Background: Male urethral stricture is a disease with a high incidence rate. With social-economic development in the developing countries, the trend of etiology and treatment of male urethral stricture changed was speculated.Methods: The clinical data of the male patients with urethral stricture from 2000 to 2019 were analyzed. The subjects were divided into Group A (2000–2009) and Group B (2010–2019) according to treatment time. The pooled analysis of the data extracted from pieces of literature was also performed.Results: About 540 patients were included in the present study, including 235 patients in Group A and 305 patients in Group B. In recent 10 years, trauma has still been the main cause of urethral stricture. Iatrogenic injury, especially transurethral operation, increases significantly, while male urethral stricture secondary to radiotherapy and infection decrease. Urethroplasty increases and the reoperation rate decreases in treating simple urethral stricture, and flap urethroplasty also increases in treating complex urethral stricture. The results of a pooled analysis of data from 11 centers in Mainland China are partially consistent with it. Complications, such as urethral fistula, false canal, ejaculation disorder, and penile curvature, decrease significantly.Conclusions: The main causes of urethral stricture in the recent 10 years are still trauma and iatrogenic injuries, and the etiology of urethral stricture is related to socioeconomic development. With the increase of intracavitary minimally invasive treatment and flap urethroplasty, the curative effect is increasing, while iatrogenic urethral stricture cannot be ignored. Male urethral stricture (MUS) is a common disease and manifested by dysuria, which is often accompanied by urinary tract infection, and even damages renal function, causes male sexual dysfunction, and lowers the quality of life of patients . Due to The Center attracts many patients with MUS from the whole province and surrounding areas. The clinical data of patients with MUS were collected in the present study, and the trends of etiology, treatment methods, and outcomes of them were analyzed in the past 20 years, aiming to fill pieces of literature in this field.Patients with MUS treated in The Second Xiangya Hospital of Central South University from January 2000 to December 2019 were included. The present study was approved by the Ethics Committee of the Hospital, and informed consent was obtained from each patient. The authors had no access to information that could identify individual participants during or after data collection. Inclusion criteria were as follows: (1) ≥18 years old; (2) patients with a history of MUS; (3) patients with symptomatic MUS diagnosed by urethroscopy and urethrography; (4) patients who received treatment related to MUS, but failed to recover; (5) patients with external urethral orifice stricture, and diagnosed with lichen sclerosus. Exclusion criteria were as follows: (1) patients with MUS caused by malignant tumors; (2) patients with untreated hypospadias; (3) patients diagnosed with MUS, accompanied by acute urinary tract infection for the first time, and only received suprapubic cystostomy and anti-infective therapy.Strengthening the Reporting of Observational Studies in Epidemiology Guidelines for Cohort Studies.The present study was a single-center, retrospective, and observational study. The included patients were assigned into two groups according to the primary visitation date: Group A (January 2000–December 2009) and Group B (January 2010–December 2019). This study was reported according to the The clinical data of basic characteristics, stricture site, etiology, comorbidities and treatment strategies, and one-year follow-up were collected.Criteria for effective treatment: within 1 year after the urethral catheter was removed; the diameter of the urethra was ≥10 F under cystoscopy. The patients were satisfied with excretion of urination and experienced no obvious dysuria or dripping. Furthermore, the International Prostate Symptoms Score (IPSS) was ≤ 12, the Quality of Life (QoL) score was ≤ 3, and the urodynamic test Qmax was ≥15 ml/s. No distinction was made on whether self-catheterization or urethral dilatation was performed in the analysis. Definition of a complex MUS is given as follows: (1) posterior MUS of >2 cm, surrounded by scars caused by pelvic floor hematoma muscularization; (2) accompanied by diverticulum, false tract, and fistulous tract, regardless of the length of the MUS; (3) accompanied by urethral sphincter injury .The clinical data were collected by two researchers independently and submitted to a third researcher for verification. Conflicts in the data were further verified by a third researcher. In addition, the number of patients with missing follow-up data was controlled strictly. When the number of patients lost to follow-up exceeded 10% of the total 560 patients, the general characteristics of the patients who were lost to follow-up and those who were not lost to follow-up were compared.In order to make the sample more representative and make further comparisons from different aspects, multicenter data were included in the study. China was a developing country with uneven economic and social development. The pooled analysis was based on two consensuses: (1) the social economy is developing over time no matter in which region of China; (2) in the same time, the social economic level gradually increased from the northwest to the southeast in China, and this trend has not changed in the past 20 years. We controlled one of the variables in each step of pooled analysis. A literature retrieval was performed in March 2021 using the China National Knowledge Infrastructure databases. Studies on MUS conducted in different periods and in areas with different economic development levels were selected, and then clinical data were partially extracted and added to our data for pooled analysis. The analysis process included two parts: first, the patients were grouped by treatment time, and then the comparison of the MUS site, etiology, and treatment options was conducted so as to reveal the trend of the disease in China over time; second, the patients were divided into two groups according to the economic level of the area where the hospital is located, and then the same comparison was performed so as to reveal the trend of the disease with different economic levels in Mainland China.p < 0.05 was defined as statistically significant. If the data followed a normal distribution and showed equal variance, Student's T-test was performed; when the data did not show a normal distribution or homoscedasticity, the Mann–Whitney U test was performed. The mean and SD are expressed as x ±s. Qualitative data were analyzed using Pearson's χ2 test (N ≥ 40 and T ≥ 5), the continuity correction χ2 test (N ≥ 40 and 1 ≤ T < 5), or Fisher's exact test (n < 40 or <1).All data were processed with SPSS 22.0 Software, and a two-sided A total of 540 patients were included in the present study. There were 235 patients in Group A (January 2000–December 2009), and the average age of them was 52.79 ± 14.40 years old. There were 305 patients in Group B (January 2010–December 2019), and the average age was 53.18 ± 15.35 years. There was no significant difference in the length and the site of the urethral stricture between these two groups. The follow-up data were missing in 16 patients in Group A and 17 patients in Group B. This was <10% of the sample size.P = 0.022), while the urethral stricture caused by pelvic radiotherapy and urinary tract infection significantly decreased   .P = 0.000), while the number of patients who received direct visual balloon dilatation significantly increased (P = 0.000)  .P = 0.000), while the patients who received direct visual internal urethrotomy decreased to 14.55% (P = 0.019)  in Group B increased to 87.88%, especially with flap urethroplasty (= 0.019) .P = 0.103), and the reoperation rate within 1 year decreased from 53.95 to 31.30% (P = 0.011). At the same time, the times of dilations and regular urethral dilatation periods in Group B significantly improved, when compared with Group A  (P = 0.181), and the reoperation rate within 1 year decreased from 27.27 to 14.01% (P = 0.004). The reoperation methods mainly included open surgery and direct visual internal urethrotomy.This part of the results is shown in = 0.000) . For theP = 0.043), and the proportion of urinary fistula or false tract in Group B decreased from 18.42 to 7.63% (P = 0.019). For the patients with complex urethral stricture, compared with Group A, the proportion of penile curvature after surgery in Group B decreased from 13.99 to 7.01% (P = 0.047), and the proportion of ejaculation disorder in Group B decreased from 11.89 to 5.10% (P = 0.033). However, there was no significant difference in the remaining complications between these two groups.Postoperative complications are listed in Clinical data of 11 centers in Mainland China extracted from five studies were included in the pooled analysis. A trend over time is shown in A trend over the economic level is shown in With the rapid social-economic development in China, the etiology and treatment for MUS have changed in recent years. The present retrospective study revealed that trauma has always been the main cause of MUS in Hunan Province, which is much higher than in developed countries and is similar to that in developing countries –8. TheseThe pooled analysis further showed the increase of MUS was caused by the transurethral procedure and the decrease of stricture was caused by urethra infection, because of the gradual promotion of transurethral minimally invasive surgery and improvement of sanitary conditions in Mainland China. In addition, the pooled analysis revealed that the MUS site was different with treatment time and regions, which might be related to the etiological changes of MUS. The pooled analysis of the two parts both reflected the trend of disease characteristics with the socioeconomic development from a larger scale, which thereby better strengthened some of the conclusions of the present study. However, the pooled analysis also showed some different or even competing results from this study. The positive reason may be the increase in statistical power by the large sample, and the negative reason may be the heterogeneity between studies, which led to bias.With the improvement of surgical technology and growing demands for quality of life and reduction in complications, more and more patients with complex MUS received flap urethroplasty in our hospital, which was consistent with the results of pooled analysis. Urethroplasty is of long-term effectiveness and is being increasingly performed in developed countries . In ChinThe common causes for hematuria were lack of electric energy and urethral mucosa injury during the urethral dilatation. In Group B, the less use of blind metal sound urethral dilatation might contribute to reducing bleeding complications. Open surgery often led to penile curvature, abnormal ejaculation, and urethral fistula –15; the However, there are some limitations to this study. First, the present study is a single-center investigation with a limited duration of follow-up. Second, the present study included the patients who failed to recover from multiple treatments in other hospitals, which might influence treatments. Third, the heterogeneity between studies might lead to bias in the pooled analysis.The present study still indicates the trends of MUS in Hunan, or even in Mainland China, which is socioeconomic development related. The main causes of urethral stricture in the past 10 years were still trauma and iatrogenic injuries. With the increase of intracavitary minimally invasive treatment and flap urethroplasty, the curative effect is increasing, while iatrogenic urethral stricture cannot be ignored.The raw data supporting the conclusions of this article will be made available by the authors without undue reservation.The studies involving human participants were reviewed and approved by the Ethics Committee of the Second Xiangya Hospital of Central South University. The patients/participants provided their written informed consent to participate in this study.YW and SP: conception and design. YW and SP: administrative support. XC, MD, LZ, YL, and SC: provision of study materials or patients. XC, MD, MP, LZ, YL, SP, and SC: collection and assembly of data. XC, MD, MP, and SP: data analysis and interpretation. XC and MD: manuscript writing. All authors: final approval of the manuscript.This work was supported by grants from the Hunan Province Innovation Platform and Talent Program-Clinical Medical Research Center (Grant No. 2019SK4003) and The Scientific Research Project of Hunan Health Commission (Grant Nos. C2019162 and B2019161).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Soil moisture content (SMC) plays an essential role in geoscience research. The SMC can be retrieved using an artificial neural network (ANN) based on remote sensing data. The quantity and quality of samples for ANN training and testing are two critical factors that affect the SMC retrieving results. This study focused on sample optimization in both quantity and quality. On the one hand, a sparse sample exploitation (SSE) method was developed to solve the problem of sample scarcity, resultant from cloud obstruction in optical images and the malfunction of in situ SMC-measuring instruments. With this method, data typically excluded in conventional approaches can be adequately employed. On the other hand, apart from the basic input parameters commonly discussed in previous studies, a couple of new parameters were optimized to improve the feature description. The Sentinel-1 SAR and Landsat-8 images were adopted to retrieve SMC in the study area in eastern Austria. By the SSE method, the number of available samples increased from 264 to 635 for ANN training and testing, and the retrieval accuracy could be markedly improved. Furthermore, the optimized parameters also improve the inversion effect, and the elevation was the most influential input parameter. The soil moisture content (SMC) refers to the volume of water present in the gaps between surface soil granules. The SMC is a critical parameter for investigating and predicting the factors associated with climate change. It also plays a key role in various fields of science such as ecology, hydrology, and agriculture ,2,3. HowRegarding microwave data, theoretical and semi-empirical models have been established for SMC estimation, such as the integral equation model (IEM) , advanceAs a non-linear empirical model, the artificial neural network (ANN) can build an implicit relationship between input data and output targets, and it has been proven effective for SMC retrieval . StudiesAs we know, samples are the key elements of ANN. To obtain ideal retrieval results, both the quantity and quality of the samples for ANN training and testing should be guaranteed. That is to say, not only should the sample pool be large enough, but also the input parameters of the samples should be inclusive of the features that are helpful to accurate SMC retrieval. As for the quantitative optimization, sufficient samples are conducive to improving the training accuracy and representing various geographical situations ,31,32. IFor one thing, the use of optical images is associated with contamination from clouds, thick fogs, and mists , which mTo address the problem of quantitative optimization, a novel sparse sample exploitation (SSE) method was proposed, whereby a part of the samples that were otherwise excluded could be sufficiently utilized and incorporated into the SMC retrieval procedure. To address the problem of qualitative optimization, we extended the array of input parameters of ANN for SMC retrieval. Apart from the radar incidence angle, VH/VV backscattering coefficients and NDVI, which were included in this paper as the basic input parameters, parameters such as LST, land cover type, elevation, slope, and data acquisition time, are likewise considered as the inputs of ANN in this paper. The sensitivity of SMC retrieval to these parameters was discussed.The rest of this paper is organized as follows. In The study area is located in the eastern part of Austria . Comparehttps://ismn.geo.tuwien.ac.at/, accessed on 20 January 2022) [Ground truth data come from The International Soil Moisture Network (ISMN), which was implemented in 2009 aiming exclusively to validate and calibrate SMC retrieval with RS techniques. The data are qualitatively controlled after collecting them from the networks and then distributed on the website portal (ry 2022) ,41. Thishttps://earthexplorer.usgs.gov/, accessed on 20 January 2022), were selected. The span period was from January 2016 to April 2020, and the spatial resolution of the images was 30 m. Based on the method described in The optical RS data employed in this study was obtained by the Landsat-8 satellite. Onboard the Landsat-8 satellite were two sensors, namely operational land imager (OLI) and thermal infrared sensor (TIRS), which help obtain multi-band data in the form of visible and infrared spectra with a fine resolution. We chose Landsat-8 images considering the synchronization of optical and land surface temperature data. The Landsat-8 images were utilized to extract optical data and calculate land surface temperature by the thermal infrared band. In this study, OLI-TIRS Level-1 images, downloaded from the United States Geological Survey (USGS) data archive  by courtesy of the Alaska Satellite Facility (ASF). We chose Sentinel-1 images of the study area based on their acquisition times to ensure that the radar and optical data were approximately synchronous in pairs. The temporally nearest microwave image was selected for each optical image collected already. It was confirmed that the acquisition times of the microwave images were less than five days away from the acquisition times of their optical counterparts. Furthermore, we checked the intervals between the acquisition times of each microwave image and their corresponding optical image to ensure that no precipitation event had occurred during the gaps. Subsequently, the microwave images underwent preprocessing as well. The preprocessing procedures included multi-looking, filtering, topographical correction, geocoding, and radiometric calibration. Finally, the backscattering coefficients in the VH and VV polarization modes of each monitoring site were derived, and the radar incidence angles were recorded.The microwave RS data employed in this study came from the Sentinel-1 satellite. Sentinel-1 provides VH and VV polarization modes C-band images with relatively high spatiotemporal resolution and radiometric accuracy. The imaging data played a crucial part in dynamic hydrological processes and SMC monitoring ,44,45,46http://gdex.cr.usgs.gov/gdex/, accessed on 20 January 2022). The slope data were then derived from DEM using the “Slope” tool integrated into the ArcMap 10.5 software. Both the elevation and slope of each monitoring site were extracted and recorded. We obtained land cover data referring to “Global Land Cover with Fine Classification System at 30 m” (GLC_FCS30) downloaded from http://data.casearth.cn/ (accessed on 20 January 2022). The land cover types of the monitoring sites were collected. Because of the evident attenuation effect of dense vegetation canopies on C-band radar backscattering [The auxiliary data contained a digital elevation model (DEM) and land cover product. This study used DEM from Shuttle Radar Topography Mission (SRTM) downloaded from the USGS website : previous studies have proven the correlation of variation between the SMC and temperature vegetation dryness index (TVDI) ,53. The 3.Elevation and slope: soil moisture was closely related to the local topographical heterogeneity. The landscape shapes physically controlled the hydrological processes and SMC time stability ,58, with4.Land cover type: the land use was analyzed as a factor influencing soil hydraulic attributes and SMC distribution. For example, human activities such as grazing, plowing, and urban development impact the macropores and the continuity of the macropore network of soil, thus altering the mode of local soil water supply and SMC distribution ,61.θ), VH backscattering coefficient (σVH), VV backscattering coefficient (σVV), NDVI, LST, elevation, slope, and land cover type, as inputs of the ANN. The acquisition of the parameters was explained in the previous sections, and we introduced the ordinal number of the data acquisition month to present the data acquisition time for the ANN calculations.By referring to these existing studies, we here selected 9 parameters derived from the RS and auxiliary data, namely the data acquisition time (month), radar incidence angle , which can be expressed as follows:ith sample’s ground-truth and mean ground-truth SMC values of the relevant samples; ith sample’s estimated SMC value and the mean estimated SMC values of all the relevant samples, respectively. The RMSE and r were calculated based on the training, validation, and testing results.The retrieval accuracy was evaluated using 2 statistical metrics: the root-mean-square error (RMSE) and the correlation coefficient (r) values were also given above each plot. The results were promising, with the testing dataset r and overall r reaching 0.85. 3m−3, 0.054 m3m−3, and 0.052 m3m−3 on the training, validation, and testing datasets, respectively. The ground-truth SMC values range from 0.024 to 0.477 m3m−3 with an average value of 0.336 m3m−3, whereas the estimated SMC values ranged from 0.039 to 0.470 m3m−3 with the average value of 0.335 m3m−3. In comparison with the work conducted by Alexakis et al. [r rising from 0.508 to 0.848 and the overall r rising from 0.803 to 0.850.First, the overall accuracy of the ANN was evaluated. All the 635 samples were used and divided into training, validation, and testing datasets. The training/testing process was conducted once, with all nine parameters being involved as the inputs of the ANN  was added as the input parameter, ith sample, ith sample with only basic input parameters as the ANN inputs, and ith sample with a new parameter incorporated into the basic ones as the ANN inputs. ith sample. i samples:The influences of adding data acquisition time on each sample were investigated for further analysis. For each sample participating in SMC retrieval, “accuracy improvement.” In fact, the season or data acquisition time was strongly correlated to the plant growth condition and the corresponding SMC ground-truth data in the vegetation-covered regions. Here, we chose three monitoring sites of which the SMC observations were continuous and long-lasting, and the SMC time series are displayed in Hence, as an input parameter, the data acquisition time contributes to a more delicate description of the vegetation phenological features, and better SMC retrieval outcomes can thus be obtained.r to 0.616 and decrease the RMSE to 0.084 m3m−3.Comparing scenarios 1 and 3: The addition of LST helped increase Sandholt et al.  defined After the addition of LST as the input parameter, for those samples with positive Furthermore, Schmugge  claimed In this study, the ANN managed to retrieve the SMC with higher accuracy with the aid of the LST. This result was further proof for the conclusions made in the studies mentioned above in r-value increased to 0.689, and the RMSE decreased to 0.070 m3m−3. The slope promoted accuracy, with r up to 0.639 and RMSE falling to 0.083 m3m−3. Comparing scenarios 1, 4, and 5: the retrieval accuracy improved remarkably after incorporating the elevation into the input parameter pool. The IiFor further explanation, the accuracy improvement of those samples improving SMC retrieval accuracy  and optical RS data (Landsat-8 images) was demonstrated, and a novel SSE methodology was proposed. With the SSE, the problem of data deficiency due to cloud contamination in optical images and in situ instrument malfunction was resolved. Complete data were fully utilized in the ANN training/testing procedure, and the enlarged sample pool was beneficial to SMC retrieval with high precision. r increased from 0.635 to 0.736, and the RMSE decreased from 0.090 m3m−3 to 0.068 m3m−3. The sample volume could be increased from 264 to 635 by the SSE, and the SMC retrieval accuracy was significantly enhanced. Regarding the average statistical metrics corresponding to 50 ANN training/testing iterations, r-value from 0.588 to 0.689 and the decrease in the RMSE from 0.089 m3m−3 to 0.070 m3m−3. Other parameters were also advantageous to SMC retrieval, except for the land cover type, which barely promoted the accuracy due to the lack of refined land cover categorization. Notably, overall, the SMC retrieval statistical metrics of Scenario 0, where all nine relevant input parameters were considered (the situation “with SSE” discussed in A couple of variables were newly considered about the inputs of ANN for SMC retrieval. As for the sensitivity analysis of the ANN inputs, the parameters, such as the elevation, slope, data acquisition time, LST, and the land cover type, influenced the SMC retrieval accuracy to varying degrees. Among these parameters, the elevation had the most significant impact on the results, as evidenced by the increase in the The study results show that SSE is a promising method for ANN-based SMC retrieval. However, certain limitations need to be addressed. Because study areas overseas are beyond our reach and field surveys on topography and land cover are challenging to implement, the inconsistency between ground truth data and RS data cannot be excluded. The consequent biases in the SMC retrieval are inevitable. Moreover, the SMC mapping lacks additional in situ data for further validation.We plan to focus on sample exploitation over the spatial dimension in the future. In other words, for study areas without sufficient samples for ANN training, synchronous data from another site of geographical resemblance with sufficient samples will be considered for SMC retrieval. The accuracy and conditions for the application of this method will be investigated. Additionally, we intend to utilize state-of-the-art RS data from Chinese satellites, such as GF-3 and GF-1, and explore their applicability in SMC retrieval problems.


To our knowledge, no studies have reported the use of anlotinib in the treatment of locally cancerous nasopharyngeal inverted papillomas that cannot be operated on or treated with radiotherapy. Here, we report a case of a 53-year-old woman diagnosed with recurrent local canceration of nasopharynx papilloma. Magnetic resonance imaging (MRI) showed that the right parapharyngeal space, nasopharynx, and ethmoid sinus were changed, and recurrence was considered. There was no indication for surgery or radiotherapy. Imaging showed that the tumor had obvious enhancement and abundant blood vessels. Immunohistochemistry showed that vascular endothelial growth factor receptor (VEGFR) 2 expression was positive in papilloma tissue and in local canceration tissue of the papilloma. After the patient’s consent was obtained, anlotinib treatment was started in May and ended in November 2019. Then, the patient was treated with intensity-modulated radiotherapy (IMRT) with planning gross tumor volume (PGTV) 66 Gy, planning clinical tumor volume 1 (PCTV1) 60 Gy, and planning clinical tumor volume 2 (PCTV2) 54 Gy in 33 fractions. No disease recurrence was reported at 4 months after radiotherapy. Inverted papilloma (IP) is a benign epithelial tumor of the nasal cavities and paranasal sinuses, and IP of the nasopharynx is rare. IP rates for sinonasal cavity tumors range from 0.4 to 7%. However, three main characteristics make it distinguishable from other sinonasal tumors: its strong invasiveness, high rate of recurrence, and association with carcinoma . StudiesThe reason for recurrent papilloma relapse is unknown. Radiotherapy and surgical resection are the main treatments. However, there is no good method for refractory IP. The early symptoms of NIP malignancy are not typical, and some patients do not pay enough attention to the symptoms. Most of the cases diagnosed as malignant lesions are diagnosed too late. When NIP invades the orbit, the base of the skull, brain tissue, and other parts, radiotherapy and surgical procedures become very difficult, resulting in tumors that are not easy to control. Therefore, it is urgent to develop effective and safe treatments for NIP region cancer patients who cannot undergo surgery or radiotherapy. Anlotinib hydrochloride is a new oral tyrosine kinase inhibitor independently developed in China that has the dual effects of inhibiting tumor angiogenesis and tumor growth , 4. To tA 53-year-old Chinese woman was admitted to the local hospital for repeated right ear pus with hearing loss in November 2016. The examination showed a new growth in the right external auditory meatus and left nasopharyngeal region. However, the patient did not have obvious nasal congestion, dizziness, headache, or other discomfort. Pathology revealed IPs in the nasopharynx and squamous papillary hyperplasia in the external auditory meatus with focal high-grade intraepithelial neoplasia. No distant metastasis was found on chest abdominal computed tomography (CT) or brain MRI. Surgical resection was performed. Since then, due to recurrence of the lesions in the nasopharynx and right ear, the patient underwent three operations in our hospital, and the postoperative pathology showed IP of the nose and papilloma of the middle ear. During this period, there was sometimes pus or bloody secretion in the right ear. On March 21, 2019, the patient went to our hospital again because of nasal obstruction, headache, and dizziness. MRI of the nasopharynx showed that the right parapharyngeal space, nasopharynx, and ethmoid sinus were changed, and the possibility of recurrence was considered  (vs 6.3 months) and PFS (5.4 months vs 1.4 months) were significantly prolonged by the single agent. The incidence of adverse events was similar to that of the control group, and the main adverse reactions were hypertension (64.6%), fatigue (46.3%), increased thyrotropin (44.6%), and hand-foot skin reactions (43.2%).Anlotinib is a new small molecule and multitarget tyrosine kinase inhibitor independently developed in China. It can strongly inhibit angiogenesis-related downstream pathways mediated by VEGFR, fibroblast growth factor receptor (FGFR), and platelet-derived growth factor receptor (PDGFR) and interfere with the proliferation and migration of endothelial cells to form lumen, thereby inhibiting the formation of microvessels, and can interfere with multiple biological processes of tumor cells through inhibition of mast/stem cell growth factor receptor (c-kit) . The inh(c-kit) . At pres(c-kit) , colorec(c-kit) , thyroid(c-kit) , renal c(c-kit) , soft ti(c-kit) , and othIn this case, the local canceration of nasopharynx IP occurred after multiple operations. The recurrence period was short (1–6 months), but there was no viral inclusion body, and HPV infection was not detected by gene sequencing.The patient’s primary tumor invaded the skull base, leading to side effects caused by the large target volume of radiotherapy. Chemotherapy was refused. We analyzed the genes in the tissue and found no common sensitive mutation. The immunohistochemistry results showed that the papilloma tissue and papilloma local canceration tissue were positive for VEGFR2 and that the expression intensities were the same (P < 0.05).VEGFR is highly expressed in many kinds of malignant tumors. However, there are few reports of the high expression of VEGFR2 in papillomas . In factThis case shows that anlotinib provides a new treatment option for locally cancerous nasopharyngeal IP patients who are unable to undergo surgery or radiotherapy. Future clinical research is needed to determine the proportion of patients with NIP malignant transformation and how extensively this kind of patient is represented among those who are treated with anlotinib.The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.PY: writing the article and analyzing the experimental results. GM, YD: pathological results analysis and image collection. QS, CL, and YL: Follow-up of medical records and immunohistochemical test. JL: plan making, publishing funds, article revision. All authors contributed to the article and approved the submitted version.Author YL was employed by company Genecast Biotechnology Co., Ltd.The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


We explored the relationship between the platelet-lymphocyte ratio (PLR), the prognostic nutritional index (PNI), the lactate dehydrogenase-albumin ratio , the controlling nutritional status (CONUT) score, and the long-term survival of colon cancer patients.We conducted a retrospective analysis of the clinical data and follow-up materials of 126 patients with colon cancer who underwent surgical treatment in the Department of Gastrointestinal Surgery of Jiangnan University Affiliated Hospital from June 2012 to December 2015. The receiver operating characteristic curve (ROC) was used to distinguish the high ratio group from the low ratio group. The Kaplan Meier method was used to draw the survival curve in our survival analysis. The log rank test was used for the univariate analysis and the Cox multivariate regression analysis was used to analyze the correlation between preoperative PLR, PNI, LAR, conut scores, and overall survival (OS) and progression free survival (PFS) of patients with colon cancer.P < 0.05).The median follow-up time was 72 months. The OS rates at 3 and 5 years were 83.3% and 78.5%, respectively. The PFS rates at 3 and 5 years were 79.3% and 77.6%, respectively. The 3-year and 5-year OS rates in the low LAR group (≤4.91) were 90.9% and 87.1%, respectively, and were 56.0% and 44.0% in the high LAR group (>4.91) respectively. Univariate and multivariate analyses showed that the LAR value was correlated with OS and PFS (A high preoperative LAR is an independent predictor of the prognosis of colon cancer patients. Colon cancer is one of the most common malignant tumors of the digestive tract. Epidemiological data have shown that colon cancer ranks second in the incidence of malignant tumors in the United States and Europe . In Chinvs albumin ratio  have been used in a variety of cancer prognosis studies (The TNM (tumor-node-metastasis) staging system, traditionally used in clinical practice, is an important way to determine the prognosis of colon cancer, however, we found that clinical outcomes of the patients with the same TNM stage vary from person to person, due to the deficiency of individualized assessment, so our study considers the combination of effective biochemical indicators to analyze their effects on the prognosis of colon cancer patients. At present, it is believed that a patient’s inflammatory response and immune status are related to their therapeutic response and cancer prognosis. The inflammatory response of tumors and the protective immunity of the host are interrelated as a dynamic process, and inflammation can alter this dynamic balance to promote tumorigenesis . Among t studies . It has  studies . The proWe collected data on colon cancer patients who were initially treated for gastrointestinal surgeries at the Affiliated Hospital of Jiangnan University between June 2012 and December 2015. Each patient’s cancer stage was determined using the 2012 International Anti-Cancer Alliance (UICC) 7th Edition Phased Standard with the following criteria: (1) patients with pathologically confirmed primary colon cancer; (2) patients whose serum biochemical examination was performed within 1 week of surgery and had complete data; and (3) patients who underwent radical surgery. The exclusion criteria were as follows: (1) the presence of other primary tumors; (2) patients with acute or chronic inflammatory diseases or infections before surgery; (3) patients with an intestinal obstruction or perforation; (4) patients with severe heart, lung, and kidney diseases; (5) patients who had neoadjuvant treatments such as radiotherapy and chemotherapy performed before surgery. This study was approved by the Medical Ethics Committee of the Affiliated Hospital of Jiangnan University (JNMS01201800138). The data for this retrospective study are anonymous, and the requirement for informed consent was therefore waived.The serum biochemical examination for all patients was performed within 1 week before surgery and the data were complete. The hospital used the SYSMEX blood cell analyzer for blood analysis, and the Roche cobas c702 biochemical instrument to detect liver function and collect laboratory data including platelets, lymphocytes, albumin, cholesterol, and lactic acid dehydrogenase. Treatment of these patients was informed by the 2012 1st edition of the NCCN guidelines: postoperative follow-up observation was used for stage I patients; stage II patients with low-risk factors were treated with capecitabine; patients with high risk factors were treated with 6–8 courses of mFOLFOX adjuvant chemotherapy; and stage III and IV patients were treated with 6–8 courses of mFOLFOX adjuvant chemotherapy. Clinical data, including the patient’s age, gender, tumor site, and TNM stage, were collected from the patient’s disease-history record and pathology report. The laboratory data formula was calculated as follows:9/L) PLR-Platelet count (×109/L)/lymphocyte count (×109/L)PNI-Serum albumin concentration (g/L) + 5× lymphocyte count (×10LAR-Lactic acid dehydrogenase(U/L)/albumin (g/L)The follow-up of survivors was carried out by outpatient reexamination, in-patient reexamination, and telephone and e-mail interviews. The progress follow-up was comprised of a full-body physical examination, an analysis of tumor markers, and a computed tomography (CT) or magnetic resonance imagery (MRI) of the head, chest, abdomen, and pelvis. Follow-up was performed every 3 months for 3 years, and then every 6 months for more than 3 years after surgery. Follow-up was performed annually until December 2020. OS was defined as the time from the day of surgery to the time of death, or until the end of the study. PFS was defined as the time between postoperative pathological diagnosis and a physical examination suggesting the progression to distant metastasis.P-values < 0.05 were considered statistically significant.R software was used to calculate the cutoff value of the PLR, PNI, and LAR, and SPSS 23.0 software was used for the statistical analysis. The Kaplan–Meier method was used to calculate OS and PFS, and the log rank test and the Cox proportional hazards regression model were used for the multivariate analysis. The ROC curve was used to calculate the Youden index (sensitivity + specificity − 1), with patient death as the endpoint. As shown in n = 57), a CONUT2  group , and a CONUT3  group . CONUT Scoring Criteria was shown in The 126 patients with colon cancer were divided into the following three groups according to their nutritional status: a CONUT1  group  and CONUT scores (P < 0.002), but was not statistically significant in correlation with age, gender, T-stage, N staging, clinical staging, PNI, and PLR.The clinical characteristics of 126 patients with colon cancer are shown in The median follow-up time of the patients was 72 months, with OS rates of 83.3% and 78.5% and PFS rates of 79.3% and 77.6% at 3 and 5 years, respectively. The patients were divided into high fraction groups and low fraction groups based on the best critical value. The OS rates in the low LAR group at 3 and 5 years were 90.9% and 87.1%, and those in the high LAR group were 56.0% and 44.0%, respectively.P < 0.01) (see P < 0.01). The OS and PFS of the high LAR group (LAR > 4.91) were lower than those in the group with low LAR (LAR ≤ 4.91), representing a negative correlation (P < 0.01). To better evaluate the prognostic indicators, the gender, N stage, M stage, clinical stage, PLR, and LAR for each patient were included in the Cox multivariate regression model of PFS for analysis. The results showed that gender, clinical stage and LAR were all associated with PFS in patients with colon cancer (P < 0.01) (P < 0.05)  see . In addi < 0.01) . In addi < 0.05) .In this study, the PLR, PNI, LAR, and CONUT score, which are four observation indices representing inflammatory response and immune status, were compared in terms of their ability to determine the prognosis of colon cancer patients. The OS and PFS of patients in the high LAR group were significantly lower than those in the low LAR group. Furthermore, a multivariate analysis showed that the LAR was negatively correlated with the OS and PFS of patients with colon cancer, which was statistically significant. The LAR combines two important indexes: LDH and albumin. During cell metabolism, LDH is a key enzyme that is required for the conversion of pyruvate to lactic acid. Tumor cells proliferate abnormally, consuming large quantities of oxygen in their microenvironment, and rely on anaerobic glycolysis to provide energy to maintain their survival and proliferation. It has been reported that the serum concentration of LDH is reflective of the tumor burden and the degree of hypoxia . Serum ai.e., anti-cancer and cancer-promoting effects, depending on the tumor microenvironment and lymphocyte subtype , and the sensitivity and specificity of the LAR were also better than those of the PLR and the PNI; these findings indicate that the predictive value of the LAR was optimal. In both a univariate and multivariate analysis, the LAR was significantly correlated with the OS and PFS of patients with colon cancer, and can therefore be used as an independent factor to determine the risk of postoperative recurrence and survival in this group. Overall, the LAR had a stronger effect on the prognosis of colon cancer patients than the PLR, the PNI, and CONUT scores. There are several possible reasons for this finding. First, lymphocyte count is a component of the PLR, the PNI, and CONUT scores, and lymphocytes have a bi-directional effect, In previous studies, the optimal cut-off value of the LAR to predict survival was: 5.5 for esophageal cancer , 3.028  for progIn examining the relationship between LAR value and clinical pathological characteristics in colon cancer patients, our results showed a correlation between the LAR and CONUT score. This is consistent because while the CONUT score is a nutritional evaluation index, the LAR itself can better reflect the nutritional status of the whole body. We also found that the LAR is associated with M stages, that patients with stage M1a are more likely to experience an increase in LAR values, and that patients with advanced cancer often experience severe long-term nutritional consumption, which in turn can lead to malnutrition and increase inflammation . In addiIn this study, clinical TNM staging was significantly related to OS and PFS in colon cancer patients both in single-factor and multi-factor analyses. TNM staging has been recognized as a helpful criterion for determining prognosis for malignant tumors. Our study reached a similar conclusion with both the LAR value and clinical staging able to evaluate the survival prognosis of colon cancer patients. The results also show that in a single-factor analysis, M-phased and N-phased are significantly correlated with OS and PFS, whereas in a multi-factor analysis, only M-phased is related to OS, which suggests that a single stage factor is unstable in the prognosis evaluation of colon cancer. We regret that the LAR value was not jointly evaluated with TNM in stages to assess colon cancer prognosis. In further studies, our research team will combine the LAR value and TNM stage to predict and analyze the prognosis of colon cancer patients.In a survival analysis, we found a significant correlation between gender and PFS, with female gender significantly associated with poor prognosis in colon cancer. It is unclear whether the poor prognosis seen in female patients is related to genetic or molecular mechanisms or multiple potential hormones.In conclusion, we found that the LAR value can be used as an independent adverse prognosis factor in patients with colon cancer, and that this prognosis can lead to multi-dimensional risk stratification for these colon cancer patients. These results suggest that we should carry out effective nutritional support before and after surgery; nutrition support can help reduce the toxic side effects of surgical trauma, postoperative chemotherapy, prolong survival, and improve the quality of life of patients. The results also suggest that the follow-up interval of patients should be adjusted according to LAR value, and the follow-up interval of patients with a high LAR value should be shortened to extend their PFS and OS.This study has several limitations. First, it was only a single-center data analysis, and the number of patients (126 cases) may be too small to fully represent all the situations of patients with colon cancer. Our research team aims to conduct a multicenter data analysis with a large sample of prospective studies to further validate the role of the LAR in the assessment of colon cancer prognosis. Second, it was a retrospective study with certain inherent limitations. Third, the survival end point was defined as the death of a patient, and thus the results may differ from those studies that use tumor-related death as the survival end point. Fourth, we only evaluated the LAR at a single point in time prior to surgery. Changes in the LAR over the patient’s entire cancer treatment cycle may have a more significant effect on prognosis, but we did not evaluate that in our study.10.7717/peerj.13091/supp-1Supplemental Information 1Click here for additional data file.


Various diseases caused by food-borne or environmental pathogenic microorganisms have been a persistent threat to public health and global economies. It is necessary to regularly detect microorganisms in food and environment to prevent infection of pathogenic microorganisms. However, most traditional detection methods are expensive, time-consuming, and unfeasible in practice in the absence of sophisticated instruments and trained operators. Point-of-care testing (POCT) can be used to detect microorganisms rapidly on site and greatly improve the efficiency of microbial detection. Lab-on-chip (LOC) is an emerging POCT technology with great potential by integrating most of the experimental steps carried out in the laboratory into a single monolithic device. This review will primarily focus on principles and techniques of LOC for detection of microbial nucleic acid in food and environment, including sample preparation, nucleic acid amplification and sample detection. Pathogenic microorganisms refer to any microorganism capable of injuring its host by competing with it for metabolic resources, destroying its cells or tissues, or secreting toxins. The injurious microorganisms include viruses, bacteria, parasites, fungi, chlamydia, mycoplasma, etc. They can reside in food and the environment  and transmit disease, posing a serious threat to human health . About 4Staphylococcus aureus and E. coli can enter a viable but non-culturable state under severe harsh survival pressure. In this case, these bacteria remain to be harmful because of their virulence and pathogenicity  is carried out in the field of sampling. It can quickly obtain results by using portable analytical instruments, while no professional laboratorians are needed. The development of POCT equipment that can be applied to low-income developing countries should follow the “ASSURED” principles as proposed by the World Health Organization, namely “(1) affordable, (2) sensitive, (3) specific, (4) user-friendly, (5) rapid and robust, (6) equipment-free and (7) deliverable to end-users” . CurrentLab-on-chip, also known as a micro total analysis system, uses microfluidic technology to integrate sample input, dilution, reaction and separation within a single monolithic device. The micro total analytical system was first proposed by A. Maz, N. Gaber and H.M. Idmer in 1990. Based on flow injection analysis, chromatography and electrophoresis, the micro total analytical system can achieve faster and more efficient chromatographic separation, faster electrophoresis separation speed, shorter transmission time, and remarkably reduce the consumption of carrier, reagent or mobile phase A. . Since tin vitro amplification, nucleic acid-based tests can achieve a higher specificity and sensitivity  than immunoassay . CDs has excellent optical properties, so the microspheres have strong fluorescence intensity, good stability and uniformity, and great potential as a fast and sensitive tool for detecting pathogens in milk and other foods. Salmonella monoclonal antibodies for the enrichment of Salmonella Typhimurium from samples. Then they were conjugated with anti-Salmonella polyclonal antibody and catalase modified polystyrene microspheres to form magnetic nanoparticle-bacteria-polystyrene-catalase sandwiches. Catalase from the complex passes through a micromixer to catalyze the decomposition of hydrogen peroxide to produce oxygen. The oxygen increases the pressure in the microchannel and pushes the indicative red dye solution to move along the channel. The movement distance of the red dye can be visually seen using calibration scales and is related to the number of Salmonella typhimurium. In the LOC equipment based on nucleic acid detection, various methods such as magnetophoresis and acoustophoresis are needed to separate the bacteria-microspheres complex from the microspheres without bacteria. After washing and cell lysis, DNA/RNA is obtained for nucleic acid amplification . The results showed that the sensitivity of sample testing of the filtered samples was 100 times higher than that of the unfiltered samples, for the homogenate at a concentration of 102CFU/ml, while the total reaction time from sample preparation to confirmation of E. coli was within 3 h. Filters or membranes can also be used for pathogen enrichment. Salmonella in concentrations as low as 10 pieces/mL from chicken products in less than 1 h. E. coli from physiological samples with high conductivity and viscosity such as milk. In the main channel of the H-type filter, the electrolyte is continuously diffused into the deionized water, while the bacteria remain in the sample. After desalination, the sample is pumped into the DEP chamber, where the bacterial cells are captured through the pDEP. Salmonella serogroups simultaneously. It consists of three microchannels, and in which Salmonella cells are focused on the centerline and guided to the sensing area by pDEP to obtain highly concentrated samples.Dielectrophoresis is a method of separating suspended particles by producing a polarizing force in a non-uniform electric field. The particles in DEP are uncharged but must be polarizable . Large a®Salmonella resistant magnetic beads and Hyglos-Streptavidin magnetic beads) to multiple separate Salmonella typhimurium and E. coli in food preconcentration. The mixed cultures of the bacterial microbead complexes are introduced into the separation chamber with the buffer, and the two types of microbeads are isolated because of different magnetic forces under the influence of the array magnets. E. coli concentration. In this system, E. coli is captured by streptavidin coated magnetic particles (MPs) to form magnetically labeled bacteria (MLBs). The MLBs are suspended in the liquid of the microchannel and are accelerated toward the exit by means of a magnetic field gradient. The magnetic field gradient is generated by the integrated microconductor and controlled by the microcontroller. As a reference, the reference MPs was added to the same liquid in parallel microchannel, and the velocities of MLBs and reference MPs were compared in real time using a digital camera mounted on an optical microscope combined with particle track tracking software.Magnetophoresis is a technology that uses a flexible and controllable magnetic field to manipulate the motion of magnetic beads in a microchannel . The magSalmonella typhimurium from chicken and beef samples by acoustophoresis has achieved high recovery rates (60–90%)  . GN6 aptin vitro (Polymerase chain reaction (PCR) is a molecular biology technique to greatly increase the amount of nucleic acid in vitro . After tin vitro . Digitalin vitro . Reversein vitro . Microflin vitro . A shuntPolymerase chain reaction-based nucleic acid amplification is complex and requires expensive instruments, which does not meet the goals of LOC development. Isothermal nucleic acid amplification is an ideal alternative to PCR given that it is performed at constant temperatures and can be used for nucleic acid amplification without programmable thermal cyclers. In recent years, isothermal nucleic acid amplification technology has been developed rapidly, and the most mature ones include loop-mediated isothermal amplification (LAMP), recombinase polymerase amplification (RPA), helicase-dependent amplification (HDA), rolling circle amplification (RCA), nucleic acid sequence-based amplification (NASBA), cross priming amplification (CPA) , strand Loop-mediated isothermal amplification, which was first proposed by 0–10–1 pg/μL, and the limits of detection of recombinant plasmid DNA was 10–4–10–5 pg/μL. Compared to the conventional microbial detection method, its specificity and sensitivity were 85.53% and 93.52%, respectively. E. coli O157:H7, Staphylococcus aureus, Salmonella, and others in milk samples. Staphylococcus aureus. The entire analysis process took about 4 h and 40 min, and the detection limit was as low as about 27 cells. LAMP has also been used in LOC applications for Vibrio parahaemolyticus in aquatic products, Aspergillus fumigata in clinical and environmental isolates, and Salmonella in food  (Helicase-dependent amplification was first proposed in 2004 by A (tHDA) .E. coli UvrD helicase is used, the methyl directed mismatch repair protein (MUTL protein) should be added to the reaction system. This collaboration between UvrD helicase and MutL protein is associated with the repair of DNA mismatches in E. coli. After the double chain is unchained, the SSB binds to the unchained single chain to prevent recombination of the complementary chains. After stabilizing the DNA, the two primers bind to the target sequence, and DNA polymerase extends the primers using dNTP to produce a double-stranded amplification product  and specificity (100%) (The principle of HDA is shown in  product . Chen ety (100%) .The concept of RCA was first presented in the 1990s , using cE. coli O157:H7, which could significantly improve the detection signal by about 250 times. RCA was used twice in this process. The first RCA was used for in situ amplification of aptamers conjugated to the surface of microchannels. The aptamers are used to capture E. coli O157:H7, and its nucleic acid sequence will be amplified several times by RCA. The target cells captured by RCA amplified microchannels were 3 times more than those without RCA amplified microchannels. The second RCA reaction was aimed to amplify the detection signal of E. coli O157:H7. The product was a long extended repetitive E. coli O157:H7 DNA sequence complementary to the signal probe. The microfluidic platform can be used in a variety of food matrices, including orange juice and milk, with a detection limit of 80 cells/mL.The circular DNA/RNA template is generated by hybridizing primer P with long chain T. Primer P is designed to have a larger and a shorter overlap with T, and the long chain T can be converted into circular molecules by T4 ligase. The RCA reaction for DNA amplification is performed with bacteriophage φ29 DNA polymerase, which has special chain displacement properties. The polymerase begins to synthesize the complementary chain at primer P. After a round of polymerization, it displaces the newly synthesized strand and continues to polymerize, which eventually leads to the formation of a single long strand with a repeating sequence of T . Minero Nucleic acid sequence-dependent amplification is a technique for isothermal RNA amplification firstly proposed by E. coli and Rotavirus in water and Salmonella in pork, beef and milk  hybridizes with the single-stranded RNA to synthesize complementary DNA strands with the action of AMV RT, and then RNase H hydrolyze the RNA strand. The reverse primer (primer 2) hybridizes with the remaining DNA single strand, and the DNA is synthesized to form double stranded DNA with the help of the AMV RT. The T7 RNA polymerase then recognizes the promoter sequence of the DNA and transcribes it into single stranded RNA. In the cyclic phase, single-stranded RNA binds to reverse primers to synthesize single-stranded DNA under the action of AMV RT. The RNA strand in DNA-RNA heterozygote strand will be hydrolyzed by RNase H, and the remaining DNA is hybridized with forward primers to synthesize the DNA sequence with the T7 promoter sequence with the help of AMV RT. T7 RNA polymerase can then use DNA as a template to produce large amounts of single-stranded RNA . Aufdemband milk .Besides pathogen capture, cell lysis, nucleic acid extraction, and nucleic acid amplification, LOC equipment also need a variety of sample testing methods to detect microorganisms qualitatively or quantitatively. Biosensor is a device that measures biological or chemical reactions by producing a signal proportional to the concentration of an analyte. Molecules that specifically recognize the analyte are called biological receptors. The signal generation resulting from the interaction between the biological receptors and the analyte is called biometrics, and mainly in the form of light, heat, pH, charge or mass changes. Most transducers produce optical, electrical, or other measurable signals. These energy signals are then processed and monitored by electronic equipment . SeveralFluorescent probes are often used to detect nucleic acids in real-time PCR . Some nuNucleic acid detection based on CRISPR/Cas system also utilizes fluorescence detection methods. The CRISPR/Cas system is an adaptive immune system which is widely present in bacteria and archaea. It includes three stages: adaptation, expression, and interference. In the adaptation phase, bacteria or archaea carrying one or more CRISPR loci can integrate short DNA fragments homologous to foreign virus or plasmid sequences into host chromosomes. In the expression stage, pre-CrRNA, a primary transcript of the CRISPR gene sequence, is produced and processed into crRNA. crRNA matches the target sequence of the virus or plasmid. In the interference stage, crRNA guides Cas protein to the target sequence of virus or plasmid to form the effector complex, and uses Cas protein to cut the target sequence . NucleicThe principle of Surface plasmon resonance (SPR) is shown in E. coli O157:H7 from food. Aptamer (APT-1) and signaling molecule Rhodamine B (RhB) were bound to gold nanorods (GNRs) to form a gold nanobone (NBs). Apt-1 and RhB were embedded in NBs, and the combination showed good recognition, excellent stability and significant enhancement of Raman signal strength in the detection of E. coli O157: H7.Raman spectra is a kind of scattering spectrum, which can obtain molecular structure information by analyzing the scattering spectrum caused by different incident light frequencies. After the analyte is fixed on the metal surface through interaction with biological receptors, its molecular structure can be identified by Raman spectra. It is found that the intensity of Raman spectra can be greatly improved when the sample is adsorbed on nano-metal particles or metal pieces with rough surface, which is called surface enhanced Raman scattering (SERS) . Yu H. eStaphylococcus aureus and E. coli in food. The system can simultaneously perform nucleic acid amplification and electrochemical detection, and accurately analyze the target pathogen genes by square wave voltammetry (SWV) in 25 s. But before these samples can be used in the developed sensor, DNA must be extracted and purified, which can take a long time. Salmonella, Listeria, and E. coli. This method used a set of specific primers for each pathogen, followed by electrochemical magneto-genosensing on silica magnetic particles. E. coli pathogens.Biological reactions often cause consumption or production of electrons or ions, and the reaction between the receptors and the targets is no exception. The electrical properties of the solution, such as potential and current, may thus change. The transducer can be used to transform the biological signal into a detectable electrical signal proportional to the target concentration . ConductStaphylococcus aureus and E. coli in food integrates nucleic acid amplification and electrochemical detection, but also requires advance DNA extraction and purification. This makes them unable to meet the requirements of POCT. In fact, most LOC equipment used for food and environmental microbiological detection have not yet been integrated with sample processing equipment. Although several techniques have been developed for sample preparation in LOC, including microsphere, filter or membrane, dielectrophoresis, magnetophoresis, acoustophoresis, an equipment that can directly test the obtained samples without sample processing is the ideal LOC. For example, Salmonella in food samples. The entire diagnostic procedure is performed in a single chamber, and up to eight samples can be processed simultaneously. E. coli O157:H7, Listeria monocytogenes and Salmonella enteritidis in milk within 45 min by integrating magnetic bead enrichment target nucleic acid and multiple digital RPA (ImdRPA) into microfluidic chip. Staphylococcus aureus in dairy and meat products. The detection limit was 5 × 100 CFU/mL for milk powder samples and 5 × 101 CFU/mL for pork samples in less than 2 h. The detection time would be greatly reduced if the sample preparation can be integrated into the LOC device  and linear polyacrylamide (LPA), or sealing with bovine serum albumin, are required to mitigate these effects .At present, microfluidics and LOC technologies are booming. With the help of scientists in biology, medicine, chemistry, electronics, materials and other fields, we believe that LOC for nucleic acid detection of food and environmental microorganisms will finally meet the “ASSURED” principles as proposed by WHO, and play an important role in the real-time detection of pathogenic microorganisms in food and environment.YX and ML contributed to study concept and design. LY, WY, FS, MX, ZZ, XB, and JD collected and sorted out literatures. LY, YX, and ML drew pictures. LY, WY, and FS wrote the first draft. YX and ML edited the English version. JD, YX, and ML approved the submitted version after modification. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Introduction: Occupational physicians, as an aspect of the periodic health surveillance of workers prescribed by law, must develop preventive programs against adverse health-related occurrences  to reduce major risk factors for non-communicable/chronic diseases. Eating habits play an important role in defining risk trajectories in the workplace.Methods: We randomly and cross-sectionally evaluated 147 females, of which 59 were healthcare workers (HCWs) and 88 were non-HCWs. The assessment included a dietary screening for adherence to the Mediterranean diet (MD) and a clinical baseline collection of major fluid biomarkers and anthropometric indicators for cardiovascular and metabolic risk.Results: The HCW group exhibited greater adherence to the MD than the non-HCW group. Nevertheless, they showed higher serum levels of triglycerides and total cholesterol. Menopause and type of work significantly and unfavorably affected triglyceride serum levels among HCWs.Conclusion: Greater preventive efforts are needed in the context of periodic health surveillance by occupational physicians. Disseminating additional information on a healthier lifestyle, particularly among female workers of perimenopausal age, is a key issue. The Mediterranean diet (MD) is a diet common to the inhabitants of lands surrounding the Mediterranean Sea, originally observed in Southern Italy in the 1960s and specifically described based on food consumption patterns in the Greek Peninsula . This diAlthough extensive research has consistently provided proof of the numerous beneficial effects of the MD, especially in the context of prevention of CV and metabolic diseases, a shift of the traditional MD pattern toward the so-called “Western diet”  has paradoxically been occurring over the last few decades, even in Mediterranean countries .These changes in Italian eating habits have resulted from a combination of widespread urbanization, globalization and economic crises, at least since the end of the last century, and are often associated with an increase in sedentary work and lifestyle patterns .Thus, from a preventive perspective, the MD should be promoted to a greater extent in Mediterranean countries, especially among individuals of working age. In this regard, the role of occupational physicians is of particular significance, as these professionals are responsible for the management and prevention of diseases related to workplace factors, especially to ensure regular health surveillance of workers exposed to occupational health and safety risks . In addiIndeed, several Italian studies have shown that the promotion of MD in the workplace helps to increase the consumption of whole grains, legumes, white meat and fish and to moderate that of foods rich in cholesterol, saturated fats and sugars . In a saThe objective of this study was to assess possible differences in adherence to the MD and major metabolic and anthropometric parameters between adult female HCWs  and non-HCWs , to determine any association that could help occupational physicians improve preventive health risk management.A transversal observational study was conducted. One hundred forty-seven subjects were randomly recruited at the Operating Unit of Occupational Medicine of the University Polyclinic Hospital of Bari  in the last quarter of 2019. The whole sample included only female employees of public companies with at least 16 years of education and subject to health surveillance by the occupational physicians of the above operating unit, subdivided as follows: 59 HCWs  and 88 employees of other public companies not operating in the field of healthcare (non-HCWs). All the workers were Italian and lived in Puglia. Given that the working schedule of companies employing non-HCWs did not include both day and night shifts, only non-shift HCWs were recruited to avoid the influence of shift work on eating habits and metabolic status . BiologiThe study protocol  met the principles of the Declaration of Helsinki and was approved by the Ethics Committee of the National Cancer Research Center “Giovanni Paolo II,” Bari, Italy. All participants gave informed consent prior to enrollment, in accordance with the Helsinki Declaration of 1964 and subsequent revisions.As part of the periodic health surveillance, a senior physician conducted a cross-sectional evaluation consisting of a brief interview on medical history and lifestyle. Extemporaneous outpatient diastolic blood pressure (DBP) and systolic blood pressure (SBP) were determined in a sitting position after at least a 10-min rest, a minimum of three different times, using an OMRON M6 automatic blood pressure monitor. Subjects with BP values > 130/85 mm Hg or already under drug therapy were classified as currently suffering from hypertension .Metabolic and routine biochemical parameters were closely examined in all subjects. Blood samples were drawn between 08:00 and 09:00 a.m. after overnight fasting. Fasting plasma glucose (FPG), total cholesterol, high- and low-density lipoprotein  cholesterol, and triglyceride (TG) serum levels were assayed. Plasma glucose was determined using the glucose oxidase method , while the concentrations of plasma lipids  were quantified by the automated colorimetric method . LDL cholesterol was directly determined in blood samples. Subjects with circulating LDL cholesterol > 116 mg/dl or already under drug therapy were classified as having hypercholesterolemia .2) and classified according to World Health Organization criteria for normal weight (18.5–24.9 kg/m2), overweight (25.0–29.9 kg/m2), grade I obesity (30.0–34.9 kg/m2), grade II obesity (35.0–39.9 kg/m2), and grade III obesity (≥40.0 kg/m2)  trained for equivalent measuring performances. All anthropometric measurements were taken with participants dressed in lightweight clothing and without shoes. Variables were all collected at the same time between 7:00 and 10:00 a.m. after overnight fasting. Height was measured to the nearest 0.5 cm using a wall-mounted stadiometer . Body weight was determined to the nearest 0.1 kg using a calibrated balance beam scale . BMI was calculated by dividing body weight (kg) by the square of height  administered a previously validated 11-item index, the MedDietScore (MD score) , to asseFor food items presumed to be close to the MD pattern , a score of 0 was assigned when a participant reported no consumption, a score of 1 was assigned for reported consumption of 1–4 times/month, a score of 2 for 5–8 times/month, a score of 3 for 9–12 times/month, a score of 4 for 13–18 times/month and a score of 5 for >18 times/month. In contrast, for the consumption of foods presumed to be inconsistent with this dietary pattern , the opposite scores were assigned . For alcohol consumption, a non-monotonic scoring was adopted based on daily intake of 15–30 g ethanol as suggested by the MD pattern . The resulting total score ranged from 0 to 55.t-test for independent samples. Comparisons of the means of the continuous variables of the stratified women workers based on menopause were performed with ANOVA. Comparisons of the categorical variables were performed with the χ2 test. The averages of total cholesterol, LDL, HDL, TG, SBP and DBP were calculated only for subjects who were not on therapy for hypertension or hypercholesterolemia.Data are reported as the mean ± standard deviation (M ± SD) for continuous measures and frequency and percentage (%) for all categorical variables. The normality of distribution was assessed for each variable using Shapiro's test. Comparisons of the means of the continuous variables between HCWs and non-HCWs were performed with Student's p-value ≤ 0.05 was considered statistically significant, with a 95% confidence interval, and p-values not statistically significant are shown in the tables as “n.s.” All analyses were performed using SPSS Statistics Software.Correlation tests were performed with Pearson's test. A multivariate logistic regression test was performed to calculate the odds ratio (OR). UNIANOVA univariate linear analysis models or two-way variance tests permitted evaluation of the effect of two combined experimental factors to highlight possible interaction effects. By interaction effect, we mean the phenomenon whereby the effect of one factor changes depending on the level of the other factor. A N = 147) featured a majority of non-HCWs (N = 88). p < 0.001) than non-HCWs. Additionally, HCWs consumed significantly higher quantities of red meat and its derivatives, white meat (poultry) and alcoholic beverages (p < 0.001) (The whole sample (< 0.001) .p < 0.05) and between EVOO consumption and LDL cholesterol (p < 0.01). Significant positive correlations were found between TG serum level and age, BMI, and WC (p < 0.001). The same patterns were also found for LDL cholesterol, fasting blood glucose, DBP and SBP.The correlation analysis matrix for the whole sample  showed sp = 0.038) and negatively influenced by EVOO consumption .In the multivariate logistic regression model, LDL cholesterol level > 116 mg/dl was set as the dependent variable, and work category, MD Score > 35, EVOO consumption >/= 5 servings per week (1 serving = 25 ml) were set as the independent variables. The above model showed that LDL cholesterol levels were positively influenced by menopausal status  than the non-HCW group.Differences in categorical variables between the two groups are shown in UNIANOVA analysis was used to assess whether the type of work  or menopausal status could have any effect, singly or in combination, on SBP, DBP, circulating LDL cholesterol, TG serum levels, and fasting blood glucose. We found that menopause had a significant effect on SBP, DBP, LDL cholesterol and blood sugar, regardless of the type of work performed. Higher TG serum levels in HCWs were found to be affected both by menopausal status and type of job .p = 0.012), likely due to the limited dispersion of MD score values relative to the average, as documented by the relatively low standard deviations in both groups.This study shows that HCWs are more MD-adhering than are non-HCWs, as demonstrated by the higher average MD score, implying protection against major non-communicable diseases, perhaps due to their professional knowledge. Despite being arithmetically close, the two averages were significantly different  exhibited higher circulating TG, LDL cholesterol, fasting blood glucose serum level, and blood pressure. Indeed, it is well-known that age, excess weight and visceral adiposity can contribute to increase risks of hypertriglyceridemia, hypercholesterolemia, diabetes and hypertension . In addiFurthermore, the HCW group, including a larger number of subjects in menopause, stands out for higher levels of TG. In this regard, the multivariate logistic regression model and the analysis of two-way variance highlighted that the condition of menopause exerts strong effects on all metabolic fluid biomarkers investigated. In particular, our analyses reveal that menopausal status has a significant adverse effect on TG levels among HCWs. This finding confirms previous evidence supporting the capability of menopause to induce, especially during the transition period, significant metabolic changes that may persist even in late life. Elevated blood lipids, especially LDL cholesterol serum levels, have been recently recorded in both cross-sectional and longitudinal settings . In addiSome limitations of this study should be considered. Because of the cross-sectional approach, it has not been possible to establish the direction of any causal relationship, so our data provide a description rather than an explanation. Prospective studies are needed to clarify causal relationships. In addition, we failed to collect further data on other determinants that may influence the eating habits and metabolic status of female workers, such as marital status, number of children, physical activity, and work-related stress. It would also be interesting to assess shift workers to test whether their eating habits and lifestyle are influenced by work organization and, above all, by night work.Finally, the choice of defining the state of menopause in the anamnestic phase as authoritatively proposed recently by Nelson , withoutIt also should be noted that, although the limited sample size, the study subjects were selected in such a way that the two groups were as homogeneous as possible. In particular, the two groups of female workers were homogeneous in terms of various characteristics capable of influencing metabolic status and lifestyles . Therefore, HCW and non-HCW groups are adequately comparable to ensure a proper statistical analysis of the results. Moreover, according to the formula proposed by Viechtbauer et al., a minimum sample size of 58 subjects is required to perform pilot studies using a 95% confidence interval. The sample under study consisting of 147 female workers, therefore, should be adequate to perform a proper statistical analysis  however HCWs are more adherent to a MD than are non-HCWs, possibly due to greater knowledge of healthy principles related to this dietary pattern. Despite this, HCWs showed higher serum concentrations of triglycerides and total cholesterol. Both menopausal status and type of work were linked to higher TG levels among HCWs.According to the results of the study, the main area of intervention is represented by periodic health surveillance in which the occupational physician will have to propose to the female workers clear and personalized indications on the qualitative and quantitative composition of the diet, also in consideration of the energy expenditure required to carry out the specific tasks.Periodic health surveillance is also an opportunity to better investigate alcohol consumption and look for possible associations with work-related stress factors. This topic could be the subject of future studies.Recent scientific evidence confirms the importance of gender medicine also in the field of occupational medicine. In fact, our results show that the menopause has significant effects on the metabolism and cardiovascular system in women. It is therefore necessary for occupational physicians to develop health promotion programmes specifically aimed at women to counteract the menopausal effects on their health.In addition, to help female workers correct their blood levels of TG and Total Cholesterol, public institutions and private companies should promote their physical activity by entering into agreements with gyms or sports centers and, where possible, by creating jogging and/or walking routes within the company perimeter or by providing suitable company premises with sports equipment . In addition, employers of companies with workplace canteens should require catering companies to provide nutritionally balanced menus, indicating the calories and nutrients in each dish. Another useful intervention would be to introduce low-calorie drinks and snacks in vending machines that are free or low in refined sugars and/or saturated fats and/or salt, respectively. All these interventions should be agreed with the occupational physician and shared with the workers' safety representatives.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Ethics Committee of the National Cancer Research Center Giovanni Paolo II, Bari, Italy . The patients/participants provided their written informed consent to participate in this study.LDi: conceptualization, visualization, and project administration. AP and LV: methodology. AP: software and formal analysis. GD and LV: validation. NM and LL: investigation. GD: resources and supervision. AP, AC, and LDe: data curation. RZ, AP, AC, and LDe: writing—original draft preparation. LDi and GD: writing—review and editing. All authors have read and agreed to the published version of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Tumor promote disease progression by reprogramming their metabolism and that of distal organs, so it is of great clinical significance to study the changes in glucose metabolism at different tumor stages and their effect on glucose metabolism in other organs.18F-FDG PET/CT scans, and the primary lesion SUVmax , liver SUVmean , spleen SUVmean, TLR (Tumor-to-liver SUV ratio) and TSR (Tumor-to-spleen SUV ratio) were included in the study, combined with clinical examination indicators to evaluate DFS .A retrospective single-centre study was conducted on 253 NSCLC  patients with negative lymph nodes and no distant metastasis. According to the AJCC criteria, the patients were divided into different groups based on tumor size: stage IA, less than 3 cm ; stage IB, greater than 3-4 cm ; stage IIA, greater than 4-5 cm ; and stage IIB, greater than 5-7 cm . All of the patients underwent baseline In NSCLC patients, with the increase in the maximum diameter of the tumor, the SUVmax of the primary lesion gradually increased, and the SUVmean of the liver gradually decreased. The primary lesion SUVmax, liver SUVmean, TLR and TSR were related to disease recurrence or death. The best predictive parameters were different when the tumor size differed. SUVmax had the highest efficiency when the tumor size was less than 4 cm  tumor size < 3 cm),  tumor size 3-4 cm), liver SUVmean had the highest efficiency when the tumor size was 4-5 cm ), and TLR had the highest efficiency when the tumor size was 5-7 cm [AUC:0.925 ].In patients with early NSCLC, glucose metabolism reprogramming occurs in the primary lesion and liver. With the increase in tumor size, different metabolic parameters should be selected to evaluate the prognosis of patients. Lung cancer is an important global health problem. In 2020, more than 1.8 million people worldwide died of lung cancer. Non-small cell lung cancer (NSCLC) is particularly aggressive, and even patients with early NSCLC are at risk of death  scan performed to identify lung lesions in our institution within 45 days before surgery. The exclusion criteria were as follows: a) histology other than lung adenocarcinoma or squamous cell carcinoma; b) associated with other cancer types or previous cancer; c) local lymph node positivity or distant metastasis; d) tumor larger than 7 cm; e) Patients with other medical conditions, such as cardiovascular disease, diabetes or liver or spleen disorders; and f) incomplete follow-up information. A total of 10181 patients were selected from the institutional database, and the above inclusion and exclusion criteria were applied to select a cohort of 253 patients. A brief flow diagram is shown in In this retrospective single-centre study, the following inclusion/exclusion criteria were used to select patients from the institutional database. Since studies have shown that positive lymph nodes can affect the survival of patients with NSCLC, we did not include patients with positive lymph nodes , 11. TheAccording to the current 8th edition of the American Joint Committee on Cancer (AJCC) cancer staging manual , the patThe endpoint of this study was DFS, which was defined as the time between the date of surgery and the date of recurrence (event), which refers to tumor recurrence or tumor-related death, or the date of the last visit (after examination). The follow-up period was five years, and recurrence or death within five years was defined as the occurrence of an event. The study was approved by the institutional ethics committee.18F-FDG PET/CT image acquisition was carried out according to version 1.0 of the European Association of Nuclear Medicine (EANM) guidelines on an integrated PET/CT scanner . In short, proper patient preparation (at least 6 hours of fasting) and adequate blood glucose levels (<110 mg/dL) were required. Images were obtained 60 ± 5 minutes after the intravenous injection of 370 MBq/kg of 18F-FDG. First, a low-dose CT scan without contrast enhancement  for a precise anatomical localization and attenuation correction was performed. Next, a three-dimensional PET scan (thickness of 3.27 mm) was performed from the skull base to the proximal thighs with an acquisition time of 3 min per bed position.The PET data sets were iteratively reconstructed using an ordered-subset expectation maximization (OSEM) algorithm with attenuation correction. All collected images were displayed on the GE Healthcare Xeleris 3.0 to reconstruct the PET, CT, and PET/CT fusion images.Two experienced senior nuclear medicine physicians who did not know the clinical information of the patients checked the PET/CT images separately, they all had more than five years of PET/CT diagnostic experience. If the results differed, they discussed the findings and then reached a consensus. According to the PET/CT images, contrast-enhanced CT or magnetic resonance imaging (MRI) was performed when necessary. The region of interest (ROI) for each patient was delineated initially around the tumor outline for the largest cross-sectional area of the primary lung lesion on both the CT and PET images, tumor size was determined at largest cross section. The maximum standardized uptake value (SUVmax) of the primary tumor was measured by carefully placing the ROI on different cross sections of the primary tumor. The mean standardized uptake value (SUVmean) of the liver was measured by selecting a region of interest (ROI) on the axial image. We used the largest cross section of the right lobe of the liver to select a relatively uniform region in the parenchyma of the liver and drew a circle with a diameter not less than 3 cm as the ROI. The liver SUVmean of each patient was measured three times, and the average value was calculated to reduce the selection deviation . Subsequhttp://www.r-project.org) software. All P values less than 0.05 were considered statistically significant.All continuous data are expressed as the mean ± standard deviation, and categorical variables are shown as numbers (percentages). The Kruskal-wallis test was used for continuous variables in the clinical and imaging features, and the Pearson chi-square test or Fisher’s exact test was used for categorical variables as appropriate. Univariate analysis for DFS was performed by the Kaplan-Meier method. The log-rank test and Cox regression analysis were used to identify factors significantly associated with DFS. Time-dependent receiver operating characteristic (timeROC) curve analysis was performed to determine the optimal cut-off and area under the curve (AUC) of primary tumor SUVmax, liver SUVmean, spleen SUVmean, TLR and TSR. Statistical analyses were performed using R   and DFS  and found that there were differences in sex, height, weight, degree of pathological differentiation, fibrinogen (Fib) and thrombin time (TT) between the two groups. In terms of imaging metabolic indexes, there were also differences in primary lesion SUVmax, liver SUVmean, TLR and TSR between the two groups Table 1.Using the imaging and clinical characteristics of all patients to conduct univariate survival analysis, we found that SUVmax, liver SUVmean, differentiation, Fib and so on were prognostic factors of DFS, with AUCs of 0.621 for SUVmax, 0.612 for liver SUVmean, 0.671 for TLR, 0.632 for TSR, 0.525 for pathology, 0.585 for differentiation, 0.523 for TT and 0.602 for Fib Table 2.We analysed the survival risk of imaging metabolic and pathological indexes in the four groups of patients Figure 3Among patients with tumor less than or equal to 3 cm, SUVmax, TLR, TSR and degree of differentiation were related to the risk of DFS. A lower degree of differentiation indicated a higher risk , and higher SUVmax , TLR  and TSR  were also high-risk factors. The cut-off values obtained were 4.6 for SUVmax Figure 4In the analysis of patients with a tumor size of 3-4 cm, it was found that high SUVmax  and TLR  were risk factors for DFS. The cut-off values obtained were 7.69 for SUVmax . The cut-off value we obtained was 2.15  and TSR  were risk factors, and lower liver SUVmean  and degree of differentiation  were high-risk factors for DFS. The cut-off values we obtained were 1.95 for liver SUVmean, 5.89 for TLR, and 6.32 for TSR Figure 6In this study, we evaluated the glucose metabolic changes in primary lesions and their effects on the metabolism of other organs in patients with node-negative NSCLC staged based on tumor size, and we further analysed the correlation between metabolic parameters and prognosis in terms of DFS. We found that with the increase in tumor size, the tumor had an increased glucose metabolism capacity and decreased liver metabolism, and the metabolism of both the primary lesion and the liver were related to disease recurrence. In addition, in the prognosis analysis of tumor of different sizes, we found that different metabolic parameters should be selected to evaluate the prognosis of tumor of different sizes.18F-FDG uptake has been reported as a strong prognostic factor in many malignancies, including lung cancer, lymphoma, cervical cancer, and intrahepatic cholangiocarcinoma (arcinoma , 16–19. arcinoma , 20–22. arcinoma . These s18F-FDG uptake is associated with higher tumor proliferation (18F-FDG PET/CT. We first compared the differences between patients with disease recurrence or death and patients with DFS and found that there were significant differences between the two groups in primary lesion SUVmax, liver SUVmean, TLR and TSR. Univariate and multivariate survival analyses showed that the above four imaging indicators were all associated with DFS. In addition, further stratification of tumor patients according to tumor size showed that SUVmax, TLR and TSR were associated with DFS in groups with tumor sizes less than 3 cm, and SUVmax and TLR were also associated with DFS in patients with tumor sizes of 3-4 cm. This finding was consistent with that of a previous study, which mentioned that 18F-FDG PET had a prognostic cut-off for lung adenocarcinoma in stage IA (In this study, we found that with increasing tumor size, the glucose uptake capacity gradually increased, and the DFS of patients also gradually decreased. As tumors mainly use glycolysis, the increase in glucose metabolism inevitably leads to an increase in glycolytic metabolites. A recent study showed that lactic acid, one of the products of glycolysis, can increase the function of T regulatory cells and inhibit tumor immunity, which may be one of the reasons for the poor survival of patients with higher metabolism . Moreoveferation . We alsostage IA . For patMetabolism is a flexible system that maintains tissue growth and balance, tumor cells in the process of development respond to the external environment and can change their own metabolism, and metabolic changes are rarely limited to the tumor itself. Therefore, to understand the metabolism of cancer, it is necessary to study how the metabolic phenotype evolves over time and how tumor affect the metabolic changes of patients . Many stWith continuous in-depth tumor research, related studies have found that tumor can inhibit the function of immunocytes through glycolysis metabolites , 29. ThiThis study still has some limitations. First, this is a retrospective single-centre study. Further prospective, multicentre, and animal experiment studies should be conducted to verify our findings. Moreover, we did not record the smoking status and lung function of the patients or whether there were specific complications that may affect the DFS of the patients. Because the patients only underwent PET/CT examination one time before the operation, we could not observe the changes in the metabolism of various organs at different stages of the tumor in the same patient. Second, not all patients underwent whole-body PET/CT scans, so we could not investigate the metabolic changes of other organs, such as the kidney. We only studied the changes in glucose metabolism, and other metabolic patterns should also be further studied.Our study found that in patients with early NSCLC, tumor glucose metabolism gradually increases with tumor size and distally regulates the liver and reduces liver metabolism in the primary lesion area, is associated with disease-free survival. When the tumor size is 4-7cm, combining the metabolic levels of remote organs such as the liver and spleen can better predict the prognosis of the patients with NSCLC.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Ethics Committee of the Third Xiangya Hospital. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.HT and MM contributed equally to the literature research, drafting, interpretation, and writing of the manuscript. JH and WZ contributed to the statistics. SH contributed to the collection of patient data. KZ and PR contributed to the design of this work, image interpretation, and writing of the manuscript. All authors contributed to the article and approved the submitted version.This research is supported by the Wisdom Accumulation and Talent Cultivation Project of The Third Xiangya Hospital of Central South University.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.