DeepKEGG: a multi-omics data integration framework with biological insights for cancer recurrence prediction and biomarker discovery.

Deep learning-based multi-omics data integration methods have the capability to reveal the mechanisms of cancer development, discover cancer biomarkers and identify pathogenic targets. However, current methods ignore the potential correlations between samples in integrating multi-omics data. In addition, providing accurate biological explanations still poses significant challenges due to the complexity of deep learning models. Therefore, there is an urgent need for a deep learning-based multi-omics integration method to explore the potential correlations between samples and provide model interpretability. Herein, we propose a novel interpretable multi-omics data integration method (DeepKEGG) for cancer recurrence prediction and biomarker discovery. In DeepKEGG, a biological hierarchical module is designed for local connections of neuron nodes and model interpretability based on the biological relationship between genes/miRNAs and pathways. In addition, a pathway self-attention module is constructed to explore the correlation between different samples and generate the potential pathway feature representation for enhancing the prediction performance of the model. Lastly, an attribution-based feature importance calculation method is utilized to discover biomarkers related to cancer recurrence and provide a biological interpretation of the model. Experimental results demonstrate that DeepKEGG outperforms other state-of-the-art methods in 5-fold cross validation. Furthermore, case studies also indicate that DeepKEGG serves as an effective tool for biomarker discovery. The code is available at https://github.com/lanbiolab/DeepKEGG.

IBPGNET: lung adenocarcinoma recurrence prediction based on neural network interpretability.

Lung adenocarcinoma (LUAD) is the most common histologic subtype of lung cancer. Early-stage patients have a 30-50% probability of metastatic recurrence after surgical treatment. Here, we propose a new computational framework, Interpretable Biological Pathway Graph Neural Networks (IBPGNET), based on pathway hierarchy relationships to predict LUAD recurrence and explore the internal regulatory mechanisms of LUAD. IBPGNET can integrate different omics data efficiently and provide global interpretability. In addition, our experimental results show that IBPGNET outperforms other classification methods in 5-fold cross-validation. IBPGNET identified PSMC1 and PSMD11 as genes associated with LUAD recurrence, and their expression levels were significantly higher in LUAD cells than in normal cells. The knockdown of PSMC1 and PSMD11 in LUAD cells increased their sensitivity to afatinib and decreased cell migration, invasion and proliferation. In addition, the cells showed significantly lower EGFR expression, indicating that PSMC1 and PSMD11 may mediate therapeutic sensitivity through EGFR expression.

Desmoplastic fibroma in a child: a 9-year follow-up case report.

BACKGROUND: Desmoplastic fibroma is an extremely rare primary bone tumor. Its characteristic features include bone destruction accompanied by the formation of soft tissue masses. This condition predominantly affects individuals under the age of 30. Since its histology is similar to desmoid-type fibromatosis, an accurate diagnosis before operation is difficult. Desmoplastic fibroma is resistant to chemotherapy, and the efficacy of radiotherapy is uncertain. Surgical excision is preferred for treatment, but it entails high recurrence. Further, skeletal reconstruction post-surgery is challenging, especially in pediatric cases. CASE PRESENTATION: Nine years ago, a 14-year-old male patient presented with a 4-year history of progressive pain in his left wrist. Initially diagnosed as fibrous dysplasia by needle biopsy, the patient underwent tumor resection followed by free vascularized fibular proximal epiphyseal transfer for wrist reconstruction. However, a histological examination confirmed a diagnosis of desmoplastic fibroma. The patient achieved bone union and experienced a recurrence in the ipsilateral ulna 5 years later, accompanied by a wrist deformity. He underwent a second tumor resection and wrist arthrodesis in a single stage. The most recent annual follow-up was in September 2023; the patient had no recurrence and was satisfied with the surgery. CONCLUSIONS: Desmoplastic fibroma is difficult to diagnose and treat, and reconstruction surgery after tumor resection is challenging. Close follow-up by experienced surgeons may be beneficial for prognosis.

Adult-onset congenital cholesteatoma in the hypotympanum initially presenting as Bell's palsy: A case report.

INTRODUCTION: Cholesteatoma is a rare disease characterized by the accumulation of keratinized squamous epithelial cells in the middle ear or mastoid cavity. Vertigo and facial palsy, which are rare complications, may indicate erosion into the semicircular canals or the fallopian canal. PATIENT CONCERNS: A 40-year-old woman presented to our clinic with progressive right-sided hearing loss over 5 years (primary concern). Approximately 10 years ago, the patient had developed acute right-sided facial weakness with no additional symptoms. A neurologist at another hospital had diagnosed her condition as Bell's palsy and treated it accordingly. DIAGNOSIS: Adult-onset congenital cholesteatoma in the hypotympanum. INTERVENTION: Combined endoscopic and microscopic removal of the cholesteatoma. OUTCOMES: Physical examination revealed slight improvement in right-sided peripheral facial palsy. LESSON: Routine eardrum examination is recommended for patients presenting with isolated peripheral facial palsy. If necessary, a patient should be referred to an otologist for further evaluation and treatment.

Natural Herbal Compounds Exerting an Antidepressant Effect through Hypothalamic-Pituitary-Adrenal Axis Regulation.

Depression is a common mental illness that damages the life and health of patients and causes economic burden, and HPA (hypothalamic-pituitary-adrenal) axis dysfunction is considered to be one of the important factors leading to depression. In this case, it is essential to explore possible treatment methods by using natural compounds with HPA axis regulating and antidepressant effects. However, no one has reviewed it so far. Therefore, the purpose of this review is to systematically sort out the related natural products that play an antidepressant role by regulating the function of the HPA axis. Natural products are divided into flavonoids, polyphenols, terpenoids, saponins, polysaccharides and so on according to their chemical structures, which play a variety of biological activities such as regulating the HPA axis, anti-inflammation and neuroprotection. These effects may provide a useful reference for the potential treatment of depression so as to develop new antidepressants.

Overexpression SPRY2 Suppresses Esophageal Squamous Cell Carcinoma Progression Via Inactivation of ERK/AKT Signaling / La Sobreexpresión SPRY2 Suprime la Evolución del Carcinoma de Células Escamosas de Esófago Mediante la Inactivación de la Señalización ERK/AKT

SUMMARY: Esophageal cancer is one of the most aggressive gastrointestinal cancers. Invasion and metastasis are the main causes of poor prognosis of esophageal cancer. SPRY2 has been reported to exert promoting effects in human cancers, which controls signal pathways including PI3K/AKT and MAPKs. However, the expression of SPRY2 in esophageal squamous cell carcinoma (ESCC) and its underlying mechanism remain unclear. In the present study, we aimed to investigate the detailed role of SPRY2 in the regulation of cell proliferation, invasion and ERK/AKT signaling pathway in ESCC. It was identified that the expression level of SPRY2 in ESCC was remarkably decreased compared with normal tissues, and it was related to clinicopathologic features and prognosis ESCC patients. The upregulation of SPRY2 expression notably inhibited the proliferation, migration and invasion of Eca-109 cells. In addition, the activity of ERK /AKT signaling was also suppressed by the SPRY2 upregulation in Eca-109 cells. Our study suggests that overexpression of SPRY2 suppress cancer cell proliferation and invasion of by through suppression of the ERK/AKT signaling pathways in ESCC. Therefore, SPRY2 may be a promising prognostic marker and therapeutic target for ESCC.

El cáncer de esófago es uno de los cánceres gastrointestinales más agresivos. La invasión y la metástasis son las principales causas de mal pronóstico del cáncer de esófago. Se ha informado que SPRY2 ejerce efectos promotores en los cánceres humanos, que controla las vías de señales, incluidas PI3K/AKT y MAPK. Sin embargo, la expresión de SPRY2 en el carcinoma de células escamosas de esófago (ESCC) y su mecanismo subyacente aún no están claros. En el presente estudio, nuestro objetivo fue investigar el papel detallado de SPRY2 en la regulación de la proliferación celular, la invasión y la vía de señalización ERK/AKT en ESCC. Se identificó que el nivel de expresión de SPRY2 en ESCC estaba notablemente disminuido en comparación con los tejidos normales, y estaba relacionado con las características clínico-patológicas y el pronóstico de los pacientes con ESCC. La regulación positiva de la expresión de SPRY2 inhibió notablemente la proliferación, migración e invasión de células Eca-109. Además, la actividad de la señalización de ERK/AKT también fue suprimida por la regulación positiva de SPRY2 en las células Eca-109. Nuestro estudio sugiere que la sobreexpresión de SPRY2 suprime la proliferación y la invasión de células cancerosas mediante la supresión de las vías de señalización ERK/AKT en ESCC. Por lo tanto, SPRY2 puede ser un marcador de pronóstico prometedor y un objetivo terapéutico para la ESCC.

FAPI PET Missed Widespread Bone Marrow Metastases From Follicular Thyroid Cancer That Were Detected by FDG PET.

ABSTRACT: A 62-year-old woman with follicular thyroid cancer who had received total thyroidectomy and multiple rounds of radioactive iodine therapy underwent both 18 F-FDG and 18 F-FAPI PET/CT. 18 F-FAPI PET failed to reveal widespread bone marrow metastases that were clear visualized on 18 F-FDG PET. This case highlights that FAPI PET may not be used to describe bone metastases in detail in follicular thyroid cancer patients, as it is not a sensitive method to detect bone marrow metastases.

Improving gut functions and egg nutrition with stevia residue in laying hens.

This study aimed to investigate the effect of stevia residue (STER) on the production performance, egg quality and nutrition, antioxidant ability, immune responses, gut morphology and microbiota of laying hens during the peak laying period. A total of 270 Yikoujingfen NO. 8 laying hens (35 wk of age) were randomly divided into 5 treatments. The control group fed a basal diet and groups supplemented with 2, 4, 6, and 8% STER. The results showed that STER significantly increased egg production, the content of amino acids (alanine, proline, valine, ornithine, asparagine, aspartic acid, and cysteine) in egg whites, and decreased the yolk color (P < 0.05). Additionally, STER significantly increased acetate, HOMOγ linolenic acid and cis-13, 16-docosadienoic acid levels in egg yolk (P < 0.05). IL-2, IL-4, and IL-10 levels in serum significantly increased by STER (P < 0.05), while IL-1ß significantly decreased (P < 0.05). STER also increased total antioxidant activity (T-AOC) in the liver and estradiol level in the oviduct (P < 0.05), but decreased the cortisol level in the oviduct (P < 0.05). For the intestinal morphology, the jejunal villus height and crypt-to-villus (V:C) significantly increased by STER (P < 0.05). STER increased the relative abundance of Actinobacteriota (P < 0.05), while deceased Proteobacteria, Desulfobacterota, and Synergistota (P < 0.05). In conclusion, STER improved egg production, quality and nutrition, improved the immune responses, antioxidant capabilities, estrogen level, gut morphology, and increased the relative abundance of beneficial bacteria while decreased the harmful bacteria. Among all treatments, 4 and 6% STER supplementation yielded the most favorable results in terms of enhancing production performance, egg nutrition, gut health, and immune capabilities in laying hens.

Mycobacterial Infection in Recalcitrant Otomastoiditis: A Case Series and Literature Review.

Otomastoiditis caused by mycobacterial infections is uncommon and recalcitrant. Its clinical presentations, sometimes similar to those of common chronic suppurative otitis media, make diagnosis difficult. This retrospective study analyzed the clinical features, treatment course, and therapeutic outcomes of patients with mycobacterial otomastoiditis. The cases of six patients diagnosed with mycobacterial otomastoiditis or suspected mycobacterial infection between January 2007 and January 2019 in a single tertiary medical center in Taiwan were investigated. Information about predisposing factors, clinical features, culture reports, histopathology, treatment course, and outcomes were collected and analyzed. Relevant literature available in English was also reviewed. One patient was infected with tuberculous mycobacteria, two with suspected tuberculous mycobacteria, and three with nontuberculous mycobacteria. All six patients responded poorly to empiric antibiotic therapy, and diagnosis was not possible at their previous clinics. Five patients underwent tympanomastoidectomies; one was administered antimycobacterial medication without undergoing surgery. Mycobacterial infection was confirmed from a tissue culture or from the histopathology of the specimen, but in two patients, no definitive evidence of tuberculosis was found. Antimycobacterial medication was administered based on clinical suspicion, and improvement was noted. With appropriate therapy, all patients recovered, and no sequelae were observed after treatment. If empiric antibiotic therapy cannot achieve acceptable results, atypical infections, such as mycobacteria, should be considered. Antimycobacterial medication could be administered under clinical suspicion, serving as a diagnosis ex juvantibus. Surgical intervention might help reduce the bacterial load and obtain specimens for accurate diagnosis, but this may be unnecessary if appropriate antimycobacterial medication results in improvement. Early diagnosis and treatment can prevent complications in patients with recalcitrant otomastoiditis.

Primary versus salvage intratympanic steroid treatment for idiopathic sudden sensorineural hearing loss.

Objective: The objective of this research is to compare primary and salvage intratympanic (IT) steroid treatments in terms of hearing outcomes in patients with idiopathic sudden sensorineural hearing loss (ISSNHL). Methods: The patients were randomized into two (primary and salvage) groups. Both groups received systemic steroid treatment for 2 weeks. The primary group also received IT dexamethasone injection three times during the treatment period, whereas the salvage group received IT dexamethasone injection only if no or slight recovery was noted at the 2-week follow-up. If needed, salvage steroid injection was administered three times during the following 2 weeks. Hearing recovery was analyzed according to the modified American Academy of Otolaryngology-Head and Neck Surgery criteria. Results: The degrees of hearing improvement at the 3-month follow-up were similar in the two groups. Compared with baseline, the pure-tone average values and speech discrimination scores improved by 38.45 ± 21.95 dB HL and 34.32% ± 30.55%, respectively, in the primary group and 36.80 ± 22.33 dB HL and 31.87% ± 27.88%, respectively, in the salvage group (p = .762 and .659, respectively). In addition, the complete or partial hearing recovery rates were also similar in the primary and salvage groups (67.7% vs. 73.3%, respectively; p = .780). In the salvage group, 18 patients required no IT steroid injection because they recovered after systemic steroid treatment. Conclusion: Primary and salvage IT steroid treatments for ISSNHL led to similar outcomes. In summary, salvage IT steroid injection is recommended for patients with ISSNHL patients to prevent unnecessary IT injection. Level of evidence: 2.

Enzyme-less nanopore detection of post-translational modifications within long polypeptides.

Means to analyse cellular proteins and their millions of variants at the single-molecule level would uncover substantial information previously unknown to biology. Nanopore technology, which underpins long-read DNA and RNA sequencing, holds potential for full-length proteoform identification. We use electro-osmosis in an engineered charge-selective nanopore for the non-enzymatic capture, unfolding and translocation of individual polypeptides of more than 1,200 residues. Unlabelled thioredoxin polyproteins undergo transport through the nanopore, with directional co-translocational unfolding occurring unit by unit from either the C or N terminus. Chaotropic reagents at non-denaturing concentrations accelerate the analysis. By monitoring the ionic current flowing through the nanopore, we locate post-translational modifications deep within the polypeptide chains, laying the groundwork for compiling inventories of the proteoforms in cells and tissues.

A Gene Correlation Measurement Method for Spatial Transcriptome Data Based on Partitioning and Distribution.

Spatial transcriptome (ST) technology provides both the spatial location and transcriptional profile of spots, as well as tissue images. ST data can be utilized to construct gene regulatory networks, which can help identify gene modules that facilitate the understanding of biological processes such as cell communication. Correlation measurement is the core basis for constructing a gene regulatory network. However, due to the high noise and sparsity in ST data, common correlation measurement methods such as the Pearson correlation coefficient (PCC) and Spearman correlation coefficient (SPCC) are not suitable. In this work, a new gene correlation measurement method called STgcor is proposed. STgcor defines vertexes as spots in a two-dimensional coordinate plane consisting of axes X and Y from the gene pair (X and Y). The joint probability density of Gaussian distribution of the gene pair (X and Y) is calculated to identify and eliminate outliers. To overcome sparsity, the degree, trend, and location of the distribution of vertexes are used to measure the correlation between gene pairs (X, Y). To validate the performance of the STgcor method, it is compared with the PCC and SPCC in a weighted coexpression network analysis method using two ST datasets of breast cancer and prostate cancer. The gene modules identified by these methods are then compared and analyzed. The results show that the STgcor method detects some special gene modules and cancer-related pathways that cannot be detected by the other two methods.

A review of the botany, ethnopharmacology, phytochemistry, analysis method and quality control, processing methods, pharmacological effects, pharmacokinetics and toxicity of codonopsis radix.

Codonopsis Radix, a traditional Chinese medicine in China, has great medicinal and scientific value. Moreover, it can also be used as a health product in daily diet. This paper reviews the botany, ethnopharmacology, phytochemistry, analysis method and quality control, processing methods, pharmacological effects, pharmacokinetics and toxicity related to Codonopsis Radix. The information of Codonopsis Radix is obtained from scientific databases (such as Baidu Scholar, CNKI, Google Scholar, PubMed, Science Direct, Web of Science, and SciFinder Scholar), Chinese herbal classics, Chinese Pharmacopoeia, PhD and MSc dissertations, and so on. The chemical components mainly include alkaloids, alkynes and polyacetylenes, flavonoids, lignans, steroids, terpenoids, organic acids, volatile oils, saccharides and other components, which have a wide range of neuroprotective effects, protection of gastrointestinal mucosa and anti-ulcer, regulation of body immunity, anti-tumor, endocrine regulation, improvement of hematopoietic function, cardiovascular protection, anti-aging and antioxidant effects. In conclusion, this paper summarizes in depth the shortcomings of the current research on Codonopsis Radix and proposes corresponding solutions. At the same time, this paper provides theoretical support for further research on the biological function and potential clinical efficacy of Codonopsis Radix.

Improving drug response prediction based on two-space graph convolution.

Patients with the same cancer types may present different genomic features and therefore have different drug sensitivities. Accordingly, correctly predicting patients' responses to the drugs can guide treatment decisions and improve the outcome of cancer patients. Existing computational methods leverage the graph convolution network model to aggregate features of different types of nodes in the heterogeneous network. They most fail to consider the similarity between homogeneous nodes. To this end, we propose an algorithm based on two-space graph convolutional neural networks, TSGCNN, to predict the response of anticancer drugs. TSGCNN first constructs the cell line feature space and the drug feature space and separately performs the graph convolution operation on the feature spaces to diffuse similarity information among homogeneous nodes. After that, we generate a heterogeneous network based on the known cell line and drug relationship and perform graph convolution operations on the heterogeneous network to collect the features of different types of nodes. Subsequently, the algorithm produces the final feature representations for cell lines and drugs by adding their self features, the feature space representations, and the heterogeneous space representations. Finally, we leverage the linear correlation coefficient decoder to reconstruct the cell line-drug correlation matrix for drug response prediction based on the final representations. We tested our model on the Cancer Drug Sensitivity Data (GDSC) and Cancer Cell Line Encyclopedia (CCLE) databases. The results indicate that TSGCNN shows excellent performance drug response prediction compared with other eight state-of-the-art methods.

Natural flavonoids alleviate glioblastoma multiforme by regulating long non-coding RNA.

Glioblastoma multiforme (GBM) is one of the most common primary malignant brain tumors in adults. Due to the poor prognosis of patients, the median survival time of GBM is often less than 1 year. Therefore, it is very necessary to find novel treatment options with a good prognosis for the treatment or prevention of GBM. In recent years, flavonoids are frequently used to treat cancer. It is a new attractive molecule that may achieve this promising treatment option. Flavonoids have been proved to have many biological functions, such as antioxidation, prevention of angiogenesis, anti-inflammation, inhibition of cancer cell proliferation, and protection of nerve cells. It has also shown the ability to regulate long non-coding RNA (LncRNA). Studies have confirmed that flavonoids can regulate epigenetic modification, transcription, and change microRNA (miRNA) expression of GBM through lncRNA at the gene level. It also found that flavonoids can induce apoptosis and autophagy of GBM cells by regulating lncRNA. Moreover, it can improve the metabolic abnormalities of GBM, interfere with the tumor microenvironment and related signaling pathways, and inhibit the angiogenesis of GBM cells. Eventually, flavonoids can block the tumor initiation, growth, proliferation, differentiation, invasion, and metastasis. In this review, we highlight the role of lncRNA in GBM cancer progression and the influence of flavonoids on lncRNA regulation. And emphasize their expected role in the prevention and treatment of GBM.

STING mediates SU5416/hypoxia-induced pulmonary arterial hypertension in rats by regulating macrophage NLRP3 inflammasome activation.

BACKGROUND: The NLRP3 inflammasome in macrophages is known to promote infection-related vascular growth, and NLRP3 inflammasome activation interacts with PAH. STING is a crucial inflammatory reaction link that can increase the overexpression of NLRP3. However, the expression and effect of STING in PAH have not been elucidated. We examined the expression and articulation of STING in PAH and researched its hidden mechanism. METHODS: A SU5416 plus hypoxia (Su/Hy)-induced rat model of PAH was constructed to examine STING activation. Su/Hy induced PAH rats were given a prophylactic injection of STING the inhibitor C-176. After modeling, hemodynamic changes, right ventricular hypertrophy index, lung morphological features, inflammasome activation, and proinflammatory cytokine secretion levels were assessed. In addition, the STING agonist DMXAA or inhibitor C-176 was used to interfere with LPS-induced BMDMs, NLRP3 inflammasome activation and cytokine secretion were examined, and the effect on PASMCs was evaluated in a coculture system. RESULTS: STING expression increased significantly in the lung tissue of Su/Hy-treated PAH rats compared with normoxia-treated rats. Moreover, STING inhibitors can alleviate the Su/Hy-induced increase in pulmonary artery pressure and restrain the activation of the NLRP3 inflammasome and proinflammatory cytokines. In vitro experiments confirmed that STING affected the expression of the NLRP3 inflammasome and the secretion of inflammatory cytokines in BMDMs and promoted the proliferation of PASMCs in the coculture system. CONCLUSION: Our study shows that STING is activated in Su/Hy-induced PAH and boosts the actuation of the macrophage NLRP3 inflammasome to advance the inflammatory response and vascular proliferation in rats with Su/Hy-induced pulmonary hypertension.

Echocardiographic evaluation of left atrial strain for predicting iron overload in pediatric patients with ß-thalassemia with preserved ejection fraction.

Pediatric patients with ß-thalassemia (ß-TM) with preserved ejection fraction may experience early myocardial damage. This prospective study aimed to investigate left atrial (LA) function restructure in pediatric patients with ß-TM by two-dimensional speckle tracking echocardiography (2D-STE) and evaluate the value of LA strain for predicting myocardial iron overload (MIO). We recruited 50 ß-TM pediatric patients and 30 healthy children aged 3-14 years. The patients were assigned to a normal left ventricular (LV) lesion group (n = 20) and an enlarged LV lesion group (n = 30). Subjects all underwent echocardiography to measure conventional cardiac function parameters and LA strain parameters. The results displayed that LA reservoir strain (LASr), conduit strain (LAScd), contractile strain (LASct) and strain rate were significantly reduced in pediatric patients with ß-TM with preserved ejection fraction. LASr, LAScd, and LASct were negatively correlated with the E/e' ratio, of which LASr had the most significant correlation (r = - 0.69, P < 0.001). LASr and LASct correlated positively with T2* (r = 0.70 and 0.62, respectively, all P < 0.001). In the multiple regression, LASr and LASct were independent predictors for T2*. The areas under the curve for LASr and LASct were 0.87 (P < 0.001) and 0.78 (P = 0.004), respectively. Our results demonstrated that LA strains were dramatically impaired in pediatric patients with ß-TM, and LASr is an efficient indicator for detecting LV early diastolic dysfunction in ß-TM pediatric patients and reflects early myocardial damage. LASr and LASct were independently predictive of MIO, but LASr was a more sensitive predictor.

Benchmarking of computational methods for predicting circRNA-disease associations.

Accumulating evidences demonstrate that circular RNA (circRNA) plays an important role in human diseases. Identification of circRNA-disease associations can help for the diagnosis of human diseases, while the traditional method based on biological experiments is time-consuming. In order to address the limitation, a series of computational methods have been proposed in recent years. However, few works have summarized these methods or compared the performance of them. In this paper, we divided the existing methods into three categories: information propagation, traditional machine learning and deep learning. Then, the baseline methods in each category are introduced in detail. Further, 5 different datasets are collected, and 14 representative methods of each category are selected and compared in the 5-fold, 10-fold cross-validation and the de novo experiment. In order to further evaluate the effectiveness of these methods, six common cancers are selected to compare the number of correctly identified circRNA-disease associations in the top-10, top-20, top-50, top-100 and top-200. In addition, according to the results, the observation about the robustness and the character of these methods are concluded. Finally, the future directions and challenges are discussed.

The reliability and integrity of overall survival data based on follow-up records only and potential solutions to the challenges.

Overall survival (OS) is considered the standard clinical endpoint to support effectiveness claims in new drug applications globally, particularly for lethal conditions such as cancer. However, the source and reliability of OS in the setting of clinical trials have seldom been doubted and discussed. This study first raised the common issue that data integrity and reliability are doubtful when we collect OS information or other time-to-event endpoints based solely on simple follow-up records by investigators without supporting material, especially since the 2019 COVID-19 pandemic. Then, two rounds of discussions with 30 Chinese experts were held and 12 potential source scenarios of three methods for obtaining the time of death of participants, including death certificate, death record and follow-up record, were sorted out and analysed. With a comprehensive assessment of the 12 scenarios by legitimacy, data reliability, data acquisition efficiency, difficulty of data acquisition, and coverage of participants, both short-term and long-term recommended sources, overall strategies and detailed measures for improving the integrity and reliability of death date are presented. In the short term, we suggest integrated sources such as public security systems made available to drug inspection centres appropriately as soon as possible to strengthen supervision. Death certificates provided by participants' family members and detailed standard follow-up records are recommended to investigators as the two channels of mutual compensation, and the acquisition of supporting materials is encouraged as long as it is not prohibited legally. Moreover, we expect that the sharing of electronic medical records and the legal disclosure of death records in established health registries can be realized with the joint efforts of the whole industry in the long-term. The above proposed solutions are mainly based on the context of China and can also provide reference for other countries in the world.