BACKGROUND: In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration. METHODS: A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases. RESULTS: MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05). CONCLUSIONS The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.
Humans ; Lung Neoplasms/genetics* ; Adenocarcinoma of Lung/genetics* ; China ; Prognosis ; Transcription Factors

In recent years,with the rapid development and widespread popularity of smartphones,analytical sensors based on different action principles have provided an effective solution for forensic real-time detection.In this paper,the recent progress of smartphone-based systems of analytical sensors in forensic real-time detection was reviewed.The analytical principle,the performance of different analytical sensing,and their future perspectives were discussed respectively.

In the past few decades, the global obesity population has been increasing, and still has an upward trend. With obesity, the risk of cardiovascular and cerebrovascular diseases has increased. It’s found that an increase in body mass index is associated with the occurrence of some cardiovascular and cerebrovascular diseases Hypertension and hyperlipidemia, as common chronic cardiovascular diseases, are particularly affected by obesity, which has attracted extensive attention in recent years. Moreover, the occurrence of hypertension and hyperlipidemia under the influence of obesity is significantly related, and their synergy can also cause a variety of cardiovascular and cerebrovascular diseases. However, there is still less work to study these three factors at the same time. Therefore, on the basis of summarizing the molecular mechanisms of obesity affecting hypertension and hyperlipidemia, this paper summarizes the relevant molecular mechanisms of hypertension and hyperlipidemia under the influence of obesity, and points out the co-acting molecules, providing a reference for future research on cardiovascular and cerebrovascular diseases.

Objective To evaluate the clinical efficacy of comprehensive treatment for synchronous primary advanced gastric and esophageal cancer by propensity score matching(PSM).Methods A total of 2 551 patients with advanced gastric cancer admitted to Jiangsu Province Hospital of Chinese Medicine from January 2013 to December 2022 were retrospectively analyzed.Among them,45 patients with synchronous primary esophageal cancer were distributed to the observation group,and 2 506 patients without esophageal cancer were distributed to the control group.Through the PSM method,the control group was matched with the observation group and the equilibrium samples of covariates between two groups were obtained.The overall survival(OS)between the two groups were compared.Results Both observation and control group contained 45 patients in this study.According to the treatment regimen,the patients in the observation group was divided into radical resection treatment subgroup(n=22)and chemoradiotherapy(CRT)subgroup(n=23).In the radical resection subgroup,4 patients underwent the simultaneous surgical resection of gastric and esophageal tumors through proximal gastrectomy with the Ivor Lewis operation.Eighteen patients underwent endoscopic submucosal dissection(ESD)of their esophageal tumors and gastric cancer radical resection.Radical resection of gastric cancer combined with preoperative chemoradiotherapy of esophageal cancer was performed in the CRT subgroup.Survival analysis showed that OS in the observation group was significantly shorter than that in the control group(P=0.042)and there was no significant difference in OS between the radical resection subgroup and the control group(P=0.799).The 1-,3-,and 5-year survival rates of the patients in the CRT subgroup were significantly lower than those of the control group(P=0.003).While the 1-,3-,and 5-year survival rates of the patients in the radical resection subgroup were not statistically significant,compared to those of the CRT subgroup(P=0.071).Conclusions Multidisciplinary and comprehensive treatment can significantly improve the prognosis of patients with synchronous primary advanced gastric and esophageal cancer.Radical resection of gastric cancer combined with ESD of esophageal cancer is an optional treatment for patients with gastric cancer complicated with early esophageal cancer.Radical resection of gastric cancer combined with CRT of esophageal cancer can improve the prognosis of patients with advanced gastric cancer complicated with unresectable esophageal cancer.

Objective To summarize current status of multidrug-resistant organism (MDRO) infection in lung transplant recipients and analyze the risk factors of MDRO infection. Methods Clinical data of 321 lung transplant recipients were retrospectively analyzed. According to the incidence of postoperative MDRO infection, they were divided into the MDRO group (n=122) and non-MDRO infection group (n=199). The incidence of MDRO infection in lung transplant recipients was summarized. The risk factors of MDRO infection in lung transplant recipients were analyzed by logistic regression model. The dose-response relationship between MDRO infection and time of ventilator use was determined by restricted cubic spline model. Results Among 321 lung transplant recipients, 122 cases developed MDRO infection, with an infection rate of 38.0%. Two hundred and twenty-nine strains of pathogenic bacteria were detected in the MDRO infection group, mainly Gram-negative bacteria (92.6%), and the top three strains were carbapenem-resistant acinetobacter baumannii (46.3%), carbapenem-resistant pseudomonas aeruginosa (22.3%) and carbapenem-resistant klebsiella pneumoniae (14.8%), respectively. MDRO infection mainly consisted of lower respiratory tract infection (61.5%), followed by ventilator-associated pneumonia (26.2%). Univariate analysis showed that the risk factors of MDRO infection in lung transplant recipients were single-lung transplantation, long-time postoperative use of extracorporeal membrane oxygenation (ECMO), long operation time, long-time urinary catheterization, long-time central venous catheterization and long-time ventilator use (all P < 0.05). Multivariate logistic regression analysis indicated that single-lung transplantation and long-time ventilator use were the independent risk factors for MDRO infection in lung transplant recipients (both P < 0.05). Results of restricted cubic spline model analysis showed that the risk of infection continued to increase with the prolongation of ventilator use time within 20 d. After 20 d, prolonging the time of ventilator use failed to increase the risk of infection, showing a plateau effect. Conclusions The MDRO infection rate tends to decline in lung transplant recipients year by year. Single-lung transplantation and long-time ventilator use are the independent risk factors for MDRO infection in lung transplant recipients.

Aromatic compounds make up a large part of fragrances and are traditionally produced by chemical synthesis and direct extraction from plants. Chemical synthesis depends on petroleum resources and has disadvantages such as causing environment pollutions and harsh reaction conditions. Due to the low content of aromatic compounds in plants and the low yield of direct extraction, plant extractions require large amounts of plant resources that occupy arable land. In recent years, with the development of metabolic engineering and synthetic biology, microbial synthesis of aromatic compounds from renewable resources has become a promising alternative approach to traditional methods. This review describes the research progress on the synthesis of aromatic fragrances by model microorganisms such as Escherichia coli or yeast, including the synthesis of vanillin through shikimic acid pathway and the synthesis of raspberry ketone through polyketide pathway. Moreover, this review highlights the elucidation of native biosynthesis pathways, the construction of synthetic pathways and metabolic regulation for the production of aromatic fragrances by microbial fermentation.
Biosynthetic Pathways ; Metabolic Engineering ; Odorants ; Shikimic Acid ; Synthetic Biology

Cases of 2019-nCoV nucleic acid and antibody (IgM and IgG total antibody) after discharge from a hospital in Chongqing were continuously monitored. It was found that 5 cases of "re-positive" phenomenon, 5 cases of antibody were positive, and there was a trend of increasing with time. "Re-Positive" may be related to the following three factors. Children with asymptomatic infection had a long time of fecal detoxification.There were two consecutive nucleic acid tests "false negative" caused by various reasons.The virus clearance in patients was not complete, and the discharge standard was not conservative enough. The analysis of the causes of "Re-Positive" patients and the discussion of its infection will help us reveal more characteristics of this virus, and to provide a new basis for the discharge standard in the constantly updated diagnosis and treatment programme.

Objective To compare the therapeutic effects between three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT) in patients with stage Ⅱ/Ⅲ esophageal cancer and investigate the prognostic factors.Methods Medical record of 2 132 patients with stage Ⅱ/Ⅲ esophageal cancer who underwent definitive radiotherapy with/without chemotherapy in 10 hospitals from January 2002 to December 2016 from were retrospectively analyzed.Among these patients,37.9％ of them were aged ≥ 70 years,33.9％ with neck and upper esophageal tumors and 66.1％ with middle and lower esophageal and borderline tumors.The median gross tumor volume (GTV) and lymph node gross tumor volume (GTVnd) was 41.6 cm3.Among them,32％ were stage Ⅱ] and 68％ were stage Ⅲ.A total of 723 patients received 3DCRT and 1 409 cases received IMRT.Patients received an equivalent dose in 2 Gy (EQD2) ≥ 60 Gy accounted for 86.1％,and 41.1％ of them received concurrent chemoradiotherapy.Results The median follow-up time was 60.8 months.The 1-,3-and 5-year overall survival (OS) of all patients was 73.9％,41.7％ and 32.6％,and the 1-,3-and 5-year progression-free survival (PFS) was 62.2％,37.3％ and 32％,respectively.Multivariate analysis demonstrated that age,primary tumor location,clinical stage,tumor target volume,EQD2 and concurrent chemoradiotherapy were the independent prognostic factors for OS.Age,primary tumor location,clinical stage,tumor target volume and EQD2 were the independent prognostic factors for PFS.The OS and PFS did not significantly differ among the low-risk,low-/moderate-risk,moderate-/high-risk and high-risk groups according to age≥70 years,tumor diameter＞5 cm,tumor volume ≥41.6 cm3 and stage Ⅲ (P＜0.001).After the propensity score matching (PSM) method,neither 3DCRT nor IMRT yielded significant advantages in OS or PFS (P=0.971;P=0.658).However,IMRT tended to yield survival benefits in low-risk patients (P=0.125).Conclusions Both 3DCRT and IMRT yield relatively high OS rate in patients with stage Ⅱ/Ⅲ esophageal cancer.The prognosis model established in this investigation can properly predict the survival of patients.Low-risk patients tend to obtain survival benefits from IMRT.

Pichia pastoris is one of the most convenient and widely used heterologous protein expression systems. To further improve its ability to express heterologous proteins, we developed a high-throughput P. pastoris screening method based on droplet microfluidic and demonstrated the method by screening and obtaining mutants with enhanced xylanase expression and secretion abilities. We used PCR (Polymerase Chain Reaction) amplification to obtain a fusion fragment of xylanase xyn5 gene and green fluorescent protein gfp gene, and cloned this fragment into pPIC9K, the expression vector of Pichia pastoris, to construct the plasmid pPIC9K-xyn5-gfp that recombined the DNA fragments of xylanase and green fluorescent protein. After this plasmid entered P. pastoris GS115 by electroporation, the P. pastoris SG strain that could express xylanase and green fluorescent protein was obtained. The above-said strains were then mutagenized by atmospheric room temperature plasma and subsequently encapsulated to form single-cell droplets. After 24-hour cultivation of the droplets, microfluidic screening was carried out to obtain the mutant strain with high xylanase expression for further construction and screening of the next mutagenesis library. After five rounds of droplet microfluidic screening, a highly productive strain P. pastoris SG-m5 was obtained. The activity of the expressed xylanase was 149.17 U/mg, 300% higher than that of those expressed by the original strain SG. This strain's ability to secrete heterologous protein was 160% higher than that of the original strain. With a screening throughput of 100 000 strains per hour, the high-throughput P. pastoris screening system based on single-cell droplet microfluidic developed by the present study screens a library with million strains in only 10 hours and consumes only 100 μL of fluorescent reagent, thus reducing the reagent cost by millions of times compared with the traditional microplate screening and more importantly, providing a novel method to obtain P. pastoris with high abilities to express and secret heterologous proteins by efficient and low-cost screening.
Microfluidics ; Mutagenesis ; Pichia ; Plasmids ; Polymerase Chain Reaction ; Recombinant Proteins

Objective To evaluate the clinical efficacy and adverse events of intensity-modulated radiotherapy ( IMRT ) in the treatment of intermediate risk localized prostate cancer, and analyze the significance of prostate-specific antigen ( PSA) level changes. Methods Clinical data of 66 patients with intermediate risk localized prostate cancer admitted to our hospital between 2007 and 2018 were retrospectively analyzed. Sixty patients were treated with endocrine therapy before radiotherapy. The radiation field covered the pelvic lymph node drainage area in 6 cases. Forty-seven patients received image-guided radiotherapy ( IGRT) . The median dose in the prostate and seminal vesicle was 78 Gy and 48 Gy in the pelvic lymph node drainage area. The survival rate was calculated using the Kaplan-Meier method. Results The median age was 77 years. The median follow-up time was 71. 3 months. The 5-year sample size was 47. The 3-and 5-year overall survival (OS) was 98％ and 90％.The 3-and 5-year cancer-specific survival (CSS) was 100％ and 93％.The 3-and 5-year biochemical relapse-free survival was 97％ and 86％. The mean time of PSA declining to the nadir was 5. 83 months. The median level of PSA nadir was 0. 06 ng/ml after IMRT. The incidence of grade I andⅡearly adverse events in the urinary system was 38％ and 6％. The incidence of grade I andⅡearly adverse events in the gastrointestinal system was 21％ and 3％. The incidence of grade I andⅡadvanced-stage adverse events in the urinary system was 9％ and 2％. The incidence of grade I advanced-stage adverse events in the gastrointestinal system was 5％. Conclusions IMRT yields high clinical efficacy in the treatment of intermediate risk localized prostate cancer with a low risk of adverse events in the early and advanced stage. The monitoring of PSA after IMRT contributes to the assessment of clinical prognosis.