribute to a lower complication rate [In a study comparing PRVC and IMV modes in 60 neonates under 2500 g who required mechanical ventilation, the duration of ventilation and the incidence of BPD were found to be similar. The incidence of IVH grade 3 or higher was lower in the PRVC group (ion rate .2 values, and air leaks. In our practice, we prefer VG and volume-targeted modes. We planned this study both because GE-brand ventilators have not been evaluated in neonatal and preterm infants in the medical literature and because these devices are available and being used in some hospitals.Volume-targeted, volume-guaranteed ventilation is currently the most valid ventilation mode for preterm infants . Some deIn recent trials, valuable information regarding HFO ventilation in preterm infants has been provided. Although there is information that HFO can reduce BPD when used as the first mode in premature babies, more studies need to be designed on this subject ,30.® Carescape R860 model ventilator in very preterm infants. Moreover, the infants were diagnosed and treated by experienced staff with strictly adapted guidelines. To our knowledge, this is the first study comparing these two modes driven by the GEThe small number of patients is the main limitation of this study. Our results do not indicate that one of these modes is superior or more useful than other modes. However, devices and modes not previously used in neonatal studies were used as treatment options in very small preterm infants and were shown to be safe and applicable in this group. Another limitation may be our selection criteria because the infants included in the study are preterm infants with surfactant-treated RDS. The limited gestational age and the underlying cause may have altered the results. Larger studies including infants with different gestational ages and conditions that lead to intubation and invasive mechanical ventilation are required. In conclusion, both the PRVC and bilevel VG modes of GE ventilators can be used safely in preterm infants, and although the difference may not be very pronounced, bilevel VG mode was associated with more favorable early clinical findings. Studies including more patients and comparing them with other modes will clarify and provide further evidence on this subject.


Six studies with a total of 166 participants were considered after the full texts of 61 potential reports were reviewed. This research included in the review covered the period from 1998 to 2021 in retrospect. According to the current systematic review and meta-analysis, transparent aligners had a successful outcome. In mild to moderate cases, aligner treatment appears to have a significant advantage in terms of efficiency (treatment time); nonetheless, insufficient evidence of efficacy was observed based on multiple cross-sectional investigations. When compared to traditional brackets, clear aligners provided a more stable course of treatment.The aim of this study was to evaluate the efficacy and efficiency of orthodontic treatment using clear aligner therapy (CAT). This efficiency was measured using the Peer Assessment Rating (PAR) index, the American Board of Orthodontics (ABO) index, or the similarity between the final ClinCheck and the final scanned models. A search was done electronically between 1998 and 2021 using the Cochrane Library, PubMed, and Google Scholar databases. Three reviewers individually rated the articles. The ROBINS tool and the Cochrane risk of bias tool were used to evaluate the quality of observational research and randomized controlled trials, respectively. The degree of certainty for each selected outcome was evaluated using the grading of recommendations assessment, development, and evaluation (GRADE) approach. Although their underlying concept dates back to the early 20th century, transparent aligners are not a particularly novel orthodontic treatment option. Starting with Remensnyder's  "Flex-O-Material and methodologyIn compliance with PRISMA Guidelines 2020, the study was carried out using the checklist below.Eligibility CriteriaThe study's inclusion criteria called for:• Systemically and mentally healthy patients with permanent dentition (minimum age of 15 years), who had received clear aligner orthodontic treatment.· Clear aligners were used to treat the patient.Exclusion criteria contain studies including:• Patients with mixed or deciduous teeth.• Those who have not received clear aligner orthodontic therapy.• Those with systemic illnesses that raise their risk of infection and affect their findings.Participants/PopulationParticipants had to meet the minimum chronological age requirement of 15 years and be in overall and mental good health. They are also required to have received clear aligner orthodontic treatment.Exclusion criteria for research included:• Patients with mixed or deciduous teeth.• People who had not received clear aligner orthodontic treatment. • Patients with systemic disorders, which increase the risk of infections and have negative effects on outcomes.• Patients receiving clear aligners treatment.Comparator(s)/ControlSelf-evaluation was conducted both before and after clear aligner therapy (CAT), which serves as the baseline.Types of Study IncludedIncluded papers: Records of orthodontic treatment with clear aligners for dental malocclusion published in the English language, prospective cohort studies, retrospective studies, and randomized and non-randomized clinical trial studies.Omitted studies: Reviews, case series studies, reviews, case reports (in-vitro), , and others were not included.OutcomeThe effectiveness and efficacy of orthodontic treatment carried out using CAT were the main topics of this systematic study. This efficiency was assessed using the Peer Assessment Rating (PAR) index, the American Board of Orthodontics (ABO) index, or the equivalence between the Final ClinCheck and the final scanned models.www.crd.york.ac.uk/Prospero, logs: CRD42023378828).Priority Reporting Items of the Extended Meta-Analysis for Systematic Reviews and Diagnostic Test Accuracy (PRISMA-DTA) guidelines were performed as per the protocol for any systematic review and are registered in the National Institutes of Health database . Two studies were included, which were homogenous and were not significant. Meta-analysis was used on time point, which was heterogeneous.DiscussionIn previous studies, 26 limited the indications for treatment with clear aligners to cases of simple, mild malocclusion, but advances in factors critical to the quality and function of many aligners have led to the possibility of using aids such as divots and other means of movement, their different properties, and the possibilities of different types of tooth movements -13.The availability of 3D scanners, 3D printers, and a variety of validated 3D printing materials in dental offices and with orthodontic treatment planning software has enabled clinicians to fabricate their patients' aligners directly, or in their clinics, without having to collaborate with CA providers -20. In aJoe et al. reported that 44 patients (mean age: 26.4 ± 7.7 years) were randomly assigned to either the fixed labial appliance or the clear aligner group in a 1:1 ratio. Both groups have similar baseline characteristics: Fixed appliance mean crowding was 2.1 ± 1.3 mm versus clear aligner mean crowding of 2.5 ± 1.3 mm; fixed appliance mean mandibular incisor inclination was 90.8 ± 5.4 u vs 91.6 ± 6.4u for the clear aligner group. Mandibular incisor proclination was 5.3 ± 4.3u with fixed appliances. The mandibular incisors were proclined by 3.4 ± 3.2u using clear aligners. There was no statistically significant difference between the two groups (p>0.05). The study concluded that there was no difference in the amount of mandibular incisor proclination induced by transparent aligners versus fixed labial appliances in mild cases .The study conducted by Orfeas et al. evaluated the accuracy of various tooth movements during orthodontic treatment. They observed that the horizontal shifts of all incisors were precise, showing minimal differences (ranging from 0.20 mm to 0.25 mm) between the anticipated and actual movements. However, vertical adjustments, especially the downward repositioning (intrusion) of upper central incisors, exhibited lower accuracy. The median variance between predicted and achieved intrusion was 1.5 mm, indicating inconsistencies between the two. Additionally, the study noted that accomplished tooth rotations were notably smaller than predicted rotations. Notably, the maxillary canines displayed the most significant difference, with a 3.05-degree gap between anticipated and achieved rotation .LimitationsSince there are so few RCTs and a large research gap between the studies, more research could be further conducted.It is evident that the field of orthodontics is also developing with technological innovation, with methods such as 3D printing, teleorthodontics, and biopolymers, leading to the changes made to the orthodontic landscape. However, it is impossible to adopt all the changes that are occurring at once; caution and restraint are the most crucial guidelines that must be followed. On the basis of multiple cross-sectional studies, the results of the systematic review demonstrated that CAT was a more successful way of treatment for mild to moderate instances. The aforementioned conclusion will need to be supplemented by additional studies due to the constantly evolving methodologies used in CAT.


KRAS gene mutation and relatively indolent biological behaviour. As newly diagnosed cases, rigorous and regular follow-up is necessary. In addition, a literature review was performed from 1978 to 2022, and 97 cases of papillary renal neoplasms with reverse polarity were identified and analysed.Papillary renal neoplasm with reverse polarity (PRNRP) is a rare renal tumour and was newly named in 2019. This study reported a case of a 30-year-old female patient with a left renal tumour without any clinical symptoms and whose CT scan of her left kidney showed a mass of 2.6 cm×2.3 cm, which was considered to be renal clear cell carcinoma. Laparoscopic partial nephrectomy was performed, and histopathology and immunohistochemistry confirmed papillary renal neoplasm with reverse polarity, which had unique clinicopathological features, immunophenotype,  Papillary renal neoplasm with reverse polarity is a newly reported papillary renal tumour that accounts for approximately 4% of all previously diagnosed papillary renal cell carcinomas (PRCC) . This tuA 30-year-old female patient was admitted to the hospital with a left renal mass found on physical examination. During the course of the disease, there was no low back pain, haematuria, frequent urination and pain, dizziness, palpitations, fever or chills. The patient had not received any specific treatment previously and followed a healthy diet and lifestyle and had no family history of the disease or similar diseases. The patient’s vital signs were normal. There was no swelling, tenderness or pain induced by tapping over either kidney area. Urological ultrasound showed a moderate echogenic mass of approximately 2.6 cm×2.3 cm in the middle and upper parts of the left kidney, with a clear boundary and regular shape and no blood flow signal Figure 1The PubMed database was searched for case reports and case series of papillary renal cell carcinoma and papillary renal neoplasm with reverse polarity published between 1978 and 2022. Using the following keywords:  or (oncocytic PRCC) or  or (PRNRP), 403 results were retrieved. After removing unrelated studies, 11 publications describing 97 cases were finally identified Table 1.Papillary renal neoplasm with reverse polarity is a rare type of renal neoplasm reported recently. In 2003, Allory et al. found that some papillary renal cell carcinomas had a good prognosis and called it “oncocytoid-type papillary renal cell carcinoma” . LefevreAccording to the study reported by AI-Obaidy et al., the incidence of PRNRP was similar in males and females, and the age ranged from 46 to 80 years, with an average age of 64 years . HoweverPRNRP usually has no specific clinical symptoms, thus posing significant preoperative diagnostic challenges. Imaging examinations do not provide much diagnostic information because of their rarity. At present, there is a lack of literature reports on the imaging features of PRNRP, and more data need to be collected and further explored. Histopathology and immunohistochemistry are the gold standard for the diagnosis of PRNRP. Chang et al. proposed the following four diagnostic criteria: (I) Mainly protruding thin papillary or tubular papillary growth; (II) Focal or diffuse interstitial vitrification; (III) Eosinophilic fine granular cytoplasm; (IV) The tumour nuclei were neatly arranged on the top of the cytoplasm far away from the basement membrane, showing the characteristics of “reverse polarity”, with the same size and low nuclear grade . This paImmunophenotypically, PRCC strongly expressed vimentin and p504s, but did not express GATA3 and 34βE12. PRNRP strongly expressed GATA3 and KRT7, and expressed p504s to varying degrees, and could express 34βE12, but could not express vimentin. This tumor strongly expressed KRT7 and partially expressed p504s, but did not express CD10, which was consistent with the PRCC phenotype. However, unlike other PRCC subtypes, PRNRP typically expresses GATA3. PRNRP does not express vimentin, CD10, CAIX, CD117, TFE-3, ALK, etc, which is helpful for differential diagnosis from other rare types of renal cell carcinoma. The low proliferation index of Ki-67 suggests that it has a good prognosis. The above immunophenotypes were consistent with those reported in the literature  analysis showed that 32% (14/44) of papillary renal tumours with reverse polarity had abnormalities in chromosomes 7 and 17, and only 2 cases (2/44) had chromosome Y deletion  classification of renal tumours . HoweverThe original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.The studies involving human participants were reviewed and approved by the Ethics Committee of Chengdu Second People’s Hospital. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article. Written informed consent was obtained from the participant/patient(s) for the publication of this case report.XT was the patient’s urologists, reviewed the literature and contributed to manuscript drafting. XZ reviewed the literature and prepared figures. WW, QC and CH were responsible for the revision of the manuscript for important intellectual content. All authors issued final approval for the version to be submitted. All authors contributed to the article and approved the submitted version.


Indoor air pollution has been reported to have adverse effects on the eye; however, the health effects of exposure to cooking with solid fuels on visual impairment remain unclear in China.We aimed to examine the association between cooking with solid fuels and visual impairment, including distance visual impairment (DVI) and near visual impairment (NVI).Data were obtained from the China Health and Retirement Longitudinal Study, a nationwide survey of adults aged over 45 years who were enrolled in 2011 (Wave 1) and followed up in Wave 2 (2013), Wave 3 (2015), and Wave 4 (2018). We used Cox proportional hazards models to determine the association between solid fuels use and visual impairment. Additionally, the impact of switching cooking fuel types on vision function were examined through wave-specific data analysis (Wave 1 and Wave 4). Interaction and subgroup analyses were performed to explore the potential effect modifiers. Data were collected using the stratified multistage random sampling method and further analyzed using SPSS 27.0 and R 4.2.1 statistical software packages.P=.52). In subgroup analysis, we found that cooking with solid fuels increased the risk of DVI in participants younger than 65 years , men , urban residents , and smokers . By contrast, negative effects of cooking with solid fuels on NVI were found in nonsmokers  and urban residents .A total of 9559 middle-aged and older Chinese adults without visual impairment at baseline were included in the study, with 51.2% (n=4914) of the participants reporting that they cooked with solid fuels. During the follow-up period, 2644 (27.5%) and 3130 (32.6%) participants developed DVI and NVI, respectively. Compared with the clean fuel users, participants who cooked with solid fuels had a higher risk of DVI  and NVI . In addition, switching the cooking fuel type from clean to solid fuels was associated with an elevated risk of DVI  and NVI  compared to persistently using clean fuels during the follow-up period, although no protective effect of switching from solid to clean fuels on NVI was found (Cooking with solid fuels was associated with an increased risk of visual impairment among middle-aged and older Chinese adults. These findings indicate that promoting the utilization of clean fuels is conducive to reducing the burden of visual impairment for the public. These emissions would stimulate the production of reactive oxygen species, which can seriously impair the viability of eye cells and accelerate oxidation of the lens [Incomplete and inefficient combustion of solid fuels  is the primary cause of indoor air pollution, affecting approximately half the global population . Prolongthe lens . MoreoveEye problems such as tearing, redness, itching, and stinging are widely reported to be linked to indoor air pollution ,4. A recAn estimated 2.2 billion people globally have visual impairments, with nearly half of these cases being preventable or untreated . UntreatGiven the widespread use of solid fuels in China , evidencTo fill the above knowledge gap on the link between solid fuel use and visual impairment among Chinese adults, we performed this study to assess the longitudinal association between self-reported cooking with solid fuels and visual impairment in a nationally representative sample obtained from the China Health and Retirement Longitudinal Study (CHARLS). This prospective cohort study assessed the impact of indoor air pollution on visual impairment among middle-aged and older Chinese adults from 2011 to 2018 for the first time and also examined the effects of switching cooking fuel types on vision function over time.This nationwide population-based cohort study utilized data from the CHARLS, which was implemented by the National School of Development of Peking University. An unbiased and representative sample was obtained by proportional and multistage stratified sampling . In the We used the data from all four waves to examine the relationship between solid fuel use and visual impairment; a total of 9559 individuals were selected based on the following exclusion criteria: (1) 650 lost to follow-up in Wave 2, Wave 3, and Wave 4; (2) 171 had missing data on cooking fuels in Wave 1; (3) 126 self-reported other cooking fuels in Wave 1; (4) 1376 had missing data on visual function in Wave 1; (5) 5343 had visual impairment in Wave 1; and (6) 443 had missing data on visual function during the follow-up period (Wave 2/Wave 3/Wave 4) .In addition, we used the wave-specific data of Wave 1 and Wave 4 to examine the association between switching the fuel type and visual impairment; 7998 individuals were selected based on the following exclusion criteria: (1) 3310 lost to follow-up in Wave 4; (2) 116 had missing data on cooking fuels in Wave 1; (3) 103 self-reported other cooking fuels in Wave 1; (4) 1016 had missing data on visual function in Wave 1; (5) 4579 had visual impairment in Wave 1; (6) 452 had missing data on visual function in Wave 4; (7) 19 had missing data on cooking fuels in Wave 4; and (8) 115 self-reported other cooking fuels in Wave 4.Individuals’ distance vision was assessed by self-reported visual status when recognizing friends across the street  and personal near vision was assessed by self-reported visual status when reading regular newspapers . Possible responses to these questions were “poor,” “fair,” “good,” “very good,”, and “excellent.” Those reporting “poor” for near and distance vision were defined as having near visual impairment (NVI) and distance visual impairment (DVI), respectively. Those reporting “excellent,” “very good,” “good,” or “fair” were defined as having no visual impairment (reference group). Visual impairment assessment and categorization were performed in accordance with previous studies -17.The question “What are your main sources of cooking fuels?” was used to assess indoor cooking fuel types. At baseline, reporting “coal,” “crop residue,” and “wood” was defined as cooking with solid fuels. The main types of solid fuels were classified into coal and biomass (“crop residue” and “wood”). Reporting “liquefied petroleum,” “natural gas,” “electricity,” and “marsh gas” was defined as cooking with clean fuels. We compared data from respondents who reported cooking with clean fuels to those of the solid fuel users. In addition, we collected information on self-reported cooking fuel types in Wave 4, which had an additional choice of “do not cook” compared to the answers regarding the baseline question. We categorized “do not cook” as clean fuel, and assessed the association of switching cooking fuel types with visual impairment. Therefore, participants could be classified as switching from solid fuels to clean fuels or from clean fuels to solid fuels.2) [Baseline demographics  and health-related status  were included as covariates in our analyses. We classified cohabitation and marriage as married. Education level was divided into illiteracy (0 years) and others (≥1 year). Residence was divided into rural and urban areas . BMI was2) . Alcoholt tests. Categorical variables were summarized as frequencies (percentages) and were compared with the χ2 test. A Cox proportional hazard model was performed to assess the effects of solid fuel use on visual impairment. We also compared data of participants who switched from clean fuels to solid fuels or from solid fuels to clean fuels with those who persistently used clean or solid fuels through wave-specific analysis. The proportional hazard assumption was examined using the Schoenfeld residual test. Model 1 was an unadjusted model. Model 2 was adjusted for age, gender, BMI, marital status, education level, residence, alcohol drinking, smoking status, and sleep duration. Model 3 was further adjusted for hypertension, dyslipidemia, diabetes, cancer, chronic lung disease, and heart disease based on Model 2. The percentage of missing covariates was less than 5% for all covariates, which conformed to an arbitrary missingness pattern. We used multiple imputation to account for these missing values. The Markov chain Monte Carlo method was used to analyze the complete data set and interpolate each missing value five times to obtain five complete data sets. Statistical analysis was then performed on each filled data set separately and the combined results of the five analyses were used to select the data set with the largest relative efficiency value. Additionally, we performed subgroup analyses and interactions analysis stratified by age, sex, residence area, and smoking status to assess potential effect modifications. The sensitivity analysis was conducted by excluding participants who reported not cooking in Wave 4 to ensure that our findings were robust. Cox proportional hazards model results are presented as hazard ratios with 95% CIs. Statistical analyses were performed using SPSS 27.0 and R 4.2.1 software. Two-tailed P values less than .05 were considered statistically significant.The baseline characteristics are described according the type of cooking fuels. Continuous variables were summarized as mean (SD) and were compared with independent The CHARLS was approved by the Research Ethics Committee of Peking University (IRB00001052-11015). This survey was anonymous and the answers are protected by privacy law. Written informed consent clarifying the study purposes was obtained from each participant before completing the interview.P<.001). Additionally, significantly more individuals with hypertension, diabetes, and dyslipidemia used clean fuels for cooking rather than solid fuels .A total of 9559 participants without visual impairment at baseline were included. The average age of included participants was 57.7 (SD 9.5) years and 50.3% of them were women. Overall, 51.2% (n=4914) of the participants primarily cooked with solid fuels , and 15.During the follow-up period, 2644 (27.5%) and 3130 (32.6%) of the 9599 total participants reported DVI and NVI, respectively . The effP=.52). After excluding participants who reported not cooking in Wave 4, our findings remained robust (see Through the wave-specific data, we found that participants who switched their cooking type from clean to solid fuels had a 51% elevated risk of DVI and a 39% elevated risk of NVI compared with the persistent clean fuel users. However, there was no evidence of an impact of switching from solid to clean fuels on NVI (bust see .We performed analyses of interactions and subgroups on the relationship between using solid fuels for cooking and visual impairment in Model 3 . We founThis study demonstrated that cooking with solid fuels increased the risks of visual impairment, with an adverse effect of solid fuel use found for both DVI and NVI, especially for participants living in urban areas. Moreover, switching from clean to solid fuels was demonstrated to increase the risk of DVI and NVI compared to the persistent use of clean fuel. These main findings are consistent with evidence from previous studies conducted in countries neighboring China. In India, the older population, who are highly reliant on using unclean cooking fuel, had a higher prevalence of visual impairment . In Nepa2.5 is the primary pollutant in solid fuel smog, which represents a mixture of thousands of harmful chemicals such as heavy metals and polycyclic aromatic hydrocarbons [3 rise in ambient PM2.5 exposure, the risk of glaucoma increased by 6% [The essential mechanisms of the impacts of solid fuel utilization on visual impairment are undefined . One posocarbons . A previed by 6% . Free raed by 6%  as the led by 6% ,28. On ted by 6% . Anothered by 6% ,31. Heated by 6% ,33, whiced by 6% , depressed by 6% , and coged by 6% , which wPrevious studies observed that women were more likely to develop eye diseases linked to solid fuel use -39, suggMore harmful impacts of cooking with solid fuels on NVI were noted among urban residents. Rural areas are usually less economically developed and have a lower population density than urban areas. Higher industrialization in urban areas may increase the risk of visual impairment since rapid industrialization would result in worse indoor air pollution and associated health outcomes . AdditioSimultaneously, an interesting result emerging from our study was that switching from clean fuels to solid fuels could increase the risk of visual impairment compared with the continued use of clean fuels. The switch of cooking fuels from clean fuels to biomass fuels might be related to the migration from urban to rural areas among older people in China, which has been a prevalent trend in recent years ,44. OldeThis study has several limitations. First, with the rapid development of modernization, urbanization, and industrialization in China over the past three decades, more and more rural residents have gradually begun to use clean energy. Some of the participants in this study may have switched from solid to clean fuels prior to the baseline assessment, which would lead to an underestimate of the impact of solid fuels on visual function. Second, individual visual acuity and the exposure level to household pollutants cannot be accurately estimated due to data unavailability; thus, further research should use an objective assessment to verify the data and adjust for lead-time bias . Third, Overall, our study demonstrated that using solid fuels for cooking was significantly associated with elevated risks of visual impairment among Chinese adults aged over 45 years, especially among participants living in urban areas. Furthermore, switching the cooking fuel type from clean to solid fuels may also significantly increase the risk of visual impairment. Therefore, this study highlights the value of promoting the availability of household clean fuels and encouraging the consistent use of clean fuels to decrease the burden of visual impairment.