1.Application of Carbon Nanoparticle-Manganese Dioxide Injection in Gastrointestinal Staining-Based Marking and Localization in Rats and Pigs
Wanlin CHEN ; Qingrui DONG ; Mengtao LI ; Nan LIN ; Hu ZHAO ; Zaizhong ZHANG ; Lingjun ZENG ; Pei LI ; Jin YANG ; Yu WANG ; Aiwen HUANG
Laboratory Animal and Comparative Medicine 2026;46(5):727-739
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.
2.Surgical treatment of primary giant gastrointestinal stromal tumor
Zaizhong ZHANG ; Pan ZHAO ; Chunhong XIAO ; Meiping WANG ; Weixuan HONG ; Junwei FANG ; Lie WANG
Journal of Clinical Surgery 2025;33(6):581-584
Objective To explore the surgical treatment experience of primary giant gastrointestinal stromal tumors(GIST)(with isolated lesions with a maximum diameter>10 cm).Methods A retrospective analysis was conducted on the clinical and pathological data of 67 patients with primary giant GIST admitted from January 2018 to December 2024.Among them,35 cases underwent surgical operations after preoperative neoadjuvant therapy(25 effective cases and 10 ineffective cases)(neoadjuvant therapy group).Due to the initial diagnosis assessment expecting radical(R0)resection(13 cases),or preoperative complications(12 cases),or difficulty in obtaining a pathological diagnosis through puncture biopsy(7 cases),32 cases underwent direct surgery without neoadjuvant therapy(direct surgery group).Compare the general information,tumor condition,surgical condition,postoperative recovery,postoperative pathology,postoperative adjuvant therapy,and recurrence between two groups.Results Comparative analysis revealed that there was no statistically significant difference(P>0.05)between the neoadjuvant therapy group and the direct surgery group in terms of gender,age,primary tumor location,initial maximum diameter,growth type,localized or locally advanced stage,and postoperative follow-up time.The maximum diameters of the tumors before surgery in the neoadjuvant therapy group and the direct surgery group were(12.4±7.1)cm and(18.2±5.0)cm respectively,and the operation times were(125.4±30.6)minutes and(153.0±31.7)minutes respectively.The intraoperative blood loss was(228.3±76.4)ml and(300.3±67.2)ml,respectively.The postoperative hospital stay was(9.1±2.6)days and(11.1±3.2)days,respectively.There was a statistically significant difference between the two groups(P<0.05).The proportion of laparoscopic surgery in the neoadjuvant therapy group was 17.1%,which was higher than that in the direct surgery group(0),and the difference was statistically significant(P<0.05).There was no statistically significant difference between the two groups in terms of the proportion of tumor rupture,combined organ resection,postoperative complications and postoperative recurrence(P>0.05).Conclusion Primary giant gastrointestinal stromal tumors can mostly be reduced in size and progression through neoadjuvant therapy,improving the chances of minimally invasive surgery.However,there is also a risk of tumor progression during neoadjuvant therapy leading to increased surgical difficulty or even loss of curative surgical opportunities.
3.Surgical treatment of primary giant gastrointestinal stromal tumor
Zaizhong ZHANG ; Pan ZHAO ; Chunhong XIAO ; Meiping WANG ; Weixuan HONG ; Junwei FANG ; Lie WANG
Journal of Clinical Surgery 2025;33(6):581-584
Objective To explore the surgical treatment experience of primary giant gastrointestinal stromal tumors(GIST)(with isolated lesions with a maximum diameter>10 cm).Methods A retrospective analysis was conducted on the clinical and pathological data of 67 patients with primary giant GIST admitted from January 2018 to December 2024.Among them,35 cases underwent surgical operations after preoperative neoadjuvant therapy(25 effective cases and 10 ineffective cases)(neoadjuvant therapy group).Due to the initial diagnosis assessment expecting radical(R0)resection(13 cases),or preoperative complications(12 cases),or difficulty in obtaining a pathological diagnosis through puncture biopsy(7 cases),32 cases underwent direct surgery without neoadjuvant therapy(direct surgery group).Compare the general information,tumor condition,surgical condition,postoperative recovery,postoperative pathology,postoperative adjuvant therapy,and recurrence between two groups.Results Comparative analysis revealed that there was no statistically significant difference(P>0.05)between the neoadjuvant therapy group and the direct surgery group in terms of gender,age,primary tumor location,initial maximum diameter,growth type,localized or locally advanced stage,and postoperative follow-up time.The maximum diameters of the tumors before surgery in the neoadjuvant therapy group and the direct surgery group were(12.4±7.1)cm and(18.2±5.0)cm respectively,and the operation times were(125.4±30.6)minutes and(153.0±31.7)minutes respectively.The intraoperative blood loss was(228.3±76.4)ml and(300.3±67.2)ml,respectively.The postoperative hospital stay was(9.1±2.6)days and(11.1±3.2)days,respectively.There was a statistically significant difference between the two groups(P<0.05).The proportion of laparoscopic surgery in the neoadjuvant therapy group was 17.1%,which was higher than that in the direct surgery group(0),and the difference was statistically significant(P<0.05).There was no statistically significant difference between the two groups in terms of the proportion of tumor rupture,combined organ resection,postoperative complications and postoperative recurrence(P>0.05).Conclusion Primary giant gastrointestinal stromal tumors can mostly be reduced in size and progression through neoadjuvant therapy,improving the chances of minimally invasive surgery.However,there is also a risk of tumor progression during neoadjuvant therapy leading to increased surgical difficulty or even loss of curative surgical opportunities.
4.Exploration of the clinical application of combined endoscopic and laparoscopic surgery in early gastric cancer: 15 cases
Zhongbiao CHEN ; Dazhou LI ; Zaizhong ZHANG ; Pan ZHAO ; Long YI ; Ruifeng YE ; Qin GAO ; Wen WANG ; Lie WANG
Chinese Journal of Gastrointestinal Surgery 2023;26(8):757-762
Objective:To investigate the application of combined gastroscopy and laparoscopy (dual scope) in the treatment of early gastric cancer.Methods:In this descriptive case series study, we retrospectively collected data on 15 patients with cT1b stage gastric cancer who had undergone combined laparoscopic and endoscopic surgery in the 900th Hospital of the People's Liberation Army of China from May 2020 to October 2022. The study cohort comprised nine men and six women of median age 59 (range: 47–76) years and median body mass index 20.9 (range: 18.3–26.2) kg/m 2. Seven of the lesions were located on the lesser curvature of the gastric antrum and eight in the gastric angle. All lesions were biopsied for pathological examination and evaluated by endoscopic ultrasonography, followed by endoscopic submucosal dissection (ESD) and laparoscopic regional lymph node dissection. Studied variables included surgical and pathological features, postoperative factors, and outcomes. Results:In this group of patients, the median (range) operative time for ESD was 45 (30–82) minutes, the duration of laparoscopic lymph node dissection (45.1±8.6) minutes, and the median (range) intraoperative blood loss during lymph node dissection 30 (10–80) mL. Of the 13 patients with negative postoperative horizontal margins, four were stage SM1 and had no lymph node metastases (Stage SM1) and nine were Stage SM2, of which had one positive regional lymph node and two received additional standard distal gastrectomy with D2 lymphadenectomy concurrently because of positive ESD specimens (lymph node negative). No lymph node metastases were found in the surgical specimens of these patients. The remaining two patients had positive vertical margins; both had undergone concurrent standard distal gastrectomy with D2 lymphadenectomy. One of them was found to be lymph node positive (No. 3, one node). Four patients had impaired gastric emptying after dual-scope treatment, all of whom recovered well with symptomatic management; one patient with a suspected lymphatic leak was also managed conservatively. There were no cases of postoperative bleeding, abdominal infection, or incisional infection. At a median follow-up of 14 (6–26) months, no tumor recurrence or metastasis had been identified in any of the patients. Three patients had a grade B nutrition score 3 to 6 months after surgery, all of whom had undergone major gastrectomy, and two patients who had undergone dual-scope surgery reported an increase in acid reflux and belching after surgery compared with the preoperative period.Conclusion:A combined technique is safe and feasible for the treatment of early gastric cancer and is worthy of further exploration.
5.Progress in the treatment of early gastric cancer with Laparoscopic and endoscopic cooperative surgery
Chen LIN ; Zaizhong ZHANG ; Lie WANG
Chinese Journal of Gastrointestinal Surgery 2023;26(8):798-802
With the introduction of minimally invasive methods into the field of surgery, the concept of early gastric cancer (EGC) treating has gradually changed from the pursuit of standardized traditional surgical methods to precise, individualized, interdisciplinary collaborative management. Both endoscopic therapy and laparoscopic surgery have their limitations for early gastric cancer treatment. Meanwhile, Laparoscopic and endoscopic cooperative surgery (LECS) combines the advantages of endoscopy and laparoscopy to perform local gastric resection and regional lymph node dissection, providing a more effective surgical approach for radical resection of early gastric cancer. The application of LECS in the treatment of early gastric cancer has been increasing, from the initial laparoscopy-assisted endoscopic full-thickness resection to the evolvement of a variety of improved procedures such as combined laparoscopic and endoscopic approach for neoplasia with a non-exposure technique, non-exposed endoscopic wall-inversion surgery, and the possibility of combined (sentinel lymph node drainage area) regional lymph node dissection or sentinel lymph node navigation surgery, which expands the indications for endoscopic surgery and maximizes the preservation of normal gastric tissue structure and function while ensuring radical treatment, and will certainly become an important development direction in the treatment of early gastric cancer in the future.
6.Exploration of the clinical application of combined endoscopic and laparoscopic surgery in early gastric cancer: 15 cases
Zhongbiao CHEN ; Dazhou LI ; Zaizhong ZHANG ; Pan ZHAO ; Long YI ; Ruifeng YE ; Qin GAO ; Wen WANG ; Lie WANG
Chinese Journal of Gastrointestinal Surgery 2023;26(8):757-762
Objective:To investigate the application of combined gastroscopy and laparoscopy (dual scope) in the treatment of early gastric cancer.Methods:In this descriptive case series study, we retrospectively collected data on 15 patients with cT1b stage gastric cancer who had undergone combined laparoscopic and endoscopic surgery in the 900th Hospital of the People's Liberation Army of China from May 2020 to October 2022. The study cohort comprised nine men and six women of median age 59 (range: 47–76) years and median body mass index 20.9 (range: 18.3–26.2) kg/m 2. Seven of the lesions were located on the lesser curvature of the gastric antrum and eight in the gastric angle. All lesions were biopsied for pathological examination and evaluated by endoscopic ultrasonography, followed by endoscopic submucosal dissection (ESD) and laparoscopic regional lymph node dissection. Studied variables included surgical and pathological features, postoperative factors, and outcomes. Results:In this group of patients, the median (range) operative time for ESD was 45 (30–82) minutes, the duration of laparoscopic lymph node dissection (45.1±8.6) minutes, and the median (range) intraoperative blood loss during lymph node dissection 30 (10–80) mL. Of the 13 patients with negative postoperative horizontal margins, four were stage SM1 and had no lymph node metastases (Stage SM1) and nine were Stage SM2, of which had one positive regional lymph node and two received additional standard distal gastrectomy with D2 lymphadenectomy concurrently because of positive ESD specimens (lymph node negative). No lymph node metastases were found in the surgical specimens of these patients. The remaining two patients had positive vertical margins; both had undergone concurrent standard distal gastrectomy with D2 lymphadenectomy. One of them was found to be lymph node positive (No. 3, one node). Four patients had impaired gastric emptying after dual-scope treatment, all of whom recovered well with symptomatic management; one patient with a suspected lymphatic leak was also managed conservatively. There were no cases of postoperative bleeding, abdominal infection, or incisional infection. At a median follow-up of 14 (6–26) months, no tumor recurrence or metastasis had been identified in any of the patients. Three patients had a grade B nutrition score 3 to 6 months after surgery, all of whom had undergone major gastrectomy, and two patients who had undergone dual-scope surgery reported an increase in acid reflux and belching after surgery compared with the preoperative period.Conclusion:A combined technique is safe and feasible for the treatment of early gastric cancer and is worthy of further exploration.
7.Progress in the treatment of early gastric cancer with Laparoscopic and endoscopic cooperative surgery
Chen LIN ; Zaizhong ZHANG ; Lie WANG
Chinese Journal of Gastrointestinal Surgery 2023;26(8):798-802
With the introduction of minimally invasive methods into the field of surgery, the concept of early gastric cancer (EGC) treating has gradually changed from the pursuit of standardized traditional surgical methods to precise, individualized, interdisciplinary collaborative management. Both endoscopic therapy and laparoscopic surgery have their limitations for early gastric cancer treatment. Meanwhile, Laparoscopic and endoscopic cooperative surgery (LECS) combines the advantages of endoscopy and laparoscopy to perform local gastric resection and regional lymph node dissection, providing a more effective surgical approach for radical resection of early gastric cancer. The application of LECS in the treatment of early gastric cancer has been increasing, from the initial laparoscopy-assisted endoscopic full-thickness resection to the evolvement of a variety of improved procedures such as combined laparoscopic and endoscopic approach for neoplasia with a non-exposure technique, non-exposed endoscopic wall-inversion surgery, and the possibility of combined (sentinel lymph node drainage area) regional lymph node dissection or sentinel lymph node navigation surgery, which expands the indications for endoscopic surgery and maximizes the preservation of normal gastric tissue structure and function while ensuring radical treatment, and will certainly become an important development direction in the treatment of early gastric cancer in the future.
8.Update on Diagnosis and Treatment of Gastrointestinal Stromal Tumors
Chen LIN ; Zaizhong ZHANG ; Lie WANG
Cancer Research on Prevention and Treatment 2022;49(1):1-4
In recent years, with the emergence of new research evidence, the domestic and foreign guidelines in the field of gastrointestinal stromal tumors (GISTs) have been updated. The adjusted contents cover almost every link of GISTs management, from GISTs diagnosis, biological behavior, surgical treatment to targeted drug treatment. Since 2020, the NCCN of the United States has separated the contents related to GISTs from the clinical practice guide for soft tissue sarcoma for the first time to form 2021 V.1 versions. The CSCO has also adjusted and upgraded the previous consensus of Chinese experts on the diagnosis and treatment of GISTs to 2020 and 2021 versions of the guidelines for the diagnosis and treatment of GISTs. This opens a new model of accurate diagnosis and treatment of GISTs under the guidance of evidence-based medicine. The listing of new targeted drugs afatinib and ripretinib is expected to get rid of the drug-resistant treatment dilemma of metastatic GISTs, enrich the back-line treatment camp, provide more opportunities for surgical intervention, and then bring survival benefits to patients with advanced GISTs.
9. Nutritional support therapy during treatment of chronic critical illness
Chunhong XIAO ; Zaizhong ZHANG ; Jingxiang SONG ; Lie WANG
Chinese Journal of Gastrointestinal Surgery 2019;22(11):1016-1020
Chronic critical illness (CCI) refers to a group of critically ill patients who survive the acute phase of intensive care, but with persistent organ dysfunction, thus entering a chronic period of continuous dependence on life support system, and still need to stay in intensive care unit (ICU) for a long time. Persistent inflammatory response-immunosuppression-catabolic syndrome (PICS) is the main pathophysiological feature of CCI. Three factors interact to form a vicious circle, leading to poor prognosis. Nutritional support therapy is a key link in the comprehensive treatment of CCI. Enteral nutrition (EN) should be started as soon as possible if conditions permit. If EN can not be implemented, temporary or transitional parenteral nutrition (PN) should be used, and EN should be added gradually in time. At the same time, the amount of PN should be gradually reduced. When EN meets more than 60% of patients’ energy and protein requirements, PN can be considered to be discontinued. The main strategies and functions of CCI nutritional support therapy are as follows: strengthening high protein supply to correct negative nitrogen balance and inhibit catabolism, selecting branched chain amino acids (BCAA) to promote anabolism, using immunomodulators (arginine, ω3 polyunsaturated fatty acids) to improve immune suppression and inflammatory response, supplementing micronutrients (vitamins and trace elements) to counteract the decrease in intake and the increase in consumption, and adding probiotics to maintain the intestinal microecological balance, and so on. Reasonable nutritional support therapy not only improve malnutrition of CCI patients, but also help to reduce complications, thus speeding up rehabilitation, improving prognosis, shortening ICU hospitalization time, and even reducing mortality.
10. Application of preoperative endoscopic ultrasonography localization in adenocarcinoma of the esophagogastric junction
Yongwei XIE ; Shunkai ZHOU ; Xuegang FENG ; Baoquan LIN ; Yongpeng HUANG ; Zaizhong ZHANG ; Yu WANG ; Shengsheng YANG
Chinese Journal of Thoracic and Cardiovascular Surgery 2019;35(10):612-616
Objective:
Preliminary study on the clinical effect of preoperative ultrasound endoscopy combined with staining labeling technique to locate the actual boundary of esophageal and gastric cancer
Methods:
From September 1, 2015 to October 30, 2017, 18 patients with esophageal adenocarcinoma were enrolled in this study. The actual boundaries of esophageal and gastric-derived adenocarcinoma lesions were localized by endoscopic ultrasonography and staining. There were 10 males and 8 females. After completing the preoperative examination, 1-2 days before operation, endoscopic ultrasonography was used to locate the edge of the lesion. Two point injection of carbon nano suspension was used to mark the location of 1cm at the longest distance from the longitudinal axis of the tumor. According to the length of longitudinal axial staining, the thoracotomy was performed. Intraoperative proximal margin resection was used to send frozen pathology. According to the results of freezing, the operation was decided. After the operation, the specimens from the margin of the tumor were segmented into paraffin section, which was about 0.5cm in each segment, and the tumor cells were observed under the electron microscope at all levels of the paraffin sections.
Results:
The average time of preoperative endoscopic ultrasonography staining was(10.16±1.38) min, and the diameter of nano carbon diffusion was(1.43±0.41)cm. All patients in the operation could clearly see the nano carbon staining area under the naked eye. In the field, the average time of locating lesions was(1.27±0.53)min. 5 patients underwent thoracoabdominal surgery and 13 underwent abdominal surgery. The average length of the cut margin of the tumor was(4.74±1.12)cm, and the frozen pathology of the incision margin was negative, and no additional operation was performed. The routine pathology confirmed that all the specimens were negative.
Conclusion
The staining and labeling technique for adenocarcinoma of the esophagogastric junction under endoscopic ultrasonography can detect the tumor edge and the scope of invasion accurately. It provides guidance and guarantee for the smooth implementation of AEG precision surgery. It is a safe, rapid and effective positioning technique.

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