Objective To evaluate the safety and efficacy of simultaneous resection for initially resectable rectal cancer with synchronous liver metastases. Methods A retrospective analysis was conducted on 305 patients with initially resectable rectal cancer with synchronous liver metastases. These patients were diagnosed at Zhongshan Hospital, Fudan University from January 2016 to June 2020. Among them, 191 underwent simultaneous rectum and liver resection and 114 underwent staged resection. Propensity score matching (PSM) was performed at a 1∶1 ratio. Clinical data were compared and Kaplan-Meier survival curves were plotted. Results After PSM, 85 patients were included in each group. General data showed no significant differences. Except for liver metastasis resection method, no statistical differences were found in primary tumor surgery approach, intraoperative blood loss, intraoperative complications, time to first flatus and defecation, 30-day mortality, and postoperative hospital stay between the simultaneous resection group and the staged resection group. The overall complication rate was higher in the simultaneous resection group (48.2% vs 29.4%, P＝0.04). Specifically, the grade Ⅱ complications were significantly higher (29.4% vs 14.1%, P＝0.016), but there’s no differences in severe complications (grade Ⅲ-Ⅴ). No statistically differences were observed in median progression-free survival (HR＝0.70, 95%CI 0.50-0.97, P＝0.103) and 5-year overall survival (HR＝0.95, 95%CI 0.63-1.44, P＝0.259). Conclusions Simultaneous resection demonstrates comparable safety and efficacy to staged resection for initially resectable rectal cancer with synchronous liver metastases.

Objective:To retrospectively analyze the anesthetic management characteristics of children undergoing resection of pheochromocytoma and paraganglioma (PPGL).Methods:The clinical data from patients undergoing resection of PPGL and confirmed histologically from January 1, 2010 to June 30, 2023 were retrospectively collected. The baseline characteristics, intraoperative conditions and postoperative complications were recorded.Results:The clinical data from 47 pediatric patients were analyzed. The overall incidence of hemodynamic instability events was 68% (32 cases). Lowering preoperative blood pressure to normal levels and the maximum diameter of tumor≥6 cm was helpful in reducing the incidence of the intraoperative hemodynamic instability events ( P<0.05). Postoperative hypotension developed in 7 cases, acute left heart failure in 1 case, arrhythmia in 1 case, adrenocortical insufficiency in 4 cases, and pulmonary infection in 13 cases. Conclusions:Thorough preoperative preparation, evidence-based anesthetic management, and meticulous postoperative vital sign monitoring can increase the perioperative safety for children undergoing resection of PPGL, thereby reducing the incidence of complications.

BACKGROUND:Traumatic spinal cord injury primarily relies on scale assessment and imaging examinations in clinical practice.However,there are limitations in predicting the prognosis of the injury.Therefore,the use of metabolomics technology for biomarker screening is significant for estimating the extent of damage,injury and recovery,as well as developing new therapies. OBJECTIVE:To characterize the metabolic features of patients with traumatic spinal cord injury using metabolomics technology and explore potential biomarkers and disrupted metabolic pathways. METHODS:Serum and urine samples were collected from 20 patients with traumatic spinal cord injury(observation group)and 10 healthy subjects(control group).Metabolites were analyzed and multivariate statistical analysis was then performed for data processing to screen differential metabolites.Metabolic pathway enrichment was performed using MetaboAnalyst software.Logistic regression was applied to construct a biomarker combination model,and its relationship with the American Spinal Injury Association grading was analyzed. RESULTS AND CONCLUSION:Significant differences in 160 and 73 metabolites were detected in the serum and urine samples of the two groups,respectively.Pathway enrichment analysis showed evident disturbances in lipid metabolism after traumatic spinal cord injury,including sphingolipid,arachidonic acid,α-linolenic acid,and arachidonic acid metabolism,as well as glycerophospholipid and inositol phosphate biosynthesis.The combination of two identified biomarkers,telmisartan and quercetin glycoside,showed a correlation with the American Spinal Injury Association grading in both serum and urine levels.Thus,metabolomics technology provides assistance in further understanding the pathological mechanisms of traumatic spinal cord injury and screening therapeutic targets.The identified metabolic biomarker combination may serve as a reference for assessing the severity of traumatic spinal cord injury.

Objective To investigate the expression of Nanog and its regulatory relationship with MMP-2/MMP-9 proteins in esophageal squamous cell carcinoma(ESCC).Methods We detected Nanog and MMP-2/MMP-9 protein expressions in 127 ESCC tissues and 82 adjacent normal tissues using immunohistochemistry and explored their correlations with the clinicopathological parameters and prognosis of the patients.GEO database was utilized to analyze the pathways enriched with the stemness-related molecules including Nanog,and TIMER online tool was used to analyze the correlations among TβR1,MMP-2,and MMP-9 in esophageal cancer.Results Nanog and MMP-2/MMP-9 proteins were significantly upregulated in ESCC tissues and positively intercorrelated.Their expression levels were closely correlated with infiltration depth and lymph node metastasis of ESCC but not with age,gender,or tumor differentiation.The patients with high expressions of Nanog and MMP-2/MMP-9 had significantly shorter survival time.Bioinformatics analysis showed enrichment of stemness-associated molecules in the TGF-β signaling pathway,and the expressions of MMP-2/MMP-9 and TβR1 were positively correlated.In cultured ESCC cells,Nanog knockdown significantly decreased the expression of TβR1,p-Smad2/3,MMP-2,and MMP-9 and strongly inhibited cell migration.Conclusion The high expressions of Nanog,MMP-2,and MMP-9,which are positively correlated,are closely related with invasion depth,lymph node metastasis,and prognosis of ESCC.Nanog regulates the expressions of MMP-2/MMP-9 proteins through the TGF-β signaling pathway,and its high expression promotes migration of ESCC cells.

Objective:To establish a prediction method of diopter based on sequence of ocular biological parameters.Methods:A stratified random cluster sampling method was used to extract the dataset. The dataset consisted of data collected from January 2022 to January 2023 by the Eye & ENT Hospital, Fudan University, from children aged 5 to 13 years in 2 key schools and 2 general schools of Yangpu District, Shanghai. Children’s ocular biological parameters, including sex, age, diopter, axial length, corneal curvature, and anterior chamber depth were collected. The slope of the optimally fitted straight line was calculated using the least squares method. The least square-back propagation (BP) neural network model was established by combining baseline data and the pre-processed rate of the change of ocular biological parameters. The dataset was divided into the training set and the validation set according to the ratio of 8:2 for five-fold cross-validation. The model performance was evaluated by using the mean absolute error (MAE), mean squared error (MSE), root mean square error (RMSE), correlation coefficient R, and coefficient of determination R2. Results:The optimal performances of R2, R, RMSE, MAE, and MSE of the least square-BP neural network model were 0.96, 0.981 9, 0.214 2, 0.139 9 D, 0.045 9, respectively. The regression equation between the predicted value and the true value of the diopter was y=0.97 x+ 0.014 8, R2=0.97, with good correlation. In the internal verification, MAE values of the diopter at three, six, nine, and twelve months of follow-up were 0.110 1, 0.136 0, 0.153 7, and 0.184 8 D, respectively, which achieved clinically acceptable performance (less than 0.25 D). In the external validation, the errors were less than 0.25 D at all ages. Conclusions:A prediction method of diopter based on sequence of ocular biological parameters was successfully developed.

Objective To construct chimeric antigen receptors modified γδT cells targeting at BCMA(BCMA CAR-γδT)and to evaluate its efficacy of anti-multiple myeloma in vitro.Methods Lentiviral vectors containing BCMA single-chain variable fragment were constructed and transiently transfected into 293T cells.The expression of foreign genes was verified by fluorescence microscopy and Western blot;the lentivirus was packaged and the virus titer was determined by flow cytometry.Human peripheral blood αβT cells were infected and γδT cells were examined for its infection efficiency;LDH release method was used to detect the cytotoxic activity of BCMA CAR-γδT cells against human multiple myeloma cell lines in vitro,and the difference of cytotoxic activity between CAR-γδT cells and CAR-αβT cells was compared by Incucyte S3 Live-Cell Analysis Instrument.Results Twenty-four hours after BCMA-CAR lentiviral vector was transferred into 293T cells,the expression of exogenous ZsGreen was microscopied by fluorescence microscope;CD3ζ was detected by Western blot,which showed that BCMA-CAR could be success-fully expressed.The lentivirus was packaged,collected and concentrated(virus titer of 2.23×108 Tu/mL).Infected αβT cells and γδT cells from human peripheral blood in MOI=5,and the results of flow cytometry showed that infection efficiency of αβT cells was 59.18%±2.56%,γδT cells was 48.15±9.86%.The cytotoxic activity of CAR-γδT cells against human myeloma cell lines MM1.S,H929 with high expression of BCMA and K562 cells with over-expression of BCMA was higher than that of empty vector control γδ T cells,which were signifi-cantly enhanced(P＜0.001),but there was no difference in cell lines negative for BCMA expression;Live-Cell Analysis Instrument results showed that the cytotoxic activity of BCMA CAR-γδT cells and BCMA CAR-αβT cells against H929 in vitro was significantly better than their vector control cells.There was no difference in the cytotoxic activities of BCMA CAR-γδT cells as compared with against BCMA negative cell lines,and so do BCMA CAR-T cells.Conclusions Cytotoxic activity of BCMA CAR-γδT targeting at BCMA in vitro was significantly enhanced,which is expected to serve as a novel allogeneic γδT cell product for cell a-doptive immunotherapy of multiple myeloma.

Objective To verify the function of exosomes from 293T cells over-expressing membrane-localized IL-3 in vitro,so as to lay a foundation for in vivo function verification in animal models of Alzheimer's disease.Methods Using the patented structure of the group,a recombinant IL-3 lentiviral vector was constructed and virus-infected 293T cells were packaged.Stable cell strain over-expressing IL-3 was screened.The membrane localization of IL-3 was verified by flow cytometry and immuno-fluorescence.Il-3-exosomes were purified by ultra filtration centrifugation,the exosmic morphology was observed by transmission electron microscope,the size distribution and concentration of exosomes were detected by nano-flow analysis,and the expression of IL-3 and exosome related marker proteins were detected by Western blot.The effect of BV-2 on the phagocytosis of Aβ amyloid was detected by immuno-fluores-cence.Results Through vector construction,virus infection,screening and verification of puromycin,293T cell strain with stable over-expression membrane-anchored IL-3 was obtained.The purified exosomes were collected and the structures of double-layer membrane vesicles with a diameter of 50-100 nm were observed under transmission electron microscope.Western blot results proved the presence of CD63,ALIX,TSG101 and other exosome marker proteins and these molecules were rich in IL-3 as compared with the control,that suggested the successful purifica-tion of IL-3-exosomes.The results of immuno-fluorescence assay showed that IL-3-exosomes promoted the phagocy-tosis of Aβ amyloid by BV-2 cells in vitro.Conclusions The gene modified 293T cell exosomes membrane-anchored expression of IL-3 can play a role of both IL-3 and exosomes in vitro,which promote the phagocytosis of microglia,there for provides a new idea for the clinical treatment of Alzheimer's disease.

Robotic colorectal cancer surgery has rapidly evolved and matured in recent years, with a significant increase in the volume of surgeries and a continuous diversification of surgical types. Increasing high-level evidence indicates that robotic colorectal cancer surgeries, particularly robotic rectal cancer surgeries, significantly accelerate postoperative recovery, reduce the incidence of complica-tions, enhance postoperative quality of life, and decrease rate of positive circumferential resection margins, thereby improving the radical cure rate of the tumor. In recent years, with the rapid develop-ment of medical artificial intelligence (AI) technologies, early explorations such as AI-enhanced surgery and AI autonomous robotic surgeries have also emerged. The authors summarize the develop-ment history, current status, and the application of AI technology in robotic colorectal cancer surgeries.

Objective:To evaluate the optimization effect of ultrasound-guided erector spinae plane block (ESPB)combined with general anesthesia on Nuss procedure in pediatric patients with pectus excavatum undergoing Nuss procedure.Methods:One hundred and eight pediatric patients of either sex, aged 7-18 yr, with body mass index within the normal range, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, undergoing elective Nuss procedure, were randomized into 3 groups ( n=36 each) using a random number table method: ultrasound-guided ESPB combined with general anesthesia group (group E), thoracic epidural anesthesia plus general analgesia group (group T), and general analgesia group (group G). Pediatric patients received ultrasound-guided bilateral ESPB (0.3% ropivacaine was injected, 0.5 ml/kg bilateral total volume [maximum 20 ml]) or thoracic epidural anesthesia (0.3% ropivacaine 0.5 ml/kg [maximum 20 ml/side]) after induction of anesthesia in group E and group T, respectively. All the three groups underwent general anesthesia, anesthesia was induced with propofol 2-3 mg/kg, sufentanil 0.3-0.5 μg/kg and cis-atracurium 0.1-0.2 mg/kg and maintained with propofol 6-10 mg·kg -1·h -1 and remifentanil 0.1-0.3 μg·kg -1·min -1. The patients were endotracheally intubated and mechanically ventilated after anesthesia induction. The parent-controlled intravenous analgesia (PCIA) was used for patients in all the three groups postoperatively. The consumption of intraoperative remifentanil and postoperative consumption of sufentanil for PCIA in each period after surgery were recorded. The time to the first rescue analgesia, consumption of ibuprofen and postoperative complications were also recorded. Results:Compared with group G, the intraoperative consumption of remifentanil and postoperative consumption of sufentanil for PCIA in each period were significantly decreased, the time to the first rescue analgesia was prolonged, and the consumption of ibuprofen was decreased in group E ( P<0.05). There was no significant difference among the three groups ( P>0.05). Conclusions:ESPB combined with general analgesia is helpful in reducing postoperative hyperalgesia in pediatric patients undergoing the Nuss procedure.

Objective:To analyze the current adoption of palliative care by patients with unresectable metastatic colorectal cancer (mCRC) in China.Methods:From 1 March 2023 to 30 June 2023, a questionnaire survey was conducted by random sampling. An exclusive research platform for the Blue Book on Clinical Diagnosis and Treatment of Metastatic Colorectal Cancer. An online questionnaire was sent to medical oncologists (including chief physicians, associate chief physicians, attending physicians and residents) in general hospitals and oncology hospitals in four major regions of East, Central, South and Northeast China. The questionnaire contained 28 questions requesting basic information about doctors, the number of patients with mCRC, the status of treatment from first to fourth line and beyond, points concerning treatment of pain in patients with mCRC, and expectations for the future. A medical team was responsible for the quality control of data collected, whereas statisticians performed the data cleaning and sorting and statistical analysis.Results:A total of 300 clinical questionnaires were collected, including 217 (72%) from doctors in general hospitals and 83 (28%) from doctors in oncology hospitals. Senior physicians (including associate chief physicians and chief physicians) accounted for 65% of the respondents, attending physicians 30%, and residents 5%. Within 3 months (average for each month), 46.4±26.6% patients were diagnosed with recurrent or unresectable mCRC by each physician, 51.6±26.8% of the patients being in cancer hospitals and 44.4±26.3% in general hospitals. One hundred percent of patients receiving first-line treatment received palliative care, as did 80.3% of those receiving second-line treatment, 58.2% of those receiving third-line treatment, and 35.1% of those receiving ≥fourth-line treatment. The primary factor governing selection of first-line treatment was guideline recommendations, whereas comorbidities and the patients' physical status dictated second line to fourth line treatment. Standard first-line treatment was administered to 93.8% of eligible patients, standard second-line treatment to 94.3%; and standard third-line treatment to 73.5%. First-line therapy included targeted therapy in 63.6% of patients and immunotherapy in 2.8%; second-line therapy included targeted therapy in 63.0% of patients and immunotherapy in 2.0%; third-line therapy included targeted therapy in 59.2% of patients and immunotherapy in 2.2%; and fourth-line therapy included targeted therapy in 48.7% of patients and immunotherapy in 3.1%. First-line treatment lasted an average of 9.6 months, second-line treatment 6.7 months, third-line treatment 4.9 months, and fourth-line treatment 3.7 months. More than 70% of the patients maintained a good quality of life after receiving first and second-line treatment and more than 60% of them had ECOG performance scores of 0–1. After receiving third- and fourth-line treatment, 50%–60% of patients maintained a good quality of life and 40%–50% of them maintained ECOG performance scores of 0–1. The survey also revealed that the main deficiencies in treatment were limited effectiveness of third-line treatment, insufficient availability and opportunity for clinical research, popularity of new drugs or new drug combination strategies, and limited channels for participation in multidisciplinary diagnosis and treatment. Clinicians reported looking forward to participating in more clinical research on new drugs, hearing about the experience of experts in the field, and discovery of new targets and new drugs that increased the options for posterior line treatment of colorectal cancer.Conclusions:This report objectively summarizes the current situation, treatment difficulties, and expectations of frontline physicians concerning management of mCRC, thus providing a basis for decision-making and future direction for the diagnosis and research on treatment of mCRC.