Objective:To evaluate the relationship between preoperative serum bilirubin concentrations and postoperative delirium (POD) in the patients undergoing knee or hip replacement.Methods:Medical records from 413 patients undergoing knee or hip arthroplasty were selected from August 2020 to October 2023 at Qingdao Municipal Hospital using a nested case-control design based on the PNDABLE study cohort. The patients were divided into POD group ( n=77) and non-POD group ( n=336) according to whether POD occurred. Univariate analysis was used to analyze the influencing factors. Logistic regression was used to identify the risk factors for POD. The significance of mediation effect was tested. The receiver operating characteristic curve was drawn to evaluate the accuracy of risk factors in predicting POD. Results:There were significant differences in age, education time, ratio of diabetes history, Memorial Delirium Assessment Scale score, total bilirubin concentration, direct bilirubin concentration, indirect bilirubin concentration, Aβ 42 concentration, p-tau concentration, t-tau concentration, Aβ 42/p-tau ratio and Aβ 42/t-tau ratio between POD group and non-POD group ( P<0.05). The results of logistic regression analysis showed that preoperative serum total bilirubin, direct bilirubin and indirect bilirubin were risk factors for POD ( P<0.05). The results of mediation effects showed that the concentration of total tau protein in CSF partly mediated the relationship between high serum total bilirubin, direct bilirubin and indirect bilirubin concentrations and POD. The area under the receiver operating characteristic curve of total bilirubin, direct bilirubin and indirect bilirubin combined with CSF biomarker concentrations in predicting POD was 0.83 ( P<0.001). Conclusions:Preoperative elevated concentrations of total bilirubin, direct bilirubin and indirect bilirubin are risk factors for POD in the patients undergoing knee or hip replacement. CSF t-tau concentration has a partly mediating role in the association between serum total bilirubin, direct bilirubin and indirect bilirubin concentrations and the development of POD.

Objective:To construct an intelligent endoscopic image analysis system that could monitor the blind spot of the upper gastrointestinal tract, and to test its performance.Methods:A total of 87 167 upper gastrointestinal endoscopy images (dataset 1) including 75 551 for training and 11 616 for testing, and a total of 2 414 pharyngeal images (dataset 2) including 2 233 for training and 181 for testing were retrospectively collected from the Digestive Endoscopy Center of Renmin Hospital of Wuhan University between 2016 to 2020. A 27-category-classification model for blind spot monitoring in the upper gastrointestinal tract (model 1, which distinguished 27 anatomical sites such as the pharynx, esophagus, and stomach) and a 5-category-classification model for blind spot monitoring in the pharynx (model 2, which distinguished palate, posterior pharyngeal wall, larynx, left and right pyriform sinuses) were constructed. The above models were trained and tested based on dataset 1 and 2, respectively, and trained based on the EfficientNet-B4, ResNet50 and VGG16 models of the keras framework. Thirty complete upper gastrointestinal endoscopy videos were retrospectively collected from the Digestive Endoscopy Center of Renmin Hospital of Wuhan University in 2021 to test model 2 blind spot monitoring performance.Results:The cross-sectional comparison results of the accuracy of model 1 in identifying 27 anatomical sites of the upper gastrointestinal tract in images showed that the mean accuracy of EfficientNet-B4, ResNet50, and VGG16 were 90.90%, 90.24%, and 89.22%, respectively, with the EfficientNet-B4 model performance the best, and the accuracy of EfficientNet-B4 model for each site ranged from 80.49% to 97.80%. The cross-sectional comparison results of the accuracy of model 2 in identifying the 5 anatomical sites of the pharynx in the images showed that the mean accuracy of EfficientNet-B4, ResNet50, and VGG16 were 99.40%, 98.56%, and 97.01%, respectively, in which the EfficientNet-B4 model had the best performance, and the accuracy of EfficientNet-B4 model for each site ranged from 96.15% to 100.00%. The overall accuracy of model 2 in identifying the 5 anatomical sites of the pharynx in the video was 97.33% (146/150).Conclusion:The intelligent endoscopic image analysis system based on deep learning can monitor blind spots in the upper gastrointestinal tract, coupled with pharyngeal blind spot monitoring and esophagogastroduodenal blind spot monitoring functions. The system shows high accuracy in both images and videos, which is expected to have a potential role in clinical practice and assisting endoscopists to achieve full observation of the upper gastrointestinal tract.

Lung cancer is the leading cause of cancer death in the world today, and adenocarcinoma is the most common histopathological type of lung cancer. In May 2021, World Health Organization (WHO) released the 5th edition of the WHO classification of thoracic tumors, which classifies invasive non-mucinous adenocarcinoma (INMA) into lepidic adenocarcinoma, acinar adenocarcinoma, papillary adenocarcinoma, solid adenocarcinoma, and micropapillary adenocarcinoma based on its histological characteristics. These five pathological subtypes differ in clinical features, treatment and prognosis. A complete understanding of the characteristics of these subtypes is essential for the clinical diagnosis, treatment options, and prognosis predictions of patients with lung adenocarcinoma, including recurrence and progression. This article will review the grading system, morphology, imaging prediction, lymph node metastasis, surgery, chemotherapy, targeted therapy and immunotherapy of different pathological subtypes of INMA.
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Humans ; Lung Neoplasms/pathology* ; Adenocarcinoma of Lung/pathology* ; Adenocarcinoma/pathology* ; Prognosis ; Lymphatic Metastasis ; Neoplasm Staging ; Retrospective Studies

As the utilization of computed tomography in lung cancer screening becomes more prevalent in the post-pandemic era, the incidence of multiple primary lung cancer (MPLC) has surged in various countries and regions. Despite the continued application of advanced histologic and sequencing technologies in this research field, the differentiation between MPLC and intrapulmonary metastasis (IM) remains challenging. In recent years, the specific mechanisms of genetic and environmental factors in MPLC have gradually come to light. Lobectomy still predominates in the treatment of MPLC, but the observation that tumor-specific sublobar resection has not detrimentally impacted survival appears to be a viable option. With the evolution of paradigms, the amalgamated treatment, primarily surgical, is an emerging trend. Among these, stereotactic ablative radiotherapy (SABR) and lung ablation techniques have emerged as efficacious treatments for early unresectable tumors and control of residual lesions. Furthermore, targeted therapies for driver-positive mutations and immunotherapy have demonstrated promising outcomes in the postoperative adjuvant phase. In this manuscript, we intend to provide an overview of the management of MPLC based on the latest discoveries.
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Humans ; Lung Neoplasms/therapy* ; Early Detection of Cancer ; Lung/surgery* ; Treatment Outcome ; Radiosurgery/methods* ; Neoplasms, Multiple Primary/pathology*

Escherichia coli is a highly adaptable opportunistic pathogen bacterium that can form biofilms on the surface of implants and generates persistent cells,leading to life-threatening infections that are difficult to treat with antibiotics alone.Therefore,there is a need for an effective E.coli biofilm inhibitor to combat this public health threat.Indole is a novel quorum-sensing signaling molecule of E.coli discovered in recent years,which is of great significance in regulating bacterial growth and biofilm formation,and is a potential target for future research on new anti-biofilm preparations.This article reviews the research progress on the formation of Escherichia coli biofilms,the microbial metabolism of indole and its regulation of Escherichia coli biofilm formation,in order to provide information for clinical treatment and drug development.

Objective:To evaluate the relationship between preoperative serum cystatin C (Cys C) concentration and postoperative delirium (POD) in the patients.Methods:Three hundred and ninety patients, aged >50 yr, of American Society of Anesthesiologists Physical Status classification Ⅰor Ⅱ, scheduled for elective knee and hip replacement under combined spinal-epidural anesthesia, with Mini-Mental State Examination scores >23 at 1 day before operation, were included in the study. Peripheral blood samples were collected before operation, and the serum Cys C concentration was measured by the latex-enhanced immunoturbidimetric assay. The cerebrospinal fluid (CSF) 2 ml was collected after successful spinal-epidural puncture for determination of amyloid-β 42 (Aβ42), total tau (T-tau) and phosphorylated tau (P-tau) concentrations by enzyme-linked immunosorbent assay. The patients were divided into POD group and non-POD group according to whether POD occurred. The logistic regression analysis was used to identify the risk and protective factors for POD, and the mediating effect of CSF biomarkers was analyzed. The receiver operating characteristic curve was drawn to evaluate the accuracy of serum Cys C concentration and combination of serum Cys C conceatration and CSF biomarker concentration in predicting POD.Results:Three hundred and twenty-seven patients were finally enrolled, and the incidence of POD was 13.5%. The results of logistic regression showed that increased serum Cys C concentration and increased concentrations of P-tau and T-tau in CSF were risk factors for POD, while increased concentration of Aβ42 and increased Aβ42/P-tau ratio and Aβ42/T-tau ratio in CSF were protective factors for POD ( P<0.05) after adjusting for multiple confounding variables such as age, sex, years of education, Mini-Mental State Examination score, smoking history, drinking history, hypertension and diabetes history. The mediation analysis showed that the relationship between serum Cys C concentration and POD was mediated by T-tau concentration in CSF (11.1%) and by Aβ42/T-tau ratio in CSF (18.0%). The area under the receiver operating characteristic curve of serum Cys C and CSF biomarker concentrations in predicting POD was 0.807 ( P<0.001). Conclusions:Increase in preoperative serum Cys C concentration is a risk factor for POD. T-tau concentration and Aβ42/T-tau ratio in CSF serve as the key mediators in the relationship between preoperative serum Cys C concentration and POD.

Lung cancer, as one of the malignant tumors with the fastest increasing morbidity and mortality in the world, has a serious impact on people's health. With the continuous advancement of medical technology, more and more medical methods are applied to lung cancer screening, which has gradually increased the detection rate of early lung cancer. At present, the standard operation for the treatment of early non-small cell lung cancer (NSCLC) is still lobectomy and mediastinal lymph node dissection. There is a growing trend to use segmentectomy for the treatment of early stage lung cancer. Anatomical segmentectomy not only removes the lesions to the maximum extent, but also preserves the lung function to the greatest extent, and its advantages are also obvious. This article reviews the progress of anatomical segmentectomy in the treatment of early NSCLC.

Objective: To investigate the role of miR-15 a-5 p in DOX resistance of lung cancer cells, and to elucidate the relationship between miR-15 a-5 p and DOX resistance. Methods: miR-15 a-5 p inhibitor and miR-15 a-5 p mimics were used to transfect A549 and A549/DOX resistant cells(A549/D). MTT assay was used to detect cell viability, flow cytometry was used to detect cell apoptosis, Western blot was used to detect the expression of EMT related protein and P53 protein, and QRT PCR was used to detect the expression of miR-15 a-5 p. The potential target genes of miR-15 a-5 p were analyzed by bioinformatics prediction, dual luciferase reporter. A549/D cells were used to establish the xenograft tumor model in nude mice, and the effect of miR-15 a-5 p overexpression on DOX in vivo was analyzed. Results: MTT analysis showed that the knockdown of miR-15 a-5 p increased the cell viability of A549 cells(IC50value: 8.86±0.32 μmol/L), and the overexpression of miR-15 a-5 p decreased the cell viability of A549/D cells(IC50value: 1.92±0.11 μmol/L). Blocking miR-15 a-5 p in A549 cells reduced apoptosis(P<0.001), and increasing the expression of miR-15 a-5 p in A549/D cells promoted apoptosis(P<0.001). The role of DOX in regulating the EMT was reversed by the transfection of miR-451 a inhibitor through Western blot. Bioinformatics prediction showed that there was a specific binding site between P53 and miR-15 a-5 p. miR-15 a-5 p inhibition reduced the expression of P53 protein in A549 cells(P<0.001), and miR-15 a-5 p over-expression increased the expression of P53 protein in A549/D cells(P<0.01). In vivo experiments showed that combination of agomir-miR-15 a-5 p and DOX could reduce the tumor volume and the expression level of N-cadherin, and enhance the expression levels of P53 and E-cadherin. Conclusion miR-15 a-5 p over-expression may inhibit EMT by targeting P53 and enhance the sensitivity of lung cancer cells to DOX therapy.

Objective:To investigate the anticoagulant causes, hemorrhagic susceptibility factors and clinical characteristics of patients with warfarin-related major bleeding in the emergency department of a general hospital.Methods:In a registry study from January 2017 to February 2020, 114 cases of warfarin-related major bleeding patients admitted to Department of Emergency Medicine, the First Affiliated Hospital of Wenzhou Medical University were enrolled. The descriptive methods were used to analyze anticoagulant causes, hemorrhagic susceptibility factors and clinical characteristics. Patients were divided into the international normalized ratio (INR) overrange group and the INR non-overrange group according to INR value during bleeding. The Chi-square test, Student’s t test, and Wilcoxon rank sum test were used to compare the differences between the INR overrange group and the INR non-overrange group. The Wilcoxon rank sum test and Student’s t test were used to analyze the characteristics of gastrointestinal tract bleeding and cerebral hemorrhage. Results:Warfarin-related major bleeding accounted for 0.36% (114/32 040) of first aid cases and 9.84% (114/1 158) of warfarin-taking cases, respectively. Seventy-seven cases (67.5%) of anticoagulant causes were related to atrial fibrillation (AF) and 32 cases (28.1%) were related to post-operative cardiac valve replacement. Of the bleeding susceptibility factors, HAS-BLED scored at 4.0 (3.0, 5.0), 84 cases (73.7%) had a history of drug use, 77 cases (67.5%) aged older than 65 years old, 65 cases (57.0%) had irregular INR monitoring, and 29 cases (25.4%) had recent increase in dose. Forty cases (35.1%) were gastrointestinal tract bleeding with the lowest hemoglobin (Hb) value and the highest score of HAS-BLED. Twenty-one cases (18.4%) were cerebral hemorrhage with the shortest prothrombin time (PT), the lowest INR value, the highest Hb, and the lowest score of HAS-BLED. Twelve cases (10.5%) died or gave up treatment in critical condition, including 6 cases of cerebral hemorrhage, 5 cases of gastrointestinal tract bleeding, and 1 case of hemoptysis. There were statistically significant differences in previous history of antiplatelet therapy, recent increase in dose, HAS-BLED score and bleeding site between the INR overrange group and the INR non-overrange group (all P<0.05). Conclusions:Among patients with warfarin-related major bleeding, AF and post-operative cardiac valve replacement are the main causes of warfarin anticoagulation. INR overrange is related to the previous history of antiplatelet therapy, recent increase in dose, and the high score of HAS-BLED. The gastrointestinal tract bleeding is the most common, with the lowest Hb value and the highest score of HAS-BLED. Cerebral hemorrhage is the second common, with the shortest PT, the lowest INR value, and the highest Hb. The incidence and mortality rates of warfarin-related major bleeding are relatively high.

Objective:To analyze the cause of varicocele (VC) recurrence and investigate the efficacy of sub-inguinal microsurgical varicocelectomy (MV) for recurrent VC.Methods:All of 16 inpatients diagnosed as recurrent VC, in the Department of Andrology of the Affiliated Hospital of Qingdao University from 2015 April to 2019 April, were performed sub-inguinal MV. The age of the inpatients was 18-36 years old, median 27 years old.5 cases were originally performed retroperitoneal high ligation of spermatic vein and other 11 cases were originally performed laparoscopic varicocelectomy. During the review one to three years after the previous operation, all of 16 patients were diagnosed as VC recurrence. The complains of these patients during the review included male subfertility (10 cases) and scrotal pain (12 cases), in which 6 cases’ complains were male subfertility with scrotal pain. After admission, 13 patients were classified as Grade Ⅲ (left in 8 cases, bilateral in 5 cases) and 3 patients as Grade Ⅱ (all left). The median of their visual analogue scale (VAS) was 2.5. Color doppler flow imaging (CDFI) grading showed: Grade Ⅲ in 12 cases (left in 7 cases, bilateral in 5 cases), Grade Ⅱ in 4 cases (all left). Particularly, 12 of them were Graded as Ⅲ simultaneously accompanying with Nut-cracker Phenomenon (NCP). Preoperative tests showed that the average serum testosterone was (16.2±4.9)nmol/ml, the average sperm concentration was (11.8±3.9)×10 6/ml and the progressive motility rate (PR) was (24.4±4.2)%. All of the patients were performed sub-inguinal MV using general anesthesia and supine position. The spermatic cords were clearly exposed and padded up by inserting gauze strips under them. During the operation, the field was magnified 4-6 times with the microscope. Then all of the dilated external and internal spermatic veins were ligated, at the same time the internal spermatic artery and lymph vessels were well preserved. During these operations, 11 patients underwent left-side MV, while other 5 did bilateral MVs. During these MVs, we found twisted and dilated external and internal spermatic veins in all cases and well preserved the internal spermatic arteries and lymph vessels. The number of ligated left and right external spermatic veins were(2.1±0.6) and (1.4±0.5)respectively and the number of ligated left and right internal spermatic veins were (10.1±1.1) and (6.6±0.5) respectively. We also found out(1.3±0.5) internal spermatic arteries and (3.0±1.0)lymph-vessels on left side. On right side, there were (1.4±0.5) internal spermatic arteries and (2.6±0.5) lymph-vessels respectively. At last, we summarily analyzed the pre-operative and post-operative VAS, serum testosterone, CDFI and semen analysis data. Results:All of the 16 sub-inguinal MVs were successfully performed. All patients were reviewed comprehensively 6 months after MV. The reviewed results showed that the post-operative VAS was significantly reduced ( Z=-2.994, P<0.05), palpable scrotal vessels disappeared and Valsalva tests were negative. No obvious reflux of internal spermatic veins were detected by CDFI. Interestingly, the sperm concentration and motility were both significantly improved 6 months after MV ( P<0.05), while there was not remarkable increase of the serum testosterone after MV ( P>0.05). During the follow up, no testicular atrophy, hydrocele and other complications were found. Up to submission, five of the ten patients who presented for male subfertility have impregnated their wives. Conclusions:The most possible cause of VC recurrence could be the omission of the external and internal spermatic veins, particularly in the grade Ⅲ VC patients or VC accompanied with NCP. The sub-inguinal MV, which can discover more twisted spermatic veins and at the same time preserve the spermatic artery and lymph-vessels, shows better clinical efficacy than other procedures.