SCSsim: an integrated tool for simulating single-cell genome sequencing data.

MOTIVATION: Allele dropout (ADO) and unbalanced amplification of alleles are main technical issues of single-cell sequencing (SCS), and effectively emulating these issues is necessary for reliably benchmarking SCS-based bioinformatics tools. Unfortunately, currently available sequencing simulators are free of whole-genome amplification involved in SCS technique and therefore not suited for generating SCS datasets. We develop a new software package (SCSsim) that can efficiently simulate SCS datasets in a parallel fashion with minimal user intervention. SCSsim first constructs the genome sequence of single cell by mimicking a complement of genomic variations under user-controlled manner, and then amplifies the genome according to MALBAC technique and finally yields sequencing reads from the amplified products based on inferred sequencing profiles. Comprehensive evaluation in simulating different ADO rates, variation detection efficiency and genome coverage demonstrates that SCSsim is a very useful tool in mimicking single-cell sequencing data with high efficiency. AVAILABILITY AND IMPLEMENTATION: SCSsim is freely available at https://github.com/qasimyu/scssim. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Major Adverse Cardiovascular Events Among Obese Patients with Diabetes After Metabolic and Bariatric Surgery: a Meta-analysis of Matched Cohort and Prospective Controlled Studies with 122,361 Participates.

PURPOSE: Metabolic and bariatric surgery (MBS) can exert effective function on glycemic control. The present study aimed to estimate the risk of MACE among obese patients with diabetes after MBS. MATERIALS AND METHODS: Systematic search of PubMed, Embase, Medline, and Web of Science was performed for studies published before 20th February 2023. The odds ratio (OR) corresponding to the 95% confidence interval (95% CI) was used to assess the outcome. The statistical heterogeneity among studies was assessed with the Q-test and I2 statistics. RESULTS: Fifteen cohort studies with 122,361 obese patients with diabetes were available for analysis. Our meta-analysis found significantly decreased morbidity and mortality of MACE (OR = 0.65, 95% CI = 0.59-0.72, I2 = 62.8% for morbidity, OR = 0.49, 95% CI = 0.36-0.67, I2 = 68.7% for mortality). Subgroup analysis revealed MBS decreased cerebrovascular disease, coronary artery disease, atrial fibrillation, heart failure, myocardial infarction, and stroke risk. CONCLUSION: Our meta-analysis indicated that MBS for obese patients with diabetes is beneficial to decreasing MACE risk. Moreover, further studies estimating the functional effect may eventually provide a better and comprehensive understanding of the effect on different populations.

The effect of metformin on mortality and severity in COVID-19 patients with diabetes mellitus.

AIM: COVID-19 has spread globally with heavy impact on most countries and our therapeutic strategies in COVID-19 patients with diabetes are still limited. Recently, some new information was added to this field. We performed this updated meta-analysis to reveal the underlying effect of metformin on COVID-19 patients with diabetes. METHODS: We searched the PubMed, Embase and CNKI (China National Knowledge Infrastructure) databases for all articles. The odds ratio (OR) corresponding to the 95% confidence interval (95% CI) was used to assess the effect of metformin on COVID-19 patients with diabetes. The statistical heterogeneity among studies was assessed with the Q-test and I2 statistics. RESULTS: We collected 17 studies including 20,719 COVID-19 patients with diabetes. Our results found that metformin was associated with significantly decreased mortality and severity in COVID-19 patients with diabetes (OR = 0.64, 95% CI = 0.51-0.79 for mortality, and OR = 0.81, 95% CI = 0.66-0.99 for severity). CONCLUSIONS: Our meta-analysis indicated that following metformin treatment might benefit the patients with T2DM, both the mortality and severity. However, patients with severe COVID-19 should be monitored closely for the development of lactic acidosis, acidosis, and decreased kidney function.

Screening of the HBx transactivation domain interacting proteins and the function of interactor Pin1 in HBV replication.

Hepatitis B virus (HBV) X protein (HBx) has been determined to play a crucial role in the replication and transcription of HBV, and its biological functions mainly depend on the interaction with other host proteins. This study aims at screening the proteins that bind to the key functional domain of HBx by integrated proteomics. Proteins that specifically bind to the transactivation domain of HBx were selected by comparing interactors of full-length HBx and HBx-D5 truncation determined by glutathione-S-transferase (GST) pull-down assay combined with mass spectrometry (MS). The function of HBx interactor Pin1 in HBV replication was further investigated by in vitro experiments. In this study, a total of 189 proteins were identified from HepG2 cells that specifically bind to the transactivation domain of HBx by GST pull-down and subsequent MS. After gene ontology (GO) analysis, Pin1 was selected as the protein with the highest score in the largest cluster functioning in protein binding, and also classified into the cluster of proteins with the function of structural molecule activity, which is of great potential to be involved in HBV life cycle. The interaction between Pin1 and HBx has been further confirmed by Ni2+-NTA pulldown assay, co-immunoprecipitation, and immunofluorescence microscopy. HBsAg and HBeAg levels significantly decreased in Pin1 expression inhibited HepG2.2.15 cells. Besides, the inhibition of Pin1 expression in HepG2 cells impeded the restored replication of HBx-deficient HBV repaired by ectopic HBx expression. In conclusion, our study identified Pin1 as an interactor binds to the transactivation domain of HBx, and suggested the potential association between Pin1 and the function of HBx in HBV replication.

Emergency surgical workflow and experience of suspected cases of COVID-19: A case report.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 has been confirmed to be a newly discovered zoonotic pathogen that causes highly contagious viral pneumonia, which the World Health Organization has named novel coronavirus pneumonia. Since its outbreak, it has become a global pandemic. During the outbreak of coronavirus disease 2019 (COVID-19), however, there is no mature experience or guidance on how to carry out emergency surgery for suspected cases requiring emergency surgical intervention and perioperative safety protection against virus. CASE SUMMARY: A 41-year-old man was admitted to the hospital for emergency treatment due to "3-d abdominal pain aggravated with cessation of exhaust and defecation". After improving inspections and laboratory tests, the patient was assessed and diagnosed by the multiple discipline team as "strangulation obstruction, pulmonary infection". His body temperature was 38.8 °C, and the chest computed tomography showed pulmonary infection. Given fever and pneumonia, we could not rule out COVID-19 after consultation by fever clinicians and respiratory experts. Hence, we performed emergency surgery under three-level protection for the suspected case. After surgery, his nucleic acid test for COVID-19 was negative, meaning COVID-19 was excluded, and routine postoperative treatment and nursing was followed. The patient was treated with symptomatic support after the operation. The stomach tube and urinary tube were removed on the 1st d after the operation. The clearing diet was started on the 3rd d after the operation, and the body temperature returned to normal. Flatus and bowel movements were noted on 5th postoperative day. He was discharged after 8 d of hospitalization. The patient was followed up for 4 mo after discharge, no serious complications occurred. A 71-year-old woman was admitted to our emergency room due to "abdominal distention, fatigue for 6 d and fever for 13 h". After the multiple discipline team evaluation, the patient was diagnosed as "intestinal obstruction, abdominal mass, peritonitis and pulmonary infection". At that time, the patient's body temperature was 39.6 °C, and chest computed tomography indicated pulmonary infection. COVID-19 could not be completely excluded after consultation in the fever outpatient department and respiratory department. Therefore, the patient was treated as a suspected case, and an urgent operation was performed under three-level medical protection. Postoperative nucleic acid test was negative, COVID-19 was excluded, and routine postoperative treatment and nursing were followed. After the operation, the patient received symptomatic and supportive treatment. The gastric tube was removed on the 1st d after the operation, and the urinary tube was removed on the 3rd d after the operation. Enteral nutrition began on the 3rd d after the operation. To date, no serious complications have been found during follow-up after discharge. CONCLUSION: Based on the previous treatment experience, we reviewed the procedures of two cases of suspected COVID-19 emergency surgery and extracted the perioperative protection experience. By referring to the literature and following the regulations on prevention and management of infectious diseases, we have developed a relatively mature and complete emergency surgical workflow for suspected COVID-19 cases and shared perioperative protection and management experience and measures.

microRNA-582 Potentiates Liver and Lung Metastasis of Gastric Carcinoma Cells Through the FOXO3-Mediated PI3K/Akt/Snail Pathway.

BACKGROUND: The dysregulation of microRNA (miRNAs) is broadly participated in cancer progression, resulting in sustained cell proliferation by directly targeting various targets. This study investigated the expression of miR-582 in GC and its association with liver metastasis. METHODS: Firstly, differentially expressed miRNAs in gastric cancer (GC) tissues were predicted by microarray. Then, the relationship between miR-582 and clinical characteristics of GC patients was analyzed. By silencing of miR-582 in GC cells, the change in malignant biological behaviors of GC cells was detected. The upstream lncRNA, downstream targeting genes of miR-582 and the corresponding signaling pathway were predicted by online databases and verified by luciferase reporter assays, RT-qPCR and Western blot analysis. Finally, the effects of miR-582 on the growth and metastasis of GC cells were detected by in vivo tumorigenesis and metastasis tests. RESULTS: MiR-582 was highly expressed in GC tissues and related to the metastasis of patients with GC. Silencing of miR-582 expression blocked malignant biological behaviors of GC cells in vitro and in vivo. MiR-582 inhibited forkhead box protein O3 (FOXO3) to upregulate the PI3K/AKT/Snail signaling pathway in GC cells. Besides, GATA6-AS1 was found as an upstream lncRNA to modulate the expression of miR-582. CONCLUSION: MiR-582 induced by GATA6-AS1 silencing promotes the growth and metastasis of GC cells by targeting FOXO3 to induce the activation of the PI3K/AKT/Snail signaling pathway. MiR-582 could be a potential molecular therapy target for patients with GC.