ObjectiveTo develop a carbon nanoparticle-manganese dioxide (CN-MnO₂) injection integrating visually identifiable staining and magnetic resonance (MR) T₁/T₂ dual-modal imaging, and to systematically evaluate its physicochemical properties, critical quality attributes, biocompatibility, and efficacy for gastrointestinal marking and localization. MethodsCN-MnO₂ was prepared using a mild liquid-phase in situ redox deposition strategy and characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential analysis, X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD). The pH of CN-MnO₂ was directly measured using a pH meter. The osmolality pressure of CN-MnO₂ was determined by the freezing point depression method. The bacterial endotoxin was detected using the gel-clot Limulus amebocyte lysate test, which did not rely on absorbance readings. The appearance of the CN-MnO₂ injection solution stored at 4 ℃ under light shielding and sealed for 0, 5, and 10 days was observed, and its hydrated particle size, polydispersity index, zeta potential, and pH were also measured. With gadopentetate dimeglumine (Gd-DTPA) as the positive control, different concentration gradients were established, and T₁ and T₂ relaxation times were measured to construct concentration-dependent plots of the longitudinal and transverse relaxation rates (R₁ and R₂) and calculate the corresponding relaxivities (r₁ and r₂), compare relaxivity performance, and determine the working concentration for subsequent in vivo experiments. Cytocompatibility was assessed using the methyl thiazolyl tetrazolium (MTT) assay and live/dead staining. Sixteen male 6-week-old SD rats were randomly assigned to an experimental group and a control group (n=8 per group) and subcutaneously injected with CN-MnO₂ injection at a total Mn concentration of 0.80 mmol/L or an equal volume of normal saline, respectively. Short-term in vivo safety was evaluated by regular body weight monitoring, hematoxylin-eosin (HE) staining of major organs, hematological and serum biochemical analyses, inflammatory cytokine detection, and inductively coupled plasma optical emission spectrometry (ICP-OES) analysis. Eight male 5–6-month-old Bama minipigs were randomly assigned to a CN-MnO₂ group (n=6) and a carbon nanoparticle suspension injection (CNSI) group (n=2). CN-MnO₂ injection or CNSI was injected subserosally into the stomach, small intestine, and colon. Within 5 min after each injection, the maximum staining diameter at each injection site was measured and recorded. MR T1WI/T2WI scans were performed on days 3 and 7 after injection to evaluate MR visualization at the injection sites. At the end of observation, the injection sites and major organs were collected for histopathological evaluation by hematoxylin-eosin staining. ResultsCN-MnO₂ appeared as a black suspension, with no obvious aggregation or sedimentation after standing at room temperature (20-25 ℃) for 15 days. Its average hydrodynamic diameter was approximately (228.7±15.3) nm, the polydispersity index was 0.184±0.021, and the zeta potential was (-24.6±2.8) mV. XPS showed that CN-MnO₂ was mainly composed of C, O, and Mn, with oxygen accounting for approximately 68.82%. The Mn 2p spectrum exhibited two characteristic peaks at 642.4 and 653.1 eV. XRD indicated that low-crystallinity δ-MnO₂ was dispersed within the carbon matrix. The pH was 6.82±0.06, the osmolality was (298.4±6.7) mOsm/kg, and the bacterial endotoxin level was below the detection limit. In vitro MR imaging showed a clear concentration-dependent response, with r₁ and r₂ values of 9.6 L·mmol^-1·s^-1 and 17.2 L·mmol^-1·s^-1, respectively, indicating favorable T₁/T₂ contrast performance superior to that of Gd-DTPA. At 0.80 mmol/L, CN-MnO₂ showed no obvious cytotoxicity in vitro. Short-term safety evaluation in SD rats revealed no obvious inflammatory response, impairment of liver or renal function, or abnormal manganese accumulation in major organs. In Bama minipigs, the mean staining diameters of the CN-MnO₂ group in the stomach, small intestine, and colon were (0.65±0.12) cm, (0.61±0.11) cm, and (0.58±0.10) cm, respectively, with no significant difference among the three injection sites (P>0.05). The overall mean staining diameter was smaller in the CN-MnO₂ group than in the CNSI group (P<0.05). MR examinations showed that the injection sites were identifiable on both day 3 and day 7, with stronger signals observed on day 3. At the end of observation, no obvious pathological abnormalities were observed at the injection sites or in major organs. ConclusionA CN-MnO₂ injection with uniform particle size and stable physicochemical properties can be successfully prepared. This formulation integrates visible gastrointestinal staining with MR T₁/T₂ dual-modal imaging, providing a new strategy for preoperative gastrointestinal marking and localization as well as precise intraoperative resection.

Objective:To explore the impact of neoadjuvant immunotherapy on the occurrence of low anterior resection syndrome (LARS) in patients with locally advanced rectal cancer who underwent restorative anterior resection, and to analyze associated risk factors.Methods:This study was an observational study. Patients with adenocarcinoma, mucinous adenocarcinoma, or signet ring cell carcinoma of the rectum located 0-10 cm from the anal verge who received neoadjuvant immunotherapy followed by curative restorative anterior resection at Peking University Cancer Hospital between November 2019 and February 2024 were retrospectively examined. Exclusion criteria were as follows: (1) metastasis detected preoperatively;(2) follow-up <1 year or stoma closure <6 months; (3) local recurrence or metastasis during follow-up; and (4) stoma without closure or stoma re-creation. The Chinese version of the LARS questionnaire was used to assess bowel function by telephone interview, and patients were classified based on score into no LARS (0-20 points), minor LARS (21-29 points), and major LARS (30–42 points). The incidence of LARS, major LARS, and associated risk factors were analyzed.Results:A total of 52 patients (34 men) were included for analysis. Mean age was 58.0 ± 9.8 years and mean body mass index was 25.1 ± 2.6 kg/m 2. Median follow-up was 27.5 months (range, 12.0-63.7). Median LARS score was 21 (range, 1-41). Twenty-six patients (50.0%) developed LARS after surgery, and half of these (13 cases) were classified as major LARS. Stool clustering (repeated defecation within 1 hour) was observed in 80.8% (42/52) of patients. Distance between the tumor edge and the dentate line [odds ratio (OR), 3.597; 95% confidence interval (CI), 1.140-11.360; P=0.026], management of the left colic artery (OR, 0.133; 95% CI, 0.026-0.691; P=0.008), and interval of stoma closure (OR, 5.250; 95%CI, 1.381-19.960; P=0.011) were significantly associated with LARS. Interval of stoma closure was significantly associated with major LARS (OR, 4.200; 95%CI, 1.064–16.584; P=0.040). In multivariate logistic regression, ≤3.5 cm between the tumor edge and the dentate line (OR, 7.407; 95%CI, 1.377-40.000; P=0.020), non-preservation of the left colic artery (OR, 8.403; 95%CI, 1.183-58.823; P=0.033) and interval of stoma closure >6 months (OR, 10.865; 95% CI, 2.039-57.896; P=0.005) were independent risk factors for LARS. Interval of stoma closure >6 months (OR, 4.356; 95% CI, 1.105-17.167; P=0.035) were independent risk factors for major LARS. Conclusion:Patients with locally advanced rectal cancer treated with neoadjuvant immunotherapy experienced a high incidence of LARS after curative surgery, with stool clustering as the predominant symptom. Tumor edge–dentate line distance ≤3.5 cm, non-preservation of the left colic artery, and interval of stoma closure >6 months were risk factors for LARS.

Objective To explore the effect of core muscle stability training combined with biofeedback electrical stimulation on pelvic floor muscle function in postpartum women underwent episiotomy.Methods Clinical data of 98 parturients who underwent selective episiotomy during natural childbirth were retrospectively analyzed.According to different intervention methods,the included parturients were divided into the control group and the combination group,with 49 cases in each group.The control group was treated only with biofeedback electrical stimulation therapy,while the combination group was treated with core muscle stability training combined with biofeedback electrical stimulation therapy.The general information and pelvic floor muscle strength,pelvic floor electromyography values,pelvic floor dysfunction questionnaire(PFDI-20)scores and female sexual function score scale(FSFI)scores were compared between the two groups of parturients before and after intervention.Results There were no significant differences in age,gestational age,body mass index and pelvic floor muscle strength grading between the two groups(P＞0.05).Compared with before intervention,pelvic floor muscle strength,pelvic floor electromyography values and FSFI scores increased in both groups after intervention,while PFDI-20 scores decreased(all P＜0.05).After intervention,compared with the control group,the combination group showed more significant improvement in pelvic floor muscle strength,with an increase in class Ⅰ and class Ⅱ fiber electromyography values,a decrease in PFDI-20 score,and an increase in FSFI scores(all P＜0.05).The incidence of pelvic floor dysfunction in the two groups was statistically significant(22.45%vs.6.12%,P＜0.05).Conclusion Core muscle stability training combined with biofeedback electrical stimulation can effectively promote the recovery of pelvic floor muscle function and improve sexual function in postpartum women underwent episiotomy.

The number of lymph nodes detected in colon cancer is influenced by various factors. The arbitrary application of the 12-lymph node detection threshold as a quality control standard is unreasonable. Overemphasis on the number of lymph nodes may result in an unnecessarily extensive dissection, while existing evidence shows no survival benefit from routine D3 lymphadenectomy. This article systematically reviews the origin, rationale, influencing factors, and common misconceptions surrounding the lymph node detection threshold. It also looks ahead to the trend of narrowing the scope of lymphadenectomy in colon cancer and the potential for personalized dissection strategies.

Objective:To explore the impact of neoadjuvant immunotherapy on the occurrence of low anterior resection syndrome (LARS) in patients with locally advanced rectal cancer who underwent restorative anterior resection, and to analyze associated risk factors.Methods:This study was an observational study. Patients with adenocarcinoma, mucinous adenocarcinoma, or signet ring cell carcinoma of the rectum located 0-10 cm from the anal verge who received neoadjuvant immunotherapy followed by curative restorative anterior resection at Peking University Cancer Hospital between November 2019 and February 2024 were retrospectively examined. Exclusion criteria were as follows: (1) metastasis detected preoperatively;(2) follow-up <1 year or stoma closure <6 months; (3) local recurrence or metastasis during follow-up; and (4) stoma without closure or stoma re-creation. The Chinese version of the LARS questionnaire was used to assess bowel function by telephone interview, and patients were classified based on score into no LARS (0-20 points), minor LARS (21-29 points), and major LARS (30–42 points). The incidence of LARS, major LARS, and associated risk factors were analyzed.Results:A total of 52 patients (34 men) were included for analysis. Mean age was 58.0 ± 9.8 years and mean body mass index was 25.1 ± 2.6 kg/m 2. Median follow-up was 27.5 months (range, 12.0-63.7). Median LARS score was 21 (range, 1-41). Twenty-six patients (50.0%) developed LARS after surgery, and half of these (13 cases) were classified as major LARS. Stool clustering (repeated defecation within 1 hour) was observed in 80.8% (42/52) of patients. Distance between the tumor edge and the dentate line [odds ratio (OR), 3.597; 95% confidence interval (CI), 1.140-11.360; P=0.026], management of the left colic artery (OR, 0.133; 95% CI, 0.026-0.691; P=0.008), and interval of stoma closure (OR, 5.250; 95%CI, 1.381-19.960; P=0.011) were significantly associated with LARS. Interval of stoma closure was significantly associated with major LARS (OR, 4.200; 95%CI, 1.064–16.584; P=0.040). In multivariate logistic regression, ≤3.5 cm between the tumor edge and the dentate line (OR, 7.407; 95%CI, 1.377-40.000; P=0.020), non-preservation of the left colic artery (OR, 8.403; 95%CI, 1.183-58.823; P=0.033) and interval of stoma closure >6 months (OR, 10.865; 95% CI, 2.039-57.896; P=0.005) were independent risk factors for LARS. Interval of stoma closure >6 months (OR, 4.356; 95% CI, 1.105-17.167; P=0.035) were independent risk factors for major LARS. Conclusion:Patients with locally advanced rectal cancer treated with neoadjuvant immunotherapy experienced a high incidence of LARS after curative surgery, with stool clustering as the predominant symptom. Tumor edge–dentate line distance ≤3.5 cm, non-preservation of the left colic artery, and interval of stoma closure >6 months were risk factors for LARS.

Objective To explore the effect of core muscle stability training combined with biofeedback electrical stimulation on pelvic floor muscle function in postpartum women underwent episiotomy.Methods Clinical data of 98 parturients who underwent selective episiotomy during natural childbirth were retrospectively analyzed.According to different intervention methods,the included parturients were divided into the control group and the combination group,with 49 cases in each group.The control group was treated only with biofeedback electrical stimulation therapy,while the combination group was treated with core muscle stability training combined with biofeedback electrical stimulation therapy.The general information and pelvic floor muscle strength,pelvic floor electromyography values,pelvic floor dysfunction questionnaire(PFDI-20)scores and female sexual function score scale(FSFI)scores were compared between the two groups of parturients before and after intervention.Results There were no significant differences in age,gestational age,body mass index and pelvic floor muscle strength grading between the two groups(P＞0.05).Compared with before intervention,pelvic floor muscle strength,pelvic floor electromyography values and FSFI scores increased in both groups after intervention,while PFDI-20 scores decreased(all P＜0.05).After intervention,compared with the control group,the combination group showed more significant improvement in pelvic floor muscle strength,with an increase in class Ⅰ and class Ⅱ fiber electromyography values,a decrease in PFDI-20 score,and an increase in FSFI scores(all P＜0.05).The incidence of pelvic floor dysfunction in the two groups was statistically significant(22.45%vs.6.12%,P＜0.05).Conclusion Core muscle stability training combined with biofeedback electrical stimulation can effectively promote the recovery of pelvic floor muscle function and improve sexual function in postpartum women underwent episiotomy.

The number of lymph nodes detected in colon cancer is influenced by various factors. The arbitrary application of the 12-lymph node detection threshold as a quality control standard is unreasonable. Overemphasis on the number of lymph nodes may result in an unnecessarily extensive dissection, while existing evidence shows no survival benefit from routine D3 lymphadenectomy. This article systematically reviews the origin, rationale, influencing factors, and common misconceptions surrounding the lymph node detection threshold. It also looks ahead to the trend of narrowing the scope of lymphadenectomy in colon cancer and the potential for personalized dissection strategies.

Objective:To investigate the impacts of magnesium isoglycyrrhetinic acid combined with continuous blood purification on organ function and inflammatory mediator levels in patients with severe acute pancreatitis (SAP) complicated with sepsis.Methods:A total of 124 patients with SAP complicated with sepsis who came to Subei People′s Hospital from March 2020 to February 2023 were grouped into an observation group (62 cases) and a control group (62 cases) according to the treatment method, the control group was treated with continuous blood purification, and the observation group was treated with magnesium isoglycyrrhetate on basis of the control group, the organ function, inflammatory mediator levels, clinical efficacy, and clinical medication safety of two groups were compared.Results:After treatment, the scores of acute physiology and chronic health status assessment (APACHE) Ⅱ and sequential organ failure assessment (SOFA) in both groups were decreased compared to before treatment, and the scores of APACHE Ⅱ and SOFA in the the observation group were lower than those in the control group: (26.43 ± 3.78) scores vs. (35.99 ± 3.87) scores, (9.18 ± 1.52) scores vs. (14.51 ± 1.88) scores, there were statistical differences ( P<0.05). After treatment, the levels of interleukin (IL)-8, tumor necrosis factor-α (TNF-α) and IL-6 in both groups were decreased, and the levels of IL-8, TNF-α and IL-6 in the the observation group were lower than those in the control group: (114.81 ± 23.74) ng/L vs.(268.32 ± 29.14) ng/L, (214.41 ± 25.09) ng/L vs. (311.33 ± 28.11) ng/L, (32.58 ± 4.76) ng/L vs. (46.35 ± 5.76) ng/L, there were statistical differences ( P<0.05). The total clinical effective rate after treatment in the the observation group was higher than that in the control group: 96.77%(60/62) vs. 80.65%(50/62), there was statistical difference ( χ2 = 6.52, P<0.05). The incidence of adverse reactions in the two groups had no statistical difference ( χ2 = 0.08, P>0.05). Conclusions:Magnesium isoglycyrrhetinic acid combined with continuous blood purification can improve organ function and reduce inflammatory mediator levels in SAP patients with sepsis.

Background and Aims:Preventive temporary stoma has been widely used in surgeries for rectal cancer as a simple and effective method to reduce the severity of postoperative anastomotic leakage.However,some patients with preventive temporary stomas cannot undergo reversal due to various factors,resulting in a permanent stoma.Permanent stomas remain a common adverse outcome in clinical practice,and the reasons behind this are not entirely clear.This study analyzes a continuous surgical sample from a single center to explore the risk factors for forming permanent stoma. Methods:The clinical data of patients who underwent anal-preserving rectal cancer surgery with preventive temporary stoma in Gastrointestinal Cancer Center Ⅲ of Peking University Cancer Hospital from January 2020 to March 2023,with over 12 months of follow-up,were retrospectively collected.The occurrence of permanent stoma was analyzed,and the clinical variables of patients with permanent stoma were compared to those who underwent stoma reversal,along with an analysis of the risk factors for permanent stoma formation.Permanent stoma was defined as ostomy reversal failure for more than 12 months. Results:A total of 299 patients were included,among which 268(89.63％)underwent stoma reversal(stoma closure group),and 31(10.37％)did not(permanent stoma group).Compared to the stoma closure group,the permanent stoma group had a higher incidence of distant organ metastasis at diagnosis(7.5％vs.25.85％,P=0.003)and also had higher proportions of T3 and T4 stages,N2 stage,and clinical stage Ⅳ(all P＜0.05)with an elevated overall postoperative complication rate(19.0％vs.41.9％,P=0.003)as well as a higher rate of severe complications(1.1％vs.9.7％,P=0.016)and an increased incidence of anastomotic leakage(4.9％vs.19.4％,P=0.006).Logistic regression analysis revealed that the presence of distant organ metastasis at diagnosis(OR=5.41,95％CI=1.80-16.27,P=0.003),and occurrence of anastomotic leakage(OR=4.44,95％CI=1.15-17.09,P=0.030)were independent risk factors for the formation of permanent stomas. Conclusion:At present,some patients still cannot undergo reversal of their preventive temporary stoma,resulting in permanent stoma.The formation of permanent stomas is closely related to a low tumor location,distant organ metastasis at diagnosis,and the occurrence of anastomotic leakage.

Objective:To investigate the value of early tight junction protein Claudin-5 levels in predicting the severity of acute pancreatitis (AP).Methods:A prospective observational study was conducted, including patients diagnosed with AP and admitted to the Northern Jiangsu People's Hospital from December 1, 2021 to November 30, 2022. Eligible healthy volunteers were randomly selected to serve as healthy controls during the same period. Patients were classified into mild acute pancreatitis (MAP) group, moderate-severe acute pancreatitis (MSAP) group, and severe acute pancreatitis (SAP) group based on the 2012 Atlanta classification criteria. Patients with SAP were then divided into three subgroups of 1, 3, and 7 days based on the duration of hospitalization. Baseline data, such as gender, age, underlying disease, and probable etiology, was collected from all enrolled individuals. The enzyme-linked immunosorbent assay (ELISA) was employed to detect serum Claudin-5 levels in each cohort of enrollees. Data on additional serologic indicators, including hematocrit (HCT), albumin (Alb), serum Ca 2+, C-reactive protein (CRP), and procalcitonin (PCT) levels, were obtained via the in-hospital test query system in each group of patients with AP. The modified Marshall score (mMarshall), modified CT severity index (mCTSI) score, bedside severity index of severity in acute pancreatitis (BISAP) score, and acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) were recorded for each group of patients with AP. Differences in the above indicators between groups were analyzed and compared. Spearman's correlation method was employed to examine the relationship between Claudin-5 levels and each influential factor. The receiver operator characteristic curve (ROC curve) was plotted to analyze the predictive value of each influencing factor on SAP. Ridge regression was used to screen for independent risk factors for SAP. Results:A total of 109 patients with AP were enrolled, comprising 66 in the MAP group, 15 in the MSAP group, and 28 in the SAP group. Additionally, 27 healthy volunteers were enrolled as the healthy control group. No statistically significant differences were observed in gender and age among the enrolled groups, and no statistically significant differences were identified among the three groups of patients with AP in terms of underlying disease and etiologic composition. As the disease progressed, serum Claudin-5 levels exhibited a notable increase across all AP patient groups, and they were all significantly higher than those in the healthy control group [ng/L: 888.58 (574.52, 1 141.59), 3 749.02 (2 784.93, 5 789.92), 4 667.81 (3 935.21, 7 315.66) vs. 291.13 (250.19, 314.75), all P < 0.05]. Subgroup analyses showed that as the disease duration prolonged, patients in the SAP group exhibited a notable decline in Claudin-5 levels at 3 days post-admission, compared with those at 1 day post-admission [ng/L: 2 052.59 (1 089.43, 4 006.47) vs. 4 667.81 (3 935.21, 7 315.66), P < 0.05]. Spearman correlation analysis showed that serum Claudin-5 levels in patients with AP were significantly positively correlated with CRP, PCT, HCT, and mMarshall, mCTSI, and BISAP scores ( r values were 0.570, 0.525, 0.323, 0.774, 0.670, 0.652, all P < 0.001), and significantly negatively correlated with Alb ( r = -0.394, P < 0.001). A significant trend was observed in patients with AP, with an increase of HCT levels and a decrease of Alb levels as the disease progressed (both P < 0.05). An improvement of aforementioned phenomena was observed in patients with SAP following treatment, indirectly indicating that serum Claudin-5 level was a positive indicator of vascular leakage. ROC curve analysis showed that serum Claudin-5 levels in patients with AP exhibited the highest accuracy for early prediction of SAP, with the area under the ROC curve (AUC) of 0.948. When serum Claudin-5 levels ≥2 997 ng/L, the sensitivity for early screening for SAP was 100% and the specificity was 88.89%. Multifactorial ridge regression analysis showed that serum Claudin-5 level, PCT and APACHEⅡscore could be used as independent risk factors for early prediction of SAP (all P < 0.05). Conclusion:Serum Claudin-5 levels facilitate early prediction of SAP and are strongly associated with inflammatory response and vascular leakage.