Establishing and clinically validating a machine learning model for predicting unplanned reoperation risk in colorectal cancer

BACKGROUND Colorectal cancer significantly impacts global health,with unplanned reoperations post-surgery being key determinants of patient outcomes.Existing predictive models for these reoperations lack precision in integrating complex clinical data.AIM To develop and validate a machine learning model for predicting unplanned reoperation risk in colorectal cancer patients.METHODS Data of patients treated for colorectal cancer(n=2044)at the First Affiliated Hospital of Wenzhou Medical University and Wenzhou Central Hospital from March 2020 to March 2022 were retrospectively collected.Patients were divided into an experimental group(n=60)and a control group(n=1984)according to unplanned reoperation occurrence.Patients were also divided into a training group and a validation group(7:3 ratio).We used three different machine learning methods to screen characteristic variables.A nomogram was created based on multifactor logistic regression,and the model performance was assessed using receiver operating characteristic curve,calibration curve,Hosmer-Lemeshow test,and decision curve analysis.The risk scores of the two groups were calculated and compared to validate the model.RESULTS More patients in the experimental group were≥60 years old,male,and had a history of hypertension,laparotomy,and hypoproteinemia,compared to the control group.Multiple logistic regression analysis confirmed the following as independent risk factors for unplanned reoperation(P<0.05):Prognostic Nutritional Index value,history of laparotomy,hypertension,or stroke,hypoproteinemia,age,tumor-node-metastasis staging,surgical time,gender,and American Society of Anesthesiologists classification.Receiver operating characteristic curve analysis showed that the model had good discrimination and clinical utility.CONCLUSION This study used a machine learning approach to build a model that accurately predicts the risk of postoperative unplanned reoperation in patients with colorectal cancer,which can improve treatment decisions and prognosis.

OPA3 overexpression modulates lipid droplet production and sensitizes colorectal cancer cells to bevacizumab treatment

Background:Colorectal cancer(CRC)represents a substantial risk to public health.Bevacizumab,thefirst US FDA-approved antiangiogenic drug(AAD)for human CRC treatment,faces resistance in patients.The role of lipid metabolism,particularly through OPA3-regulated lipid droplet production,in overcoming this resistance is under investigation.Methods:The protein expression pattern of OPA3 in CRC primary/normal tissues was evaluated by bioinformatics analysis.OPA3-overexpressed SW-480 and HCT-116 cell lines were established,and bevacizumab resistance and OPA3 effects on cell malignancy were examined.OPA3 protein/mRNA expression and lipid droplet-related genes were measured with Western blot and qRT-PCR.OPA3 subcellular localization was detected using immunofluorescence.Proliferation and apoptosis were assessed via colony formation andflow cytometry.Tube formation assays were conducted to assess the angiogenic potential of human umbilical vein endothelial cells(HUVECs).Lipid analysis was used to measure the phosphatidylcholine(PC)and lysophosphatidylcholine(LPC)levels in CRC cells.Results:Bioinformatics analysis revealed that OPA3 was downregulated in CRC.Overexpression of OPA3 inhibited CRC cell proliferation,stimulated apoptosis,and suppressed the angiogenic ability of HUVECs.OPA3 effectively reversed the resistance of CRC cells to bevacizumab and decreased lipid droplet production in CRC cells.Additionally,OPA3 reversed the bevacizumab-induced lipid droplet production in CRC cells,thereby increasing CRC cell sensitivity to bevacizumab treatment.Conclusion:This study suggests that OPA3 modulates lipid metabolism in CRC cells and reduces resistance to bevacizumab in CRC cells.Therefore,OPA3 may be a potential therapeutic target against the AAD resistance in CRC.

Transanal surgery for obstructed defecation syndrome: Literature review and a single-center experience

Obstructed defecation syndrome(ODS) is a functional disorder commonly encountered by colorectal surgeons and gastroenterologists, and greatly affects the quality of life of patients from both societal and psychological aspects. The underlying anatomical and pathophysiological changes of ODS are complex. However, intra-rectal intussusception and rectocele are frequently found in patients with ODS and both are thought to play an important role in the pathogenesis of ODS. With the development of evaluation methods in anorectal physiology laboratories and radiology studies, a great variety of new operative procedures, especially transanal procedures, have been invented to treat ODS. However, no procedure has been proved to be superior to others at present. Each operation has its own merits and defects. Thus, choosing appropriate transanal surgical procedures for the treatment of ODS remains a challenge for all surgeons. This review provides an introduction of the current problems and options for treatment of ODS and a detailed summary of the essential assessments needed for patient evaluation before carrying out transanal surgery. Besides, an overview of the benefits and problems of current transanal surgical procedures for treatment of ODS is summarized in this review. A report of clinical experience of some transanal surgical techniques used in the authors' center is also presented.

Application of nanotechnology in reversing therapeutic resistance and controlling metastasis of colorectal cancer

Colorectal cancer(CRC)is the most common digestive malignancy across the world.Its first-line treatments applied in the routine clinical setting include surgery,chemotherapy,radiotherapy,targeted therapy,and immunotherapy.However,resistance to therapy has been identified as the major clinical challenge that fails the treatment method,leading to recurrence and distant metastasis.An increasing number of studies have been attempting to explore the underlying mechanisms of the resistance of CRC cells to different therapies,which can be summarized into two aspects:(1)The intrinsic characters and adapted alterations of CRC cells before and during treatment that regulate the drug metabolism,drug transport,drug target,and the activation of signaling pathways;and(2)the suppressive features of the tumor microenvironment(TME).To combat the issue of therapeutic resistance,effective strategies are warranted with a focus on the restoration of CRC cells’sensitivity to specific treatments as well as reprogramming impressive TME into stimulatory conditions.To date,nanotechnology seems promising with scope for improvement of drug mobility,treatment efficacy,and reduction of systemic toxicity.The instinctive advantages offered by nanomaterials enable the diversity of loading cargoes to increase drug concentration and targeting specificity,as well as offer a platform for trying the combination of different treatments to eventually prevent tumor recurrence,metastasis,and reversion of therapy resistance.The present review intends to summarize the known mechanisms of CRC resistance to chemotherapy,radiotherapy,immunotherapy,and targeted therapy,as well as the process of metastasis.We have also emphasized the recent application of nanomaterials in combating therapeutic resistance and preventing metastasis either by combining with other treatment approaches or alone.In summary,nanomedicine is an emerging technology with potential for CRC treatment;hence,efforts should be devoted to targeting cancer cells for the restoration of therapeutic sensitivity as well as reprogramming the TME.It is believed that the combined strategy will be beneficial to achieve synergistic outcomes contributing to control and management of CRC in the future.

Cinnamic acid regulates the intestinal microbiome and short-chain fatty acids to treat slow transit constipation

BACKGROUND Slow transit constipation(STC)is a disorder with delayed colonic transit.Cinnamic acid(CA)is an organic acid in natural plants,such as Radix Scrophulariae(Xuan Shen),with low toxicity and biological activities to modulate the intestinal microbiome.AIM To explore the potential effects of CA on the intestinal microbiome and the primary endogenous metabolites-short-chain fatty acids(SCFAs)and evaluate the therapeutic effects of CA in STC.METHODS Loperamide was applied to induce STC in mice.The treatment effects of CA on STC mice were assessed from the 24 h defecations,fecal moisture and intestinal transit rate.The enteric neurotransmitters:5-hydroxytryptamine(5-HT)and vasoactive intestinal peptide(VIP)were determined by the enzyme-linked immunosorbent assay.Hematoxylin-eosin and Alcian blue and Periodic acid Schiff staining were used to evaluate intestinal mucosa's histopathological performance and secretory function.16S rDNA was employed to analyze the composition and abundance of the intestinal microbiome.The SCFAs in stool samples were quantitatively detected by gas chromatography-mass spectrometry.RESULTS CA ameliorated the symptoms of STC and treated STC effectively.CA ameliorated the infiltration of neutrophils and lymphocytes,increased the number of goblet cells and acidic mucus secretion of the mucosa.In addition,CA significantly increased the concentration of 5-HT and reduced VIP.CA significantly improved the diversity and abundance of the beneficial microbiome.Furthermore,the production of SCFAs[including acetic acid(AA),butyric acid(BA),propionic acid(PA)and valeric acid(VA)]was significantly promoted by CA.The changed abundance of Firmicutes,Akkermansia,Lachnoclostridium,Monoglobus,UCG.005,Paenalcaligenes,Psychrobacter and Acinetobacter were involved in the production of AA,BA,PA and VA.CONCLUSION CA could treat STC effectively by ameliorating the composition and abundance of the intestinal microbiome to regulate the production of SCFAs.

Edaravone-loaded poly(amino acid) nanogel inhibits ferroptosis for neuroprotection in cerebral ischemia injury

Neurological injury caused by ischemic stroke is a major cause of permanent disability and death. The currently available neuroprotective drugs fail to achieve desired therapeutic efficacy mainly due to short circulation half-life and poor blood−brain barrier (BBB) permeability. For that, an edaravone-loaded pH/glutathione (pH/GSH) dual-responsive poly(amino acid) nanogel (NG/EDA) was developed to improve the neuroprotection of EDA. The nanogel was triggered by acidic and EDA-induced high-level GSH microenvironments, which enabled the selective and sustained release of EDA at the site of ischemic injury. NG/EDA exhibited a uniform sub-spherical morphology with a mean hydrodynamic diameter of 112.3 ± 8.2 nm. NG/EDA efficiently accumulated at the cerebral ischemic injury site of permanent middle cerebral artery occlusion (pMCAO) mice, showing an efficient BBB crossing feature. Notably, NG/EDA with 50 µM EDA significantly increased neuron survival (29.3%) following oxygen and glucose deprivation by inhibiting ferroptosis. In addition, administering NG/EDA for 7 d significantly reduced infarct volume to 22.2% ± 7.2% and decreased neurobehavioral scores from 9.0 ± 0.6 to 2.0 ± 0.8. Such a pH/GSH dual-responsive nanoplatform might provide a unique and promising modality for neuroprotection in ischemic stroke and other central nervous system diseases.

To explore the pathogenesis of anterior resection syndrome by magnetic resonance imaging rectal defecography

BACKGROUND Over 90%of rectal cancer patients develop low anterior resection syndrome(LARS)after sphincter-preserving resection.The current globally recognized evaluation method has many drawbacks and its subjectivity is too strong,which hinders the research and treatment of LARS.AIM To evaluate the anorectal function after colorectal cancer surgery by quantifying the index of magnetic resonance imaging(MRI)defecography,and pathogenesis of LARS.METHODS We evaluated 34 patients using the standard LARS score,and a new LARS evaluation index was established using the dynamic images of MRI defecography to verify the LARS score.RESULTS In the LARS score model,there were 10(29.41%)mild and 24(70.58%)severe cases of LARS.The comparison of defecation rate between the two groups was 29.36±14.17%versus 46.83±18.62%(P=0.004);and MRI-rectal compliance(MRI-RC)score was 3.63±1.96 versus 7.0±3.21(P=0.001).Severe and mild LARS had significant differences using the two evaluation methods.There was a significant negative correlation between LARS and MRI-RC score(P<0.001),and they had a negative correlation with defecation rate(P=0.028).CONCLUSION MRI defecography and standard LARS score can both be used as an evaluation index to study the pathogenesis of LARS.

Th22 cell accumulation is associated with colorectal cancer development

AIM: To investigate the expression of Th22 cells and related cytokines in colorectal cancer(CRC) tissues, and the probably mechanism.METHODS: CRC tumor and paratumor tissues were collected to detect the expression levels of Th22 cells and of related cytokines by immunohistochemistry, flow cytometry and real-time quantitative polymerase chain reaction(RT-q PCR).Interleukin(IL)-22 alone or with a STAT3 inhibitor was co-cultured with RKO cells in vitro to study the effects of IL-22 on colon cancer cells.IL-22 alone or with a STAT3 inhibitor was injected into a BALB/c nude mouse model with subcutaneously transplanted RKO cells to study the effects of IL-22 on colon cancer growth.RESULTS: The percentage of Th22 cells in the CD4+ T subset was significantly higher in tumor tissues compared with that in paratumor tissues(1.47% ± 0.083% vs 1.23% ± 0.077%, P < 0.05) as determined by flow cytometry.RT-qP CR analysis revealed that the m RNA expression levels of IL-22, aryl hydrocarbon receptor, CCL20 and CCL22 were significantly higher in tumor tissues compared with those in paratumor tissues.CCL27 mR NA also displayed a higher expression level in tumor tissues compared with that in paratumor tissues; however, these levels were not significantly different(2.58 ± 0.93 vs 2.30 ± 0.78, P > 0.05).IL-22 enhanced colon cancer cell proliferation in vitro and displayed anti-apoptotic effects; these effects were blocked by adding a STAT3 inhibitor.IL-22 promoted tumor growth in BALB/c nude mice; however, this effect was reversed by adding a STAT3 inhibitor.CONCLUSION: Th22 cells that accumulate in CRC may be associated with the chemotactic effect of the tumor microenvironment.IL-22 is associated with CRC development, most likely via STAT3 activation.

Combined right hemicolectomy and pancre-aticoduodenectomy for locally advanced right hemicolon cancer

ABSTRACT： Extracolonic invasion of the duodenum and/or pancreatic head rarely occurs in patients with right hemico- Ion cancer. However, when necessary, combined radical op- eration is a challenge to the surgeon. We reported 7 patients with locally advanced right hemicolon cancer who underwent combined right hemicolectomy （RH） and pancreaticoduo- denectomy （PD） due to direct involvement of the duodenum or pancreatic head.

Role of LAP^+CD4^+ T cells in the tumor microenvironment of colorectal cancer

AIM To investigate the abundance and potential functions of LAP^+CD4^+ T cells in colorectal cancer(CRC). METHODS Proportions of LAP^+CD4^+ T cells were examined in peripheral blood and tumor/paratumor tissues of CRC patients and healthy controls using flow cytometry. Expression of phenotypic markers such as forkhead box(Fox)p3, cytotoxic T-lymphocyte-associated protein(CTLA)-4, chemokine CC receptor (CCR)4 and CCR5 was measured using flow cytometry. LAP^-CD4^+ and LAP^+CD4^+ T cells were isolated using a magnetic cellsorting system and cell purity was analyzed by flow cytometry. Real-time quantitative polymerase chain reaction was used to measure expression of cytokines interleukin (IL)-10 and transforming growth factor(TGF)-β.RESULTS The proportion of LAP^+CD4^+ T cells was significantly higher in peripheral blood from patients (9.44% ± 3.18%) than healthy controls (1.49% ± 1.00%, P < 0.001). Among patients, the proportion of LAP^+CD4^+ T cells was significantly higher in tumor tissues(11.76% ± 3.74%) compared with paratumor tissues (3.87% ± 1.64%, P < 0.001). We also observed positive correlations between the proportion of LAP^+CD4^+ T cells and TNM stage(P < 0.001), distant metastasis(P < 0.001) and serum level of carcinoembryonic antigen(P < 0.05). Magnetic-activated cell sorting gave an overall enrichment of LAP^+CD4^+ T cells (95.02% ± 2.87%), which was similar for LAP^-CD4^+ T cells(94.75% ± 2.76%). In contrast to LAP^-CD4^+ T cells, LAP^+CD4^+ T cells showed lower Foxp3 expression but significantly higher levels of CTLA-4, CCR4 and CCR5(P < 0.01). LAP^+CD4^+ T cells expressed significantly larger amounts of IL-10 and TGF-β but lower levels of IL-2, IL-4, IL-17 and interferon-γ, compared with LAPCD4+ T cells.CONCLUSION LAP^+CD4^+ T cells accumulated in the tumor microenvironment of CRC patients and were involved in immune evasion mediated by IL-10 and TGF-β.

Malnutrition and Quality of Life in Chinese Cancer Patients: a Clinical Study of 23,994 Subjects

Background Malnutrition is common in patients with cancer,and can negatively impact their quality of life(QoL)and even survival.However,there is currently no large data available on the prevalence of malnutrition in Chinese cancer patients.This study evaluated the prevalence of malnutrition and the QoL of Chinese patients with locoregional,recurrent or metastatic cancer.Methods We conducted a nationwide observational,multi-center,hospital-based cross-sectional study within the Chinese Society of Nutritional Oncology(CSNO)Network.All of the patients were diagnosed with one of the following 18 different types of malignant tumors:lung cancer,gastric cancer,liver cancer,colorectal cancer,breast cancer,esophageal cancer,cervical cancer,endometrial cancer,nasopharyngeal carcinoma,malignant lymphoma,leukemia,pancreatic cancer,ovarian cancer,prostate cancer,bladder cancer,brain cancer,biliary tract malignant tumors or gastrointestinal stromal tumors.These patients were enrolled from 72 hospitals located in different regions of China.The patients’nutritional status was evaluated based on the body mass index(BMI),loss of bodyweight,laboratory measurements and patient generated-subjective global assessment(PG-SGA)scores.The cancer patients’physical status and QoL were assessed by the Karnofsky Performance Status(KPS)questionnaire and the European Organization for Research and Treatment of Cancer(EORTC)QLQ-C30 questionnaire,respectively.Results From December 2013 to April 2016,23,994 patients hospitalized for cancer treatment(such as surgery,chemotherapy or radiotherapy)were enrolled in the study.The patients included 12,494(52.9%)males and 11,124(47.1%)females.The mean age was 55.8±13.7 years.The proportions of patients in cancer stagesⅠ,Ⅱ,Ⅲ,Ⅳand uncertain were 11.5%,20.3%,27.5%,30.2%and 10.5%,respectively.Among the 23,994 inpatients,the proportions of patients who were underweight(BMI<18.5 kg/m2),normal(18.5 kg/m2<BMI<24 kg/m2),overweight(24 kg/m2≤BMI<28 kg/m2)and obese(BMI≥28 kg/m2)were 9.3%,59.9%,26.1%and 4.7%,respectively.A total of 18.3%(4,101/22,424)of patients had lost 5%or more of their bodyweight within the past month and 19.6%(2,463/12,538)of patients had lost 10%or more of their bodyweight within the past 6 months.According to the PG-SGA scores,26.6%of the patients were severely malnourished(score≥9),31.3%were moderately malnourished(scores 4~8).A total of 22.2%of patients had a serum albumin level lower than 35g/L.Only 8.6%(2056/23,991)of the patients had severe KPS scores(≤60).The patients with these severe KPS scores were most frequently among those with cancers of the brain(19.7%),prostate(18.0%),pancreas(15.5%)and bladder(15.0%).Based on the QLQ-C30 score,11.6%of patients had a poor QoL.The PG-SGA score and global QoL were correlated(r=-0.593,P<0.001).Conclusion The prevalence of malnutrition in patients with cancer is relatively high,and is related to a poorer QoL.The present findings should be kept in mind when assessing cancer patients,because addressing the patient’s problems in nutritional status would be expected to improve both the clinical outcomes and QoL in cancer patients with malnutrition.

Extension Protocol for the Investigation on Nutrition Status and Clinical Outcome of Patients with Common Cancers in China(INSCOC)Study:2021 update

Background Malnutrition is common in patients with cancer,and this adversely affects the survival and quality of life of patients.Chinese Society for Nutritional Oncology issued a multi-center,large-scale,long-term follow-up prospective study,the Investigation on Nutrition Status and Clinical Outcome of Patients with Common Cancers in China(INSCOC study)since 2013.This is an extension to the previous 2013-2020 study protocol.This study still sought to:①address the prognostic impact of nutritional factors and quality of life on cancer patient survival;②describe the overall and cancer-specific incidence and/or distribution of malnutrition and different measurements of patient quality of life.Methods and study design This is an observational,multi-centered,hospital-based prospective cohort study.Data collection will be performed at baseline(within 48 hours after patient admission),during the hospital stay and 30 days after hospital admission.Follow-up will be conducted for 1-20 years after enrollment.The primary outcome will be the all-cause mortality/overall survival,and secondary outcomes will be the length of hospital stay and costs of hospitalization.Study factors will include demographic characteristics,tumor characteristics,information about chronic diseases,hematological measurements(e.g.,red blood cell count,total lymphocyte counts,hemoglobin,albumin,prealbumin,creatinine,C-reactive protein,IL-6),anthropometric measurements(e.g.,height,weight,arm circumference,arm muscle circumference,triceps skinfold thickness,and waist circumference),body composition parameters,PG-SGA scores,quality of life(as indicated by the QLQ-C30 questionnaire),muscle mass(as indicated by the calf circumference),muscle strength(as indicated by the handgrip strength),muscle function(as indicated by the six-meter walking speed test)and physical status assessments(as indicated by the Karnofsky Performance Status scores).This clinical study protocol was approved by local Ethics Committees of all the participating hospitals.Written informed consent is required for each subject included.Discussion This multi-center,large-scale,long-term follow up prospective study will help improve the diagnosis of malnutrition in cancer patients and identify the risk factors associated with adverse clinical outcomes.The anticipated results of this study will highlight the need for a truly scientific appraisal of nutrition therapy in Chinese oncology populations,and finally help treat the potentially reversible elements of malnutrition in cancer patients to improve their clinical outcomes in the future.

Where is the optimal plane to mobilize the anterior rectal wall in female patients undergoing total mesorectal excision?

BACKGROUND Since Heald proposed the total mesorectal excision(TME)procedure,the prognosis of patients with rectal cancer has been significantly improved.But Heald did not specifically describe the anterior surgical plane in female patients.And the surgical plane for mobilizing the anterior rectal wall during TME surgery in female patients remains controversial.AIM To investigate the anatomy of the female pelvis and identify the optimal plane for mobilizing the anterior rectal wall.METHODS We retrospectively collected surgical procedure videos and clinical data of female patients diagnosed with middle or low rectal cancer who underwent the TME procedure between January 2020 and October 2022 across six hospitals.The patients were divided into two groups based on the surgical approach used to mobilize the anterior rectal wall:The experimental group was to open the peritoneum at the lowest point of the peritonea reflection and enter the plane for mobilizing,while the control group was cut at 0.5-1 cm above the peritoneal reflection and enter another plan.Then,we compared the preoperative and postoperative information between the two groups.We also dissected and observed ten adult female pelvises to analyze the anatomic structure and compare the entry plane between the two approaches.Finally,we researched the pathological structure between the rectum and the vagina.RESULTS Finally,77 cases that met the criteria were included in our study.Our observations revealed that the experimental group underwent a smooth procedure,entering the plane amidst the mesorectal fascia and adventitia of the vagina,whereas the control group entered the plane between the vaginal adventitia and muscle layers.Compared to the control group,the experimental group showed a significant decrease in intraoperative bleeding[22.5(19.5-50)mL vs 17(5-20)mL,P=0.01],as well as a shorter duration of hospitalization[9(7-11.25)d vs 7(6-10)d,P=0.03].Through the examination of surgical videos and cadaveric studies,we discovered that Denonvilliers'fascia is absent in females.Additionally,pathological sections further revealed the absence of Denonvilliers'fascia in females,with only loose connective tissue present between the mesorectal fascia and adventitia of the vagina.CONCLUSION The plane amidst the mesorectal fascia and vaginal adventitia is the optimal surgical plane to mobilize the anterior rectal wall for female patients undergoing the TME procedure.

Sex differences in the scored Patient-Generated Subjective Global Assessment in 19,528 cancer patients

Background:The scored Patient-Generated Subjective Global Assessment(PG-SGA)has been widely used to assess the nutritional status of cancer patients.The purpose of this study is to compare the differences in PG-SGA scores and the 7 domain scores of the PG-SGA in male and female cancer patients.Methods:This study was conducted at 72 hospitals from July 2013 to December 2018,a part of the Investigation on Nutritional Status and its Clinical Outcomes of Common Cancers.The PG-SGA was recorded to evaluate the nutritional status of patients.A total of 19,528 patients with 13 common malignancies were included in this study.Student t test and the χ^(2) test were applied to analyze the sex diferences in the 7 domain scores.The Cancer Genome Atlas(TCGA)database was used to analyze the expression levels of symptom-related genes.Results:There were significant sex dfferences in the PG-SGA(P=0.032),notably in patients with gastric cancer(male vs female:9.09±4.86 vs 9.58±5.07,P=0.005)and esophageal cancer(9.64±4.90 vs 10.46±4.96,P=0.011)and the average total PG-SGA of female patients was slightly higher than that of male patients(7.64±4.98 vs 7.77±5.14).The differences were mainly related to the weight,eating,symptom,as well as activity and physical function scores in the stratified analysis.Possible causes of the sex differences were the rates of nausea,vomiting,dry mouth,and other symptoms,in both gastric and esophageal cancer patients.Analysis of the TCGA database suggested that most of the related genes were sex neutral,except for genes related to dysphagia in gastric cancer(VEGFC was higher in female patients,VEGFA and VEGFB higher in male patients).Conclusions:There are sex differences in the PG-SGA scores in patients with various tumor types(female patients generally had higher scores than male patients),with differences mainly in the weight,eating,symptom,as well as activity and physical function scores.The sex differences in PG-SGA scores might be due to the differences in the clinical manifestations of the disease,and further studies should be carried out to investigate other factors influencing the PG-SGA scores in cancer patients.This study provides basic data supporting the individualized nutritional treatment of cancer patients in clinical practice.

Clinical Observation on the Treatment of Pre and Postmenopausal Syndromes by Modified Wumei Decoction

Objective:To compare the efficacy of Wumei Decoction in pre and postmenopausal patients and its effect on follicle-stimulating hormone(FSH)and estradiol(E2).Methods:Sixty-four patients who attended the Department of Traditional Chinese Medicine I in Cangzhou City Central Hospital from January 2020 to January 2022 were selected and randomly divided into treatment group and control group,32 cases in each group.The treatment group took modified Wumei Decoction orally,1 dose of water boiled 2 times a day,divided into 2 warm doses;the control group took Livial orally,2.5 mg/times,1 time/day,and the observation cycles were all for 3 months.Kupperman score,FSH,E2,clinical symptoms and clinical efficacy were compared between the two groups before and after treatment.Results:The Kupperman score of the two groups decreased after treatment,and the difference was statistically significant;the total effective rate of the treatment group was higher than that of the control group,and the difference was statistically significant;there was no statistical significance in the comparison of FSH before and after the treatment of the two groups,but the FSH values of the two groups were significantly lower than those before,and the difference was statistically significant;there was no statistically significant difference in the comparison of E2 of the two groups before treatment,and the E2 values of the two groups were higher than those of the control group after the treatment.After the treatment,E2 of the two groups of patients was significantly higher than before,and the difference was statistically significant.After treatment,E2 of the treatment group was higher than that of the control group,and the comparison between the groups was statistically significant.Conclusion:There was no significant difference between modified Wumei Decoction and Livial in lowering follicle-stimulating hormone levels;modified Wumei Decoction was superior in raising oestradiol;and modified Wumei Decoction was relatively effective in improving clinical symptoms.

Application of modified primary closure of the pelvic floor in laparoscopic extralevator abdominal perineal excision for low rectal cancer

AIM To introduce a novel,modified primary closure technique of laparoscopic extralevator abdominal perineal excision(LELAPE) for low rectal cancer.METHODS We retrospectively analyzed data from 76 patients with rectal cancer who underwent LELAPE from March 2013 to May 2016.Patients were classified into the modified primary closure group(32 patients) and the biological mesh closure group(44 patients).The total operating time,reconstruction time,postoperative stay duration,total cost,postoperative complications and tumor recur-rence were compared.RESULTS All surgery was successfully performed.The pelvic reconstruction time was 14.6 ± 3.7 min for the modified primary closure group,which was significantly longer than that of the biological mesh closure group(7.2 ± 1.9 min,P < 0.001).The total operating time was not different between the two groups(236 ± 20 min vs 248 ± 43 min,P = 0.143).The postoperative hospital stay duration was 8.1 ± 1.9 d,and the total cost was 9297 ± 1260 USD for the modified primary closure group.Notably,both of these categories were significantly lower in this group than those of the biological mesh closure group(P = 0.001 and P = 0.003,respectively).There were no differences observed between groups when comparing other perioperative data,long-term complications or oncological outcomes.CONCLUSION The modified primary closure method for reconstruction of the pelvic floor in LELAPE for low rectal cancer is technically feasible,safe and cost-effective.

Role of Tenascin-X in regulating TGF-β/Smad signaling pathway in pathogenesis of slow transit constipation

BACKGROUND Chronic constipation is a gastrointestinal functional disease that seriously harms physical and mental health and impacts the quality of life of patients.Its incidence rate is 2%-27%.Slow transit constipation(STC)is a common type of chronic functional constipation,accounting for 10.3%-45.5%of such cases.Scholars have performed many studies on the pathogenesis of STC.These studies have indicated that the occurrence of STC may be related to multiple factors,such as dysfunction of the enteric nervous system,interstitial cells of Cajal(ICC)damage,and changes in neurotransmitters regulating intestinal peristalsis.AIM To investigate the role of Tenascin-X(TNX)in regulating the TGF-β/Smad signaling pathway in the pathogenesis of STC.METHODS This study included an experimental group and a control group.The experimental group included 28 patients with severe colonic STC,and the control group included 18 patients with normal colon tissues.Immunohistochemistry(IHC)was used to detect c-Kit,a specific marker of the ICC.Western blot,immunofluorescence,and IHC were used to detect the localization and expression of TNX and TGF-β/Smad.RESULTS IHC showed that the number of ICC with positive c-Kit expression was significantly reduced in the colon of STC patients(22.17±3.28 vs 28.69±3.53,P<0.05)and that the distribution was abnormal.Western blot results showed that c-Kit and Smad7 levels were significantly decreased in the colon of STC patients(c-kit:0.462±0.099 vs 0.783±0.178,P<0.01;Smad7:0.626±0.058 vs 0.799±0.03,P<0.01)and that TNX and Smad2/3 levels were higher in the STC group(TNX:0.868±0.028 vs 0.482±0.032,P<0.01).There was no significant difference in TGF-βbetween the two groups(0.476±0.028 vs 0.511±0.044,P=0.272).Pearson correlation analysis showed that the TNX protein exhibited a strong correlation with Smad2/3 and Smad7(P<0.05,|R|>0.8)and TGF-β(P<0.05,|R|=0.7).CONCLUSION The extracellular matrix protein TNX may activate the TGF-β/Smad signaling pathway by upregulating the Smad 2/3 signaling protein and thereby induce slight or complete epithelial stromal cell transformation,leading to an abnormal distribution and dysfunction of ICC in the diseased colon,which promotes the occurrence and development of STC.

Nomograms for predicting pathological response to neoadjuvant treatments in patients with rectal cancer

BACKGROUND In recent decades, neoadjuvant therapy(NT) has been the standardized treatment for locally advanced rectal cancer(LARC). Approximately 8%-35% of patients with LARC who received NT were reported to have achieved a complete pathological response(pCR). If the pathological response(PR) can be accurately predicted, these patients may not need surgery. In addition, no response after NT implies that the tumor is destructive, resistant to both chemotherapy and radiotherapy, and prone to having a high metastatic potential. Therefore,developing accurate models to predict PR has great clinical significance and can help achieve individualized treatment in LARC patients.AIM To establish nomograms for predicting PR to different NT regimens based on pretreatment parameters for patients with LARC.METHODS Rectal cancer patients were identified from the database of The Sixth Affiliated Hospital, Sun Yat-sen University from January 2012 to December 2016. Logistic regression and nomograms were developed to predict the probability of pCR and good downstaging to ypT0-2N0M0(ypTNM 0-I), respectively, based on pretreatment parameters for all LARC patients. Nomograms were also developed for three NT regimens(capecitabine/deGramont-RT, mFOLFOX6, and m FOLFOX6-RT) to predict pCR probability.RESULTS Four hundred and three patients were included in this study; 72(17.9%) had pCR at the final pathology report, and 177(43.9%) achieved good downstaging to ypT0-2N0M0(ypTNM 0-I). The nomogram for predicting pCR probability showed that NT regimens, tumor differentiation, mesorectal fascia(MRF) status,and tumor length significantly influenced pCR probability. When predicting the probability of good downstaging, tumor differentiation, MRF status, and clinical T stage were the significant factors. Nomograms were developed based on NT regimens. For the capecitabine/de Gramont-RT group, the multivariate analysis showed that the neutrophil-lymphocyte ratio(NLR) was the only significant factor, thus we could not develop a nomogram for this regimen. For the m FOLFOX6-RT group, the analysis showed that the significant factors were tumor length and MRF status; and for the mFOLFOX6 group, the significant factors were tumor length and tumor differentiation.CONCLUSION We established accurate nomograms for predicting the PR to preoperative NT regimens based on pretreatment parameters for LARC patients.

EPR Effect of Amphiphilic Copolymer Micelles Observed by Fluorescent Imaging

Enhanced permeation and retention（EPR） targeting effect of rhodamine B labeled PEG-b-P（LA-co-DHP） [PEG：poly（ethylene glycol）;LA：L-lactide;DHP：2,2-dihydroxylmethyl-propylene carbonate] micelles（RhB-micelles） was observed in H22 liver cancer bearing mice.The RhB-micelles were prepared by conjugating rhodamine B with the DHP units of amphiphilic block copolymer PEG-b-P（LA-co-DHP） followed by subsequent self-assembling of the conjugate.The parent copolymer PEG-b-P（LA-co-DHP） was synthesized by ring-opening copolymerization of LA and DHP with PEG as macroinitiator and diethyl zinc（ZnEt2） as catalyst.The micelles have a spherical shape and the average diameter is ca.50 nm by TEM（transmission electron microscope） or 80 nm by DLS（dynamic light scattering）.Their in vitro cell uptake experiment by CLSM（confocal laser scanning microscopy） and flow cytometry showed preferential internalization of micelles by MCF-7 human breast cancer cells to free RhB.The in vivo tests by live animal imaging and ex vivo excised organ imaging showed that after vena tail injection,free RhB molecules were distributed in the whole body through the circulation system and then gradually metabolized and excreted and there was no preferential partition in tumor bed from the beginning to the end.But the RhB-micelles were preferentially distributed to the tumor bed so that their concentration（fluorescent intensity） in tumor bed got the level of the liver at a certain time point between 1 and 6 h and reached a maximum relative intensity at around 12 h,indicating an obvious EPR effect of RhB-micelles in H22 liver cancer.

Biointerface engineering nanoplatforms for cancer-targeted drug delivery

Over the past decade,nanoparticle-based therapeutic modalities have become promising strategies in cancer therapy.Selective delivery of anticancer drugs to the lesion sites is critical for elimination of the tumor and an improved prognosis.Innovative design and advanced biointerface engineering have promoted the development of various nanocarriers for optimized drug delivery.Keeping in mind the biological framework of the tumormicroenvironment,biomembrane-camouflaged nanoplatforms have been a research focus,reflecting their superiority in cancer targeting.In this review,we summarize the development of various biomimetic cell membrane-camouflaged nanoplatforms for cancertargeted drug delivery,which are classified according to the membranes fromdifferent cells.The challenges and opportunities of the advanced biointerface engineering drug delivery nanosystems in cancer therapy are discussed.