In Situ Formation ZnIn2 S4 /Mo2 TiC2 Schottky Junction for Accelerating Photocatalytic Hydrogen Evolution Kinetics: Manipulation of Local Coordination and Electronic Structure.

Regulating electronic structures of the active site by manipulating the local coordination is one of the advantageous means to improve photocatalytic hydrogen evolution (PHE) kinetics. Herein, the ZnIn2 S4 /Mo2 TiC2 Schottky junctions are designed to be constructed through the interfacial local coordination of In3+ with the electronegative O terminal group on Mo2 TiC2 based on the different work functions. Kelvin probe force microscopy and charge density difference reveal that an electronic unidirectional transport channel across the Schottky interface from ZnIn2 S4 to Mo2 TiC2 is established by the formed local nucleophilic/electrophilic region. The increased local electron density of Mo2 TiC2 inhibits the backflow of electrons, boosts the charge transfer and separation, and optimizes the hydrogen adsorption energy. Therefore, the ZnIn2 S4 /Mo2 TiC2 photocatalyst exhibits a superior PHE rate of 3.12 mmol g-1 h-1 under visible light, reaching 3.03 times that of the pristine ZnIn2 S4 . This work provides some insights and inspiration for preparing MXene-based Schottky catalysts to accelerate PHE kinetics.

Real world outcomes of lenalidomide or bortezomib maintenance in patients with multiple myeloma not undergoing stem cell transplantation.

Maintenance is one form of long-term therapies in multiple myeloma (MM). Lenalidomide and bortezomib are two commonly used options. The role of maintenance in patients not undergoing transplant remains unclear. A total of 248 newly diagnosed MM patients who received over 180 days of any standard-of-care induction therapy and did not receive autologous stem cell transplantation were included. Patients either receive lenalidomide, bortezomib or no maintenance. Patterns of usage, survival benefit, discontinuation status were analyzed. 93, 99 and 56 patients received no, lenalidomide (Len) and bortezomib (Bor) maintenance respectively. Patients receiving Bor had a higher incidence of traditional high-risk cytogenetics (14.0% (No) vs 14.1% (Len) vs 41.1% (Bor), P < 0.001). Len maintenance conferred a superior progression-free survival (PFS) and overall survival (OS) compared to no maintenance (median PFS, 60.1 vs 26.9 months, P = 0.003; median OS, NR vs 56.7 months, P = 0.046), with a near independent impact on PFS (adjusted HR 0.580, P = 0.058). The PFS and OS benefit of Len maintenance was seen in subgroups of ISS stage I/II, traditional standard-risk cytogenetics, and pre-maintenance < CR. Bor maintenance did not confer PFS or OS benefit for the entire cohort, but improved OS in patients with pre-maintenance < CR. Discontinuation due to toxicity was recorded in 11.1% and 8.9% of patients receiving Len or Bor maintenance respectively. Our study supports lenalidomide maintenance as the standard-of-care in MM patients not undergoing transplant. Further studies are warranted for bortezomib maintenance in the non-transplant setting, and better maintenance strategy is needed for patients with adverse prognostic factors.

A ratiometric fluorescent probe for fast detection and bioimaging of formaldehyde.

A novel ratiometric probe (SWJT-10) based on isophorone derivatives has been designed and synthesized for the detection of formaldehyde (FA). This probe displayed an obvious ratiometric fluorescence response to FA with a blue shift from the NIR (680 nm) to the yellow light region (600 nm) in aqueous solution. And it showed good selectivity, high sensitivity and a fast response to FA (less than 5 s) due to a new recognition mechanism. Moreover, SWJT-10 has been applied to monitor FA in living cells and zebrafish.

Identification of bibenzyls and evaluation of imitative wild planting techniques in Dendrobium officinale by HPLC-ESI-MSn.

Dendrobium officinale is a traditional Chinese herb with beneficial properties. Modern pharmacological studies show that bibenzyl is one of the antitumor active ingredients, but there is no effective quality control method for identifying ingredients. In this study, the composition of bibenzyls in Dendrobium officinale was studied by high-performance liquid chromatography coupled with electrospray ionization multistage mass spectrometry (HPLC-ESI-MSn ). A total of nine isolated bibenzyls and their glycosides, 22 bis (bibenzyls), and two phenylpropanol bibenzyl derivatives were identified. The results of HPLC characteristic chromatogram analysis and statistical analysis showed that the relative content of bibenzyls in wild imitation cultivation of samples had been significantly higher than that in greenhouse cultivation. In addition, the relative content of bibenzyls increased with the growth of the original plant. This study provided a scientific reference for controlling the quality of bibenzyls in Dendrobium officinale, developing the cultivation technology and improving the quality of Dendrobium officinale. HIGHLIGHTS: HPLC-ESI-MS/MS method for the analysis of bibenzyls and bis (bibenzyls) in Dendrobium officinale. Easy-to-use method facilitating rapid measurement of large sample quantities. The method requires only small volumes of samples for the analysis. Applicable for the establishment of Chinese medicine studies and the quality control standard of Chinese herbs.

Diagnosis and Management of Idiopathic Hypothalamic Dysfunction: A Case Series and Systematic Review.

Introduction Idiopathic hypothalamic dysfunction (IHD) is a rare syndrome with heterogeneous clinical symptoms. This study aimed to systematically review the clinical features and potential treatment of IHD based on our case series and literature. Methods We analysed six recently diagnosed cases of IHD in Peking Union Medical College Hospital and conducted a systematic review of IHD case studies published before 25 August 2021, using the PubMed/Medline database. All 12 articles that met the definition of IHD and provided individual clinical data were reviewed. Results Of the 19 cases reviewed (13 from the literature and 6 from our centre), the median age at onset was 6 years. Obesity/weight gain (n = 14, 73.7%) and electrolyte abnormalities (n= 14, 73.7%) were the most common hypothalamic physiological dysfunction, followed by autonomic dysregulation (n = 13, 68.4%) and adipsia (n = 13, 68.4%). The most common initial symptom of young patients was obesity/weight gain, whereas the initial symptoms of the three adult patients were hypothalamic amenorrhoea, delayed sexual development and polydipsia. 11 (57.9%) patients had obesity, and three of our patients were diagnosed with metabolic syndrome in late adolescence or early adulthood. Three of our cases diagnosed with growth hormone deficiency received growth hormone therapy, which exerted positive effects on growth promotion and weight stabilisation. Conclusion Although obesity/weight gain was the most common symptom of IHD, uncommon initial symptoms such as electrolyte abnormalities and sexual disorders also require attention, especially in patients with late childhood- or adult-onset IHD. Consistent monitoring of metabolic profiles is recommended. Positive effects of growth hormone replacement therapy on growth and weight were observed, but more extensive cohort studies are required to confirm its efficacy and safety.

Recent progress on the synthesis of metal alloy nanowires as electrocatalysts.

Benefiting from both one-dimensional (1D) morphology and alloy composition, metal alloy nanowires have been exploited as advanced electrocatalysts in various electrochemical processes. In this review, the synthesis approaches for metal alloy nanowires are classified into two categories: direct syntheses and syntheses based on preformed 1D nanostructures. Ligand systems that are of critical importance to the formation of alloy nanowires are summarized and reviewed, together with the strategies imposed to achieve the co-reduction of different metals. Meanwhile, different scenarios that form alloy nanowires from pre-synthesized 1D nanostructures are compared and contrasted. In addition, the characterization and electrocatalytic applications of metal alloy nanowires are briefly discussed.

Assessing the association between smoking and hypertension: Smoking status, type of tobacco products, and interaction with alcohol consumption.

Background: The association between tobacco use and hypertension risk has been extensively researched but remains controversial, and few existing studies have considered the role of tobacco type and dosage response in this association. In this context, this study aims to provide epidemiological evidence for the possible relationship between tobacco smoking and future hypertension risk, with the tobacco type and consumption dose into consideration. Methods: This study was based on 10-year follow-up data from the Guizhou Population Health Cohort conducted in southwest China. Multivariate Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals [95% confidence intervals (CIs)], and restricted cubic spline analyses were performed to visualize the dose-response association. Results: A total of 5,625 participants (2,563 males and 3,062 females) were included in the final analysis. Heavy smokers of machine-rolled cigarettes had an elevated hypertension risk compared with non-smokers (HR: 1.50, 95% CI: 1.05-2.16). The interaction effects of heavy smoking-heavy drinking patterns increased the future hypertension risk, with an adjusted HR of 2.58 (95% CI: 1.06-6.33). Conclusion: This study did not find a significant association between overall tobacco use status and the risk of hypertension. However, heavy machine-rolled cigarette smokers had a statistically significant increased risk of hypertension compared with non-smokers, and a J-shape association has been found between the average daily consumption of machine-rolled cigarettes and the risk of hypertension. Besides, tobacco and alcohol consumption jointly increased the long-term hypertension risk.

Hyperprolactinaemia is common in Chinese premenopausal women with breast diseases.

Purpose: Hyperprolactinaemia has been proposed to play a role in breast lesions pathophysiology. Thus far, controversial results have been reported for the relationship between hyperprolactinaemia and breast lesions. Moreover, the prevalence of hyperprolactinaemia in a population with breast lesions is scarcely reported. We aimed to investigate the prevalence of hyperprolactinaemia in Chinese premenopausal women with breast diseases, and explore the associations between hyperprolactinaemia with different clinical characteristics. Methods: This was a retrospective cross-sectional study performed in the department of breast surgery of Qilu hospital of Shandong University. Overall, 1,461 female patients who underwent the serum prolactin (PRL) level assay before breast surgery from January 2019 to December 2020 were included. Patients were divided into two groups: before and after menopause. Data were analyzed using SPSS 18.0 software. Results: The results showed an elevated PRL level in 376 of the 1,461 female patients with breast lesions (25.74%). Furthermore, the proportion of hyperprolactinemia among premenopausal patients with breast disease (35.75%, 340/951) was significantly higher than among postmenopausal patients with breast disease (7.06%, 36/510). In premenopausal patients, the proportion of patients with hyperprolactinaemia and the mean serum PRL level were significantly higher in those diagnosed with fibroepithelial tumours (FETs) and in younger patients (aged < 35 years) than in those with non-neoplastic lesions and in those aged ≥ 35 years (both p < 0.05). Especially, the prolactin level exhibited steady ascending tendency for positive correlation with FET. Conclusion: Hyperprolactinaemia is prevalent in Chinese premenopausal patients with breast diseases, especially in those with FETs, which implies a potential association, to some extent, between the PRL levels in various breast diseases.

Untargeted metabolomic analysis of metabolites related to body dysmorphic disorder (BDD).

Body dysmorphic disorder (BDD) is a disorder associated with depression and eating disorders. It often arises from minor defects in appearance or an individual imagining that he or she is defective. However, the mechanisms causing BDD remain unclear, and its pathogenesis and adjuvant treatment methods still need to be explored. Here, we employed a liquid chromatography-mass spectrometry (LC-MS)-based metabolomics approach to identify key metabolic differences in BDD versus healthy patients. We obtained plasma samples from two independent cohorts (including eight BDD patients and eight healthy control patients). Raw data were analyzed using Compound Discoverer to determine peak alignment, retention time correction, and extraction of peak areas. Metabolite structure identification was also obtained using Compound Discoverer by of accurate mass matching (< 10 ppm) and secondary spectral matching queries of compound databases. Next, multidimensional statistical analyses were performed using the ropls R package. These analyses included: unsupervised principal component analysis, supervised partial Least-Squares Discriminant Analysis, and orthogonal partial Least-Squares Discriminant Analysis. We then identified the most promising metabolic signatures associated with BDD across all metabolomic datasets. Principal component analysis showed changes in small-molecule metabolites in patients, and we also found significant differences in metabolite abundance between the BDD and normal groups. Our findings suggest that the occurrence of BDD may be related to metabolites participating in the following KEGG pathways: ABC transporters, purine metabolism, glycine, serine and threonine metabolism, pyrimidine, pyrimidine metabolism, biosynthesis of 12-, 14-, and 16-membered macrolides, microbial metabolism in diverse environments, biosynthesis of secondary metabolites, and caffeine and insect hormone biosynthesis.

Perturbation of intestinal stem cell homeostasis and radiation enteritis recovery via dietary titanium dioxide nanoparticles.

Small intestinal health and enteritis incidence are tightly coupled to the homeostasis of intestinal stem cells (ISCs), which are sensitive to dietary alterations. However, little is known about the impact of food additives on ISC pool. Here, we demonstrate that chronic exposure to low-dose TiO2 NPs, a commonly used food additive, significantly hampers primary human and mouse ISC-derived organoid formation and growth by specifically attenuating Wnt signal transduction. Mechanistically, TiO2 NPs alter the endocytic trafficking of the Wnt receptor LRP6 and prevent the nuclear entry of ß-catenin. Notably, dietary TiO2 NPs elicit modest chronic stress in healthy intestines and considerably impede the recovery of radiation enteritis by perturbing the homeostasis of ISCs in vivo. Our results identify a health concern of TiO2 NP exposure on ISC homeostasis and radiation enteritis recovery. These findings suggest extra precaution during the treatment of radiation enteritis and provide new insights into food additive-ISC interaction.

Genome-Wide Identification, Evolutionary and Functional Analyses of WRKY Family Members in Ginkgo biloba.

WRKY transcription factors (TFs) are one of the largest families in plants which play essential roles in plant growth and stress response. Ginkgo biloba is a living fossil that has remained essentially unchanged for more than 200 million years, and now has become widespread worldwide due to the medicinal active ingredients in its leaves. Here, 37 WRKY genes were identified, which were distributed randomly in nine chromosomes of G. biloba. Results of the phylogenetic analysis indicated that the GbWRKY could be divided into three groups. Furthermore, the expression patterns of GbWRKY genes were analyzed. Gene expression profiling and qRT-PCR revealed that different members of GbWRKY have different spatiotemporal expression patterns in different abiotic stresses. Most of the GbWRKY genes can respond to UV-B radiation, drought, high temperature and salt treatment. Meanwhile, all GbWRKY members performed phylogenetic tree analyses with the WRKY proteins of other species which were known to be associated with abiotic stress. The result suggested that GbWRKY may play a crucial role in regulating multiple stress tolerances. Additionally, GbWRKY13 and GbWRKY37 were all located in the nucleus, while GbWRKY15 was located in the nucleus and cytomembrane.

The evolving diagnosis and treatment paradigms of multiple myeloma in China: 15 years' experience of 1256 patients in a national medical center.

BACKGROUND: Significant advances in multiple myeloma (MM) over the past 15 years led to exciting changes in the management of MM patients in China, which in turn brought about the early diagnoses, precise risk stratifications, and improved prognoses. METHODS: We summarized the dynamic changes in the management of newly diagnosed (ND) MM in a national medical center, crossing the old and novel drug era. Demographics, clinical characteristics, first-line treatment, response rate, and survival were retrospectively collected among NDMMs diagnosed in Zhongshan Hospital Fudan University from January 2007 to October 2021. RESULTS: Of the 1256 individuals, median age was 64 (range 31-89) with 45.1% patients >65 years. About 63.5% were male, 43.1% were at ISS stage III and 9.9% had light-chain amyloidosis. Patients with abnormal ratio of free light chain (80.4%), extramedullary disease (EMD, 22.0%), and high-risk cytogenetic abnormalities (HRCA, 26.8%) were detected by novel detection techniques. The best confirmed ORR was 86.5%, including 39.4% with CR. Short- and long-term PFS and OS rates persistently increased each year along with increasing novel drug applications. Median PFS and OS were 30.9 and 64.7 months. Advanced ISS stage, HRCA, light-chain amyloidosis and EMD independently predicted an inferior PFS. First-line ASCT indicated a superior PFS. Advanced ISS stage, elevated serum LDH, HRCA, light-chain amyloidosis, and receiving PI/IMiD-based regimen versus PI+IMiD-based regimen independently indicated a poorer OS. CONCLUSIONS: In brief, we illustrated a dynamic landscape of MM patients in a national medical center. Chinese MM patients evidently benefited from newly introduced techniques and drugs in this field.

A Near-Infrared Fluorescent Probe for Recognition of Hypochlorite Anions Based on Dicyanoisophorone Skeleton.

A novel near-infrared (NIR) fluorescent probe (SWJT-9) was designed and synthesized for the detection of hypochlorite anion (ClO-) using a diaminomaleonitrile group as the recognition site. SWJT-9 had large Stokes shift (237 nm) and showed an excellent NIR fluorescence response to ClO- with the color change under the visible light. It showed a low detection limit (24.7 nM), high selectivity, and rapid detection (within 2 min) for ClO-. The new detection mechanism of SWJT-9 on ClO- was confirmed by 1H NMR, MS spectrum, and the density functional theory (DFT) calculations. In addition, the probe was successfully used to detect ClO- in HeLa cells.

[68Ga]Ga-FAPI-04 PET MRI/CT in the evaluation of gastric carcinomas compared with [18F]-FDG PET MRI/CT: a meta-analysis.

OBJECTIVES: To compare the detection rates of [68Ga]Ga-FAPI-04 PET MRI/CT vs. [18F]-FDG PET MRI/CT in gastric cancer. METHODS: An extensive librarian-led literature search of PubMed, Embase, Web of Science, the Cochrane Central Library, and ClinicalTrials.gov was performed. The primary outcomes were sensitivity in patient-based evaluations, detection of lymph node metastases, and peritoneal involvement. RESULTS: Five studies, including 148 participants, were analyzed. [68Ga]Ga-FAPI-04 PET MRI/CT has a comparatively high sensitivity in patient-based evaluations compared with [18F]-FDG PET MRI/CT (risk difference = 0.16, 95% CI 0.09-0.22, P < 0.00001). The [68Ga]Ga-FAPI-04 PET MRI/CT group has a comparatively higher sensitivity in detecting lymph node metastases (RR = 0.15, 95% CI 0.01-0.29, P = 0.04), peritoneal involvement (RR = 0.55, 95% CI 0.38-0.72, P < 0.00001) in gastric cancer than [18F]-FDG PET MRI/CT group. CONCLUSIONS: This systematic review confirmed the advantage of [68Ga]Ga-FAPI-04 PET MRI/CT in gastric cancer. [68Ga]Ga-FAPI-04 PET MRI/CT was superior to [18F]-FDG PET MRI/CT in detecting the primary tumor, lymph node metastases, and peritoneal metastases. More studies are needed for the sensitivity and specificity of [68Ga]Ga-FAPI-04 PET MRI/CT in different pathological types of gastric cancer.

A dual-mode probe based on AIE and TICT effects for the detection of the hypochlorite anion and its bioimaging in living cells.

Based on aggregation-induced emission (AIE) and twisted intramolecular charge transfer (TICT) mechanisms, a fluorescent probe SWJT-12 for the detection of ClO- was designed by using the CN bond as a reactive group. This synthesized probe can react with ClO- in a high aqueous phase, and it shows a large Stokes shift (144 nm) and low biological toxicity. Its limit of detection was calculated to be 0.28 µM. Furthermore, SWJT-12 was successfully used for ratiometric imaging of the exogenous hypochlorite anion in living cells.

The prognostic role of 1q21 gain/amplification in newly diagnosed multiple myeloma: The faster, the worse.

BACKGROUND: The prognostic value of additional copies of chromosome 1q (1q gain/amplification [amp]) in multiple myeloma (MM) remains controversial. In the meantime, the kinetics of the response to MM therapy has long been an area of debate. Few studies have pointed out the relationship of response kinetics with cytogenetic abnormalities (CAs) in MM. METHODS: The authors retrospectively analyzed the data of 1068 real-world newly diagnosed MM patients from a Chinese national medical center. RESULTS: Overall, 405 (51.9%) patients had 1q gain/amp, with aggressive clinical characteristics and significant inferior survival. The variation in copy number (CN) of 1q (CN = 3 or CN >3) had no significant impact on the survival of MM patients with 1q abnormalities. No difference was found in the outcome of 1q gain/amp patients treated with doublet or triplet regimens. Upfront autologous stem cell transplantation could eliminate the adverse prognostic effect of 1q gain but not 1q amp. The duration from diagnosis to the first time achieving very good partial response (VGPR) or better was significantly shorter in patients with 1q gain/amp (77 days vs. 100 days, p = .001). Finally, multifactor regression analysis was performed to construct a new risk stratification model in MM patients with 1q gain/amp, which was validated in the Multiple Myeloma Research Foundation CoMMpass study cohort and worked better than the Revised International Staging System and Second Revision of the International Staging System (Harrell's concordance index: 0.631 vs. 0.598 and 0.537). CONCLUSIONS: In the setting of novel therapy, 1q gain/amp still acts as an independent adverse prognostic factor. Patients with 1q gain/amp achieved VGPR rapidly but had inferior survival.

Downregulated miR-367-3p, miR-548aq-5p, and miR-4710 in Human Whole Blood: Potential Biomarkers for Breast Cancer With Axillary Lymph Node Metastasis.

BACKGROUND: Increasing studies have shown that microRNAs (miRNAs) have great diagnostic value in cancer. Axillary lymph node metastasis (ALNM) is closely related to the prognosis of breast cancer. However, it remains unknown whether miRNAs in whole blood could be promising biomarkers in breast cancer ALNM. METHODS: An miRNA microarray was used to screen potential differentially expressed miRNA candidates in whole blood of three breast cancer patients with ALNM and three without ALNM. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect candidate differentially expressed miRNAs in the whole blood of 109 breast cancer patients. Furthermore, bioinformatics analysis was carried to predict the potential targets and enriched pathway of miRNAs. RESULTS: QRT-PCR validated the fact that miR-367-3p, miR-548aq-5p and miR-4710 are downregulated in breast cancer with ALNM compared to it without ALNM. Receiver operating characteristic (ROC) curve analysis revealed that miR-367-3p, miR-548aq-5p and miR-4710 have good diagnostic values. Notably, the three-miRNA signature showed better predictive value, with an area under ROC curve (AUC) of 0.7414. Bioinformatics analysis revealed that the miRNAs could participate in a complex network and thus be involved in cancer-related pathways. CONCLUSIONS: Our findings support the potential of miR-367-3p, miR-548aq-5p and miR-4710 and the three-miRNA signature as biomarkers for breast cancer with ALNM.

Relationship between meteorological variations, seasonal influenza, and hip fractures in the elderly: A modelling investigation using 22-year data.

With the heavy negative health effect and economic burden of hip fractures in the elderly, the relationship of hip fractures with climate and seasonal influenza has not been quantified explicitly. In this study, we aim to make use of population-based data to evaluate the impact of meteorological factors and influenza activity on the hip fracture admissions for the elderly in Hong Kong from 1998 to 2019. Weekly numbers of admissions for the elderly due to hip fractures were used as the study outcome, and were matched with the meteorological factors included air temperature, relative humidity, solar radiation, and total rainfall. Strain-specific influenza-like illness-positive (ILI+) rates were employed as proxies for seasonal influenza activity. Quasi-Poisson generalized additive model in conjunction with distributed-lag non-linear model was used to elucidate the association of interest. According to the results, a total of 191,680 hip fracture admissions for the elderly aged ≥65 years were recorded over a 22-year span. The cumulative adjusted relative risks of hip fracture were 1.35 (95 % CI, 1.26-1.44) at the 5th percentile (15.05 °C) of air temperature, and 1.06 (95 % CI, 1.02-1.10) at the 95th percentile (20.91 MJ/m2) of solar radiation, with the reference value set to their respective medians. ILI+ rates were not associated with the risk of hip fracture. In the stratified analyses, a stronger association between cold condition and hip fracture was observed in males. Based on the results, strategies for preventing hip fractures with a focus on behaviors under unfavorable weather conditions should be targeted at individuals at risk.

The Application of Contrast-Enhanced Ultrasound Galactography in Patients With Pathologic Nipple Discharge.

Twenty patients with pathologic nipple discharge underwent conventional galactography and contrast-enhanced ultrasound (CEUS) galactography. Images were reviewed for detection of suspicious lesions. Lesion localization information from CEUS galactography was recorded. We included 25 lesions from the 20 included patients. The pathological results revealed 13 intraductal papillomas. The detective rates of intraductal papilloma by conventional galactography and CEUS galactography were 92.31% and 100%, respectively. All the preoperative localizations of lesions from CEUS galactography were in accordance with the surgical detections. CEUS galactography is a highly effective tool for the detection of intraductal breast lesions, and it could provide accurate lesion localization information for an optimal surgical design.

Trio-based exome sequencing broaden the genetic spectrum in keratoconus.

Keratoconus (KC) is a complex corneal disorder with genetic factors involving in its pathogenesis. The genetic etiology of KC has not been fully elucidated. In this study, we aimed to expand the genetic spectrum in KC by trio-based exome sequencing. Trio-based exome sequencing was conducted in 20 patients with KC and their unaffected parents to broaden the genetic spectrum of the disease. With a series of filtering criteria, de novo, recessive homozygous, and compound heterozygous variants in candidate genes were identified, and the candidate genes were classified for further analysis. Finally, we identified 60 variants in 32 candidate genes through trio-based exome sequencing. Among the candidate genes, 10 genes (ARHGEF10, ARHGEF17, ASPM, FLNA, NDRG1, NEB, PLS3, STARD8, SYNE1, TTN) were classified as cytoskeleton-related genes, 4 genes (COL28A1, SDK1, STAB1, TENM2) were classified as cell adhesion-related genes, and 18 genes (APLP2, BCORL1, CCNB3, FOXN1, FUT8, GALNT10, HEPH, HHIP, HMGB3, HS6ST2, JADE3, KIAA0040, MCF2L, MYOF, QRICH2, RPS6KA6, SMARCA1, TNRC6A) were classified into other genes group. Additionally, the candidate rare deleterious variants in TTN were highly repeated in 25% trios. In conclusion, the study provided new insights into the genetic spectrum of KC which might underlie the genetic etiology for the disease. The findings would improve our understanding of pathogenesis in KC and provide critical clues to future functional validation.