Modified Transannular Patching Palliation versus Modified Blalock-Taussig-Thomas Shunt in Infants with Severe Tetralogy of Fallot with Diminutive Pulmonary Arteries.

OBJECTIVE: The purpose of this study was to compare pulmonary arterial (PA) growth and morbidity, mortality, reintervention and complete repair rates after modified transannular patching palliation (mTAP) versus modified Blalock-Taussig-Thomas shunt (mBTS) for palliation in infants with severe tetralogy of Fallot (TOF) with diminutive pulmonary arteries. METHODS: This was a retrospective case review study of 107 patients (64 males) with severe TOF who underwent staged repair with either mTAP (n = 55) or mBTS (n = 52) over an 8-year period. Procedure-related PA growth and morbidity, mortality, reintervention and complete repair rates were compared. RESULTS: Two deaths occurred in the mBTS group due to sudden cardiac arrest, and five patients needed reintervention after the mBTS procedure because of shunt thrombosis or stenosis. Postoperative complications of mBTS included sudden cardiac arrest, shunt thrombosis/stenosis, vocal cord palsy and diaphragmatic palsy. Unlike in the mBTS group, no death, severe complications or reintervention occurred in the mTAP group. Oxygen saturations post mTAP and mBTS were significantly higher, which improved from 67.73 ± 4.36% to 94.33 ± 2.19% in the mTAP group and from 68.24 ± 3.87% to 86.87 ± 3.38% in the mBTS group. The increase in oxygen saturation and pulmonary artery growth (from pre- to post palliation) was significantly better with mTAP than with mBTS palliation (p < 0.01). All 55 patients showed complete repair after mTAP, and the time from palliation to complete repair was significantly shorter in the mTAP group. CONCLUSIONS: In a severe form of TOF with the hypoplastic PA tree, mTAP seems to be a better strategy that is safe and better facilitates satisfactory pulmonary arterial growth until complete repair than the mBTS procedure.

Efficacy and safety comparison between axillary lymph node dissection with no axillary surgery in patients with sentinel node-positive breast cancer: a systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis aimed to study the evidence on the efficacy and safety of omitting axillary lymph node dissection (ALND) for patients with clinically node-negative but sentinel lymph node (SLN)-positive breast cancer using all the available evidence. METHODS: The Embase, Medline, and Cochrane Library databases were searched through February 25, 2023. Original trials that compared only the sentinel lymph node biopsy (SLNB) with ALND as the control group for patients with clinically node-negative but SLN-positive breast cancer were included. The primary outcomes were axillary recurrence rate, total recurrence rate, disease-free survival (DFS), and overall survival (OS). Meta-analyses were performed to compare the odds ratio (OR) in rates and the hazard ratios (HR) in time-to-event outcomes between both interventions. Based on different study designs, tools in the revised Cochrane risk of bias tool were used for randomized trials and the risk of bias in nonrandomized studies of interventions to assess the risk of bias for each included article. Funnel plots and Egger's test were used for the publication's bias assessment. RESULTS: In total, 30 reports from 26 studies were included in the systematic review (9 reports of RCTs, 21 reports of retrospective cohort studies). According to our analysis, omitting ALND in patients with clinically node-negative but SLN-positive breast cancer had a similar axillary recurrence rate (OR = 0.95, 95% confidence interval (CI): 0.76-1.20), DFS (HR = 1.02, 95% CI: 0.89-1.16), and OS (HR = 0.97, 95% CI: 0.92-1.03), but caused a significantly lower incidence of adverse events and benefited in locoregional recurrence rate (OR = 0.76, 95% CI: 0.59-0.97) compared with ALND. CONCLUSION: For patients with clinically node-negative but SLN-positive breast cancer (no matter the number of the positive SLN), this review showed that SLNB alone had a similar axillary recurrence rate, DFS, and OS, but caused a significantly lower incidence of adverse events and showed a benefit for the locoregional recurrence compared with ALND. An OS benefit was found in the Macro subset that used SLNB alone versus complete ALND. Therefore, omitting ALND is feasible in this setting. TRIAL REGISTRATION: CRD 42023397963.

Aortic regurgitation after closure of ventricular septal defect by transcatheter device: the long-term complication.

Ventricular septal defect is the most common type of CHD, and transcatheter ventricular septal defect closure has been shown to be an alternative to surgical closure with acceptable mortality and morbidity as well as encouraging results. Short-term and mid-term follow-ups have indicated the safety and efficacy of transcatheter closure, but long-term follow-up results were rare. In this report, we first found that aortic regurgitation occurred in patients 9-12 years following transcatheter closure and regurgitation were gradually increased. The findings indicate that the long-term outcome of transcatheter closure of ventricular septal defect may not be as satisfied as expected.

Epitaxial Growth of 6 in. Single-Crystalline Graphene on a Cu/Ni (111) Film at 750 °C via Chemical Vapor Deposition.

The future electronic application of graphene highly relies on the production of large-area high-quality single-crystal graphene. However, the growth of single-crystal graphene on different substrates via either single nucleation or seamless stitching is carried out at a temperature of 1000 °C or higher. The usage of this high temperature generates a variety of problems, including complexity of operation, higher contamination, metal evaporation, and wrinkles owing to the mismatch of thermal expansion coefficients between the substrate and graphene. Here, a new approach for the fabrication of ultraflat single-crystal graphene using Cu/Ni (111)/sapphire wafers at lower temperature is reported. It is found that the temperature of epitaxial growth of graphene using Cu/Ni (111) can be reduced to 750 °C, much lower than that of earlier reports on catalytic surfaces. Devices made of graphene grown at 750 °C have a carrier mobility up to ≈9700 cm2 V-1 s-1 at room temperature. This work shines light on a way toward a much lower temperature growth of high-quality graphene in single crystallinity, which could benefit future electronic applications.

miR-205-5p suppresses pulmonary vascular smooth muscle cell proliferation by targeting MICAL2-mediated Erk1/2 signaling.

Pulmonary arterial hypertension (PAH) is a devastating and fatal vascular disease for which currently there is no satisfying therapy available. Excessive cell proliferation of pulmonary arterial smooth muscle cells (PASMCs) contributes significantly to PAH pathogenesis. In this study, we found that miR-205-5p was lowly expressed in hypoxia-induced PAH mouse model and hypoxia-treated PASMCs. Restoration of miR-205-5p suppressed PASMCs proliferation. In contrast, molecule interacting with CasL 2 (MICAL2) was highly expressed in hypoxia-induced PAH mouse model and hypoxia-treated PASMCs. Overexpression of MICAL2 promoted cell proliferation. Furthermore, miR-205-5p inhibited MICAL2 expression levels by targeting the MICAL2 3' untranslated region. In addition, MICAL2 activated ERK1/2 signaling in PASMCs and ERK1/2 inhibitor blocked MICAL2-mediated-promotion effect on PASMCs proliferation. These results demonstrated that miR-205-5p suppressed PASMCs proliferation by targeting MICAL2, which activated ERK1/2 signaling. Therefore, miR-205-5p/MICAL2/Erk1/2 may serve as an ideal therapeutic target to PAH treatment.

Conformational Transitions of Phase-Separated Binary Molecules Assisted by Surface Dehalogenation.

Molecular devices have become an emergent branch of nanoscience and technology beyond traditional silicon-based electronic devices. The properties of these devices are intimately related to the molecular conformation and packing. In this article, three different conformations of melamine molecules are observed on Au(111), and a transition from the lying-down to standing-up phase with long-range order is realized in melamine chains with the assistance of hexabromobenzene (HBB). We argue that it is the expanding of HBB domains from hexagonal to the dimer phase due to surface dehalogenation that facilitates the dehydrogenation of melamine to form a standing-up conformation. Similar transitions are also accomplished on the Ag(111) surface. Our results provide an effective way to achieve standing-up molecular arrays with long-range order on relatively less active metals. This may have significant implications in fabricating organic thin film transistors.

PlaMoM: a comprehensive database compiles plant mobile macromolecules.

In plants, various phloem-mobile macromolecules including noncoding RNAs, mRNAs and proteins are suggested to act as important long-distance signals in regulating crucial physiological and morphological transition processes such as flowering, plant growth and stress responses. Given recent advances in high-throughput sequencing technologies, numerous mobile macromolecules have been identified in diverse plant species from different plant families. However, most of the identified mobile macromolecules are not annotated in current versions of species-specific databases and are only available as non-searchable datasheets. To facilitate study of the mobile signaling macromolecules, we compiled the PlaMoM (Plant Mobile Macromolecules) database, a resource that provides convenient and interactive search tools allowing users to retrieve, to analyze and also to predict mobile RNAs/proteins. Each entry in the PlaMoM contains detailed information such as nucleotide/amino acid sequences, ortholog partners, related experiments, gene functions and literature. For the model plant Arabidopsis thaliana, protein-protein interactions of mobile transcripts are presented as interactive molecular networks. Furthermore, PlaMoM provides a built-in tool to identify potential RNA mobility signals such as tRNA-like structures. The current version of PlaMoM compiles a total of 17 991 mobile macromolecules from 14 plant species/ecotypes from published data and literature. PlaMoM is available at http://www.systembioinfo.org/plamom/.

Lentivirus-mediated down-regulation of CK2α inhibits proliferation and induces apoptosis of malignant lymphoma and leukemia cells.

Casein kinase II subunit alpha (CK2α) is highly expressed in many malignant tumor tissues, including lymphomas and leukemia. To investigate the role of CK2α in cell proliferation and apoptosis of malignant lymphomas and leukemia, 2 lymphoma cell lines and one leukemia cell line were infected with CK2α shRNA lentivirus or negative control shRNA lentivirus, and stably infected cell lines were established. Real-time PCR and Western blot results showed that the mRNA and protein levels of CK2α were significantly reduced in CK2α knockdown cells. The tetrazolium-based colorimetric (MTT) assay found that down-regulation of CK2α inhibited the proliferation of these cells. Flow cytometry analysis showed that inhibition of CK2α induced cell cycle arrest and apoptosis of lymphoma and leukemia cells. In accordance with these, down-regulation of CK2α also reduced the protein levels of proliferating cell nuclear antigen (PCNA), cyclinD1, and bcl-2, and increased the protein expression of bax, cleaved caspase-3, cleaved caspase-9, and cleaved poly(ADP ribose) polymerase (PARP). Moreover, knockdown of CK2α impeded the growth of xenograft tumors in vivo. In summary, our study revealed that CK2α may contribute to the development of malignant lymphoma and leukemia, and serve as the therapeutic target of these malignant tumors.

Knockdown of long non-coding RNA TP73-AS1 suppresses triple negative breast cancer cell vasculogenic mimicry by targeting miR-490-3p/TWIST1 axis.

Triple negative breast cancer (TNBC) is among the most clinically aggressive subtypes of breast cancer. Despite the availability of new drugs, patients suffering TNBC bear disheartening prognosis. Vasculogenic mimicry (VM) is a malignant tumor specific non-endothelial vascular network, which provide oxygen and nutrients to tumor cells and facilitate tumor progression. Therefore targeting TNBC VM formation may contribute to tumor treatment. In this study, we found that long non-coding RNA TP73 antisense RNA 1 (TP73-AS1) was upregulated in VM positive TNBC tissues. Knockdown of TP73-AS1 suppressed TNBC cell line MDA-MB-231 cell VM formation in vitro. In addition, RNA immunoprecipitation assay and dual luciferase reporter assay showed that TP73-AS1 bound to miR-490-3p in a sequence-specific manner. miR-490-3p was downregulated in VM positive tissues and was involved in TP73-AS1-mediated MDA-MB-231 cell VM formation. Furthermore, TWIST1 was a target of miR-490-3p and participated in TP73-AS1/miR-490-3p-modulated MDA-MB-231 cell VM formation. Findings in this study may provide insight in TNBC management.

A Novel Displacement and Tilt Detection Method Using Passive UHF RFID Technology.

The displacement and tilt angle of an object are useful information for wireless monitoring applications. In this paper, a low-cost detection method based on passive radio frequency identification (RFID) technology is proposed. This method uses a standard ultrahigh-frequency (UHF) RFID reader to measure the phase variation of the tag response and detect the displacement and tilt angle of RFID tags attached to the targeted object. An accurate displacement result can be detected by the RFID system with a linearly polarized (LP) reader antenna. Based on the displacement results, an accurate tilt angle can also be detected by the RFID system with a circularly polarized (CP) reader antenna, which has been proved to have a linear relationship with the phase parameter of the tag’s backscattered wave. As far as accuracy is concerned, the mean absolute error (MAE) of displacement is less than 2 mm and the MAE of the tilt angle is less than 2.5° for an RFID system with 500 mm working range.

Induced sputum deposition improves diagnostic yields of pulmonary alveolar proteinosis: A clinicopathological and methodological study of 17 cases.

Pulmonary alveolar proteinosis (PAP) is a rare diffuse lung disease characterized by the accumulation of intra-alveolar lipoprotein-like surfactants. Lung core biopsy and bronchoalveolar lavage (BAL) fluid are currently the two major sources of sampling for diagnosis. In the present study, we assessed the value of induced sputum in diagnosing PAP by transmission electron microscopy and examined the PAP 2-year death rate in Asians. Transmission electron microscopy was performed on the samples from 17 patients with PAP, 13 patients with inflammatory lung diseases, and 13 healthy adults. The PAP patients were followed up for 3-156 months, and inflammatory lung diseases patients or healthy adults for 12-36 months. The ultrastructural features including diagnostic lamellar bodies of induced sputum deposition (ISD) samples were similar to that of the BAL fluid sediment. However, the rates of lamellar bodies were 73.7% in the ISD group, significantly higher than the spontaneous sputum deposition (SSD) group (42.1%, P < .0487) and similar to the BAL sediment (76.2%) and the lung biopsy (54.5%) groups. The overall 2-year death rate of our PAP patients was 17.6% (3/17), not statistically different from the healthy adults and patients with inflammatory diseases (0/13, P = .237 for both). ISD may be the preferred non-invasive sampling method for diagnosing PAP by electronic microscopy because of the higher diagnostic yield than SSD. The diagnostic yields of this noninvasive method were similar to that of lung core biopsy and BAL.

Metabolomics and Its Application in the Development of Discovering Biomarkers for Osteoporosis Research.

Osteoporosis is a progressive skeletal disorder characterized by low bone mass and increased risk of fracture in later life. The incidence and costs associated with treating osteoporosis cause heavy socio-economic burden. Currently, the diagnosis of osteoporosis mainly depends on bone mineral density and bone turnover markers. However, these indexes are not sensitive and accurate enough to reflect the osteoporosis progression. Metabolomics offers the potential for a holistic approach for clinical diagnoses and treatment, as well as understanding of the pathological mechanism of osteoporosis. In this review, we firstly describe the study subjects of osteoporosis and bio-sample preparation procedures for different analytic purposes, followed by illustrating the biomarkers with potentially predictive, diagnosis and pharmaceutical values when applied in osteoporosis research. Then, we summarize the published metabolic pathways related to osteoporosis. Furthermore, we discuss the importance of chronological data and combination of multi-omics in fully understanding osteoporosis. The application of metabolomics in osteoporosis could provide researchers the opportunity to gain new insight into the metabolic profiling and pathophysiological mechanisms. However, there is still much to be done to validate the potential biomarkers responsible for the progression of osteoporosis and there are still many details needed to be further elucidated.

Molecular Insight into Gut Microbiota and Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a systemic, inflammatory, and autoimmune disorder. Gut microbiota play an important role in the etiology of RA. With the considerable progress made in next-generation sequencing techniques, the identified gut microbiota difference between RA patients and healthy individuals provides an updated overview of the association between gut microbiota and RA. We reviewed the reported correlation and underlying molecular mechanisms among gut microbiota, the immune system, and RA. It has become known that gut microbiota contribute to the pathogenesis of RA via multiple molecular mechanisms. The progressive understanding of the dynamic interaction between gut microbiota and their host will help in establishing a highly individualized management for each RA patient, and achieve a better efficacy in clinical practice, or even discovering new drugs for RA.

Predicting protein functions using incomplete hierarchical labels.

BACKGROUND: Protein function prediction is to assign biological or biochemical functions to proteins, and it is a challenging computational problem characterized by several factors: (1) the number of function labels (annotations) is large; (2) a protein may be associated with multiple labels; (3) the function labels are structured in a hierarchy; and (4) the labels are incomplete. Current predictive models often assume that the labels of the labeled proteins are complete, i.e. no label is missing. But in real scenarios, we may be aware of only some hierarchical labels of a protein, and we may not know whether additional ones are actually present. The scenario of incomplete hierarchical labels, a challenging and practical problem, is seldom studied in protein function prediction. RESULTS: In this paper, we propose an algorithm to Predict protein functions using Incomplete hierarchical LabeLs (PILL in short). PILL takes into account the hierarchical and the flat taxonomy similarity between function labels, and defines a Combined Similarity (ComSim) to measure the correlation between labels. PILL estimates the missing labels for a protein based on ComSim and the known labels of the protein, and uses a regularization to exploit the interactions between proteins for function prediction. PILL is shown to outperform other related techniques in replenishing the missing labels and in predicting the functions of completely unlabeled proteins on publicly available PPI datasets annotated with MIPS Functional Catalogue and Gene Ontology labels. CONCLUSION: The empirical study shows that it is important to consider the incomplete annotation for protein function prediction. The proposed method (PILL) can serve as a valuable tool for protein function prediction using incomplete labels. The Matlab code of PILL is available upon request.

Predicting protein function via downward random walks on a gene ontology.

BACKGROUND: High-throughput bio-techniques accumulate ever-increasing amount of genomic and proteomic data. These data are far from being functionally characterized, despite the advances in gene (or gene's product proteins) functional annotations. Due to experimental techniques and to the research bias in biology, the regularly updated functional annotation databases, i.e., the Gene Ontology (GO), are far from being complete. Given the importance of protein functions for biological studies and drug design, proteins should be more comprehensively and precisely annotated. RESULTS: We proposed downward Random Walks (dRW) to predict missing (or new) functions of partially annotated proteins. Particularly, we apply downward random walks with restart on the GO directed acyclic graph, along with the available functions of a protein, to estimate the probability of missing functions. To further boost the prediction accuracy, we extend dRW to dRW-kNN. dRW-kNN computes the semantic similarity between proteins based on the functional annotations of proteins; it then predicts functions based on the functions estimated by dRW, together with the functions associated with the k nearest proteins. Our proposed models can predict two kinds of missing functions: (i) the ones that are missing for a protein but associated with other proteins of interest; (ii) the ones that are not available for any protein of interest, but exist in the GO hierarchy. Experimental results on the proteins of Yeast and Human show that dRW and dRW-kNN can replenish functions more accurately than other related approaches, especially for sparse functions associated with no more than 10 proteins. CONCLUSION: The empirical study shows that the semantic similarity between GO terms and the ontology hierarchy play important roles in predicting protein function. The proposed dRW and dRW-kNN can serve as tools for replenishing functions of partially annotated proteins.

CoagVDb: a comprehensive database for coagulation factors and their associated SAPs.

The current state of the art in medical genetics is to identify and classify the functional (deleterious) or non-functional (neutral) single amino acid substitutions (SAPs), also known as non-synonymous SNPs (nsSNPs). The primary goal is to elucidate the mechanisms through which functional SAPs exert their effects, and ultimately interrogating this information for association with complex phenotypes. This work focuses on coagulation factors involved in the coagulation cascade pathway which plays a vital role in the maintenance of homeostasis in the human system. We developed an integrated coagulation variation database, CoagVDb, which makes use of the biological information from various public databases such as NCBI, OMIM, UniProt, PDB and SAPs (rsIDs/variant). CoagVDb enriched with computational prediction scores classify SAPs as either deleterious or tolerated. Also, various other properties are incorporated such as amino acid composition, secondary structure elements, solvent accessibility, ordered/disordered regions, conservation, and the presence of disulfide bonds. This specialized database provides integration of various prediction scores from different computational methods along with gene, protein, and disease information. We hope our database will act as a useful reference resource for hematologists to reveal protein structure-function relationship and disease genotype-phenotype correlation.

Surgical correction of anomalous origin of one pulmonary artery without grafts in infants.

OBJECTIVE: To review the experiences in repairing the anomalous origin of one pulmonary artery in infants. METHODS: From March 2005 to May 2010, 11 infants diagnosed with anomalous origin of one pulmonary artery underwent surgical treatment. Their mean age was 12.7 months (two months to three years), and their mean body weight was 7.1 kg (4 to 13 kg). Seven patients had anomalous origin of the right pulmonary artery, and four patients had anomalous origin of the left pulmonary artery. All 11 patients had an intracardiac anomaly or vascular malformations as well as pulmonary hypertension. A median sternotomy and cardiopulmonary bypass (CPB) were used in all 11 patients. The mean follow-up was 20.5 months (6 to 60 months). RESULTS: The operation time was 169 to 293 min (231 ± 55 min), the CPB time was 87 to 210 min (138 ± 47 min), and the aortic cross-clamp time was 45 to 133 min (86 ± 28 min). There was one hospital death (mortality 9%) in a patient with tetralogy of Fallot who had low cardiac output after the operation. In all cases, there was no application of artificial or homologous grafts. All surviving patients had satisfactory early to midterm results except for one patient with mild pulmonary stenosis. CONCLUSION: The surgical correction of anomalous origin of one pulmonary artery without artificial or homologous grafts has satisfactory early to midterm results in infants.

[Effect of Paidu Baoshen Pill on renal fibrosis in 5/6 nephrectomized rats].

OBJECTIVE: To observe the anti-renal fibrosis effect of Paidu Baoshen Pill (PBP) on 5/6 nephrectomized rats and to explore its mechanism. METHODS: Totally 50 SD male healthy rats were randomly divided into the normal control group (n = 10), the sham-operation group (n = 10), and the nephrectomy model group (n = 30) according to the proportion of 1:1:3. Rats in the sham-operation group had their renal capsule isolated without nephrectomy. Rats in the nephrectomy model group had their kidneys 5/6 nephrectomized. Then 24 h urine was collected and 24 h urinary protein (24 h UP) detected. Serum blood urea nitrogen (BUN) and serum creatitine (SCr) were also tested. According to the SCr level 30 rats of the model group were further randomly divided into the model group, the PBP group, and the Niaoduqing Granule (NG) group, 10 in each group. Rats in the PBP group and the NG group were respectively administered with PBP (at the daily dose of 1.0 g/kg) and NG (at the daily dose of 3.33 g/kg) by gastrogavage (they were dissolved in distilled water). At the same time, 2 mL distilled water was administered by gastrogavage to rats in the normal control group, the sham-operation group, and the nephrectomy model group, once daily for 4 successive weeks. Mental conditions, activities, hair color, shape of stool, and the body weight were observed during administration. After 4 weeks, urine was collected to detect 24 h UP. Blood was sampled to detect SCr, BUN, transforming growth factor ß1 (TGF-ß1), type III procollagen (PC III), collagen type IV (Col IV), laminin (LN), and fibronectin (FN). After rats were killed, their left remnant renal tissues were collected for pathological examinations. The protein expression quantity of TGF-ß1 and FN was detected by immunohistochemical method. mRNA expression levels of TGF-ß1 and FN were detected using real time fluorescent quantitative PCR. RESULTS: There was no statistical difference in the above indices between the normal control group and the sham-operation group (P > 0.05). Compared with the sham-operation group, rats' general condition was poorer in the model group, their body weight grew slower, and 24 h UP increased; serum levels of BUN, SCr, TGF-ß1, PC III, Col IV, LN, and FN increased; the residual renal pathological lesion was serious; expression levels of TGF-ß1, TGF-ß1, mRNA, FN, and FN mRNA increased in the renal tissue (all P < 0.01). Compared with the model group, rats' general condition was better, their body weight grew faster, 24 h UP reduced (P < 0.05), blood levels of BUN and SCr decreased significantly (P < 0.01), serum levels of TGF-ß1, PC III, CoL IV, LN, and FN decreased (P < 0.05, P < 0.01); the residual renal pathological lesion was attenuated in the PBP group and the NG group; expression levels of TGF-ß1, TGF-ß1, mRNA, FN, and FN mRNA decreased (P < 0.01). Compared with the NG group, blood levels of SCr and FN, and expression levels of FN and FN mRNA decreased more in the PBP group (P < 0.05). CONCLUSIONS: PBP had the effect of anti-renal fibro- sis in 5/6 nephrectomized rats. Down-regulating expression levels of TGF-ß1, and FN from gene transcription and protein translation levels might be one of its mechanisms.

Extrapolating the effect of deleterious nsSNPs in the binding adaptability of flavopiridol with CDK7 protein: a molecular dynamics approach.

BACKGROUND: Recent reports suggest the role of nonsynonymous single nucleotide polymorphisms (nsSNPs) in cyclin-dependent kinase 7 (CDK7) gene associated with defect in the DNA repair mechanism that may contribute to cancer risk. Among the various inhibitors developed so far, flavopiridol proved to be a potential antitumor drug in the phase-III clinical trial for chronic lymphocytic leukemia. Here, we described a theoretical assessment for the discovery of new drugs or drug targets in CDK7 protein owing to the changes caused by deleterious nsSNPs. METHODS: Three nsSNPs (I63R, H135R, and T285M) were predicted to have functional impact on protein function by SIFT, PolyPhen2, I-Mutant3, PANTHER, SNPs&GO, PhD-SNP, and screening for non-acceptable polymorphisms (SNAP). Furthermore, we analyzed the native and proposed mutant models in atomic level 10 ns simulation using the molecular dynamics (MD) approach. Finally, with the aid of Autodock 4.0 and PatchDock, we analyzed the binding efficacy of flavopiridol with CDK7 protein with respect to the deleterious mutations. RESULTS: By comparing the results of all seven prediction tools, three nsSNPs (I63R, H135R, and T285M) were predicted to have functional impact on the protein function. The results of protein stability analysis inferred that I63R and H135R exhibited less deviation in root mean square deviation in comparison with the native and T285M protein. The flexibility of all the three mutant models of CDK7 protein is diverse in comparison with the native protein. Following to that, docking study revealed the change in the active site residues and decrease in the binding affinity of flavopiridol with mutant proteins. CONCLUSION: This theoretical approach is entirely based on computational methods, which has the ability to identify the disease-related SNPs in complex disorders by contrasting their costs and capabilities with those of the experimental methods. The identification of disease related SNPs by computational methods has the potential to create personalized tools for the diagnosis, prognosis, and treatment of diseases. LAY ABSTRACT: Cell cycle regulatory protein, CDK7, is linked with DNA repair mechanism which can contribute to cancer risk. The main aim of this study is to extrapolate the relationship between the nsSNPs and their effects in drug-binding capability. In this work, we propose a new methodology which (1) efficiently identified the deleterious nsSNPs that tend to have functional effect on protein function upon mutation by computational tools, (2) analyze d the native protein and proposed mutant models in atomic level using MD approach, and (3) investigated the protein-ligand interactions to analyze the binding ability by docking analysis. This theoretical approach is entirely based on computational methods, which has the ability to identify the disease-related SNPs in complex disorders by contrasting their costs and capabilities with those of the experimental methods. Overall, this approach has the potential to create personalized tools for the diagnosis, prognosis, and treatment of diseases.