1.Decoding the immune microenvironment of secondary chronic myelomonocytic leukemia due to diffuse large B-cell lymphoma with CD19 CAR-T failure by single-cell RNA-sequencing.
Xudong LI ; Hong HUANG ; Fang WANG ; Mengjia LI ; Binglei ZHANG ; Jianxiang SHI ; Yuke LIU ; Mengya GAO ; Mingxia SUN ; Haixia CAO ; Danfeng ZHANG ; Na SHEN ; Weijie CAO ; Zhilei BIAN ; Haizhou XING ; Wei LI ; Linping XU ; Shiyu ZUO ; Yongping SONG
Chinese Medical Journal 2025;138(15):1866-1881
BACKGROUND:
Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T (CAR-T) cell therapy, underscoring the need for a detailed investigation. Given the limited variety of secondary tumor types reported to date, a comprehensive characterization of the various secondary tumors arising after CAR-T therapy is essential to understand the associated risks and to define the role of the immune microenvironment in malignant transformation. This study aims to characterize the immune microenvironment of a newly identified secondary tumor post-CAR-T therapy, to clarify its pathogenesis and potential therapeutic targets.
METHODS:
In this study, the bone marrow (BM) samples were collected by aspiration from the primary and secondary tumors before and after CD19 CAR-T treatment. The CD45 + BM cells were enriched with human CD45 microbeads. The CD45 + cells were then sent for 10× genomics single-cell RNA sequencing (scRNA-seq) to identify cell populations. The Cell Ranger pipeline and CellChat were used for detailed analysis.
RESULTS:
In this study, a rare type of secondary chronic myelomonocytic leukemia (CMML) were reported in a patient with diffuse large B-cell lymphoma (DLBCL) who had previously received CD19 CAR-T therapy. The scRNA-seq analysis revealed increased inflammatory cytokines, chemokines, and an immunosuppressive state of monocytes/macrophages, which may impair cytotoxic activity in both T and natural killer (NK) cells in secondary CMML before treatment. In contrast, their cytotoxicity was restored in secondary CMML after treatment.
CONCLUSIONS
This finding delineates a previously unrecognized type of secondary tumor, CMML, after CAR-T therapy and provide a framework for defining the immune microenvironment of secondary tumor occurrence after CAR-T therapy. In addition, the results provide a rationale for targeting macrophages to improve treatment strategies for CMML treatment.
Humans
;
Lymphoma, Large B-Cell, Diffuse/therapy*
;
Tumor Microenvironment/genetics*
;
Antigens, CD19/metabolism*
;
Leukemia, Myelomonocytic, Chronic/genetics*
;
Immunotherapy, Adoptive/adverse effects*
;
Male
;
Single-Cell Analysis/methods*
;
Female
;
Sequence Analysis, RNA/methods*
;
Receptors, Chimeric Antigen
;
Middle Aged
2.Effect of Tongfeng Decoction (痛风汤) on NLRP3 Inflammatory Vesicles and Neutrophil Extracellular Traps in Synovial Tissues of Ankle Joints in Acute Gouty Arthritis Model Rats
Yongzheng DENG ; Qingliang MENG ; Junfu MA ; Jiakang CUI ; Kai LI ; Gengfeng WANG ; Chenyang SONG ; Hua BIAN
Journal of Traditional Chinese Medicine 2024;65(17):1816-1824
ObjectiveTo explore the possible mechanism of Tongfeng Decoction (痛风汤) for preventing and treating acute gouty arthritis. MethodsSixty Wistar male rats were divided into normal group, model group, colchicine group and low-, medium- and high-dose Tongfeng Decoction groups according to the random number table, 10 rats in each group. Tongfeng Decoction of 11.34, 22.68 and 45.36 g/kg were given by gavage to low-, medium- and high-dose Tongfeng Decoction groups, colchicine 3.15×10-4 g/(kg·d) to the colchicine group, and normal saline 10 ml/(kg·d) to the normal group and model group respectively for 7 consecutive days. After 1 hour of gavage on day 5, rats in all groups except the normal group were modelled as acute gouty arthritis in the ankle joint of the right hind limb with the modified Coderre's method; rats in the normal group were injected with 0.2 ml of normal saline at the same location. The swelling degree of the ankle joint was measured before modelling and after 6 h, 12 h, 24 h and 48 h of modelling, respectively. HE staining was used to observe the histopathological and morphological changes in the synovial tissue of the ankle joint; immunoblotting and RT-qPCR were used to detect NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), cysteine aspartate protease 1 (Caspase-1), and interleukin 1β (IL-1β) protein and mRNA expression levels in ankle synovial tissues, respectively; immunohistochemistry was used to detect the positive expression of Caspase-1 and IL-1β in ankle synovial tissues; ELISA was used to detect the tumour necrosis factor alpha (TNF-α), IL-1β, and interleukin in serum; immunofluorescence staining was used to observe the formation of neutrophil extracellular traps (NETs) in the synovial tissues of the ankle joints. ResultsCompared with the normal group, rats in the model group showed elevated joint swelling at all time points, significantly increased inflammatory cell infiltration and the number of synovial cell layers in the synovial tissues of the ankle joints, elevated NLRP3, Caspase-1, ASC and IL-1β protein and mRNA expression, elevated positive expression of Caspase-1 and IL-1β, increased formation of NETs, and elevation of TNF-α, IL-6, and IL-1β in serum (P<0.05). Compared with the model group, there was an improvement in synovial cell proliferation and inflammatory cell infiltration of the ankle joint in the colchicine group, high- and medium-dose Tongfeng Decoction groups. In the colchicine group and the high-, medium- and low-dose Tongfeng Decoction groups, the degree of joint swelling, positive expression of Caspase-1, IL-1β and formation of NETs in the synovial tissue of the ankle joint, and TNF-α, IL-6 and IL-1β in serum reduced 24 h and 48 h after modelling; in colchicine group and high-dose Tongfeng Decoction group, NLRP3, ASC, Caspase-1, IL-1β protein and mRNA expression in the synovial tissues of ankle joints all reduced (P<0.05). The colchicine group and high-dose Tongfeng Decoction group were superior to the low-dose Tongfeng Decoction group in reducing ASC, Caspase-1, IL-1β protein and mRNA expression in the ankle synovial tissues, the positive expression of Caspase-1, as well as TNF-α, IL-6, and IL-1β level in serum (P<0.05). ConclusionTongfeng Decoction showed effectiveness for the prevention and treatment of acute gouty arthritis, and its mechanism may be related to the inhibition of the assembly and activation of NLRP3 inflammatory vesicles in ankle synovial tissues, the inhibition of the release of inflammatory factors, and the formation of NETs.
3.Effect of sevoflurane on Ca 2+ transporter expression in cardiomyocytes during right ventricular remodeling in rats with pulmonary arterial hypertension
Wenqian ZHAI ; Yanfei BIAN ; Yuezi SONG ; Yunfei LI ; Hong XU ; Zhigang GUO ; Jiange HAN
Chinese Journal of Anesthesiology 2024;44(3):313-317
Objective:To evaluate the effect of sevoflurane on Ca 2+ transporter expression in cardiomyocytes during right ventricular remodeling in rats with pulmonary arterial hypertension. Methods:Twenty-four clean-grade healthy male Sprague-Dawley rats, aged 8-10 weeks, weighing 200-250 g, were divided into 4 groups ( n=6 each) by the random number table method: control group (CM group), sevoflurane group (CS group), monocrotaline group (M group) and sevoflurane + monocrotaline group (S group). Monocrotaline 60 mg/kg was intraperitoneally injected in group M and group S, and monocrotaline lysate was intraperitoneally injected in group CM. The rats in S and CS groups inhaled 2.5% sevoflurane for 1 h, twice a week, at an interval of 3 days starting from the first day after injection of monocrotaline. Pulmonary artery acceleration time and pulmonary artery ejection time were measured by transthoracic echocardiography at 6 weeks after monocrotaline injection. The chest was exposed under 3% sevoflurane anesthesia, the heart was perfused, and the pulmonary artery branch and right ventricular myocardial tissues were retained. The wall thickness of pulmonary arterioles and cross-section area of right ventricular cardiomyocytes were observed by HE staining. The expression of Ca 2+ transporter in right ventricular cardiomyocytes was detected by Western blot. Results:Compared with CM group, the ratio of pulmonary artery acceleration time to pulmonary artery ejection time was significantly decreased, the cross-section area of right ventricular cardiomyocytes was increased, the wall thickness of pulmonary arteriole was increased, the expression of type 1 sodium-calcium exchange and inositol triphosphate receptor was up-regulated, and the expression of voltage-dependent L-type calcium channel α1C subunit, type 2 ryanodine receptor, sarcoplasmic reticulum calcium pump 2α and proteinphilin-2 was down-regulated in M group ( P<0.01). Compared with group M, the ratio of pulmonary artery acceleration time to pulmonary artery ejection time was significantly increased, the cross-section area of right ventricular cardiomyocytes was decreased, the wall thickness of pulmonary arteriole was decreased, the expression of type 1 sodium-calcium exchange and inositol triphosphate receptor was down-regulated, and the expression of voltage-dependent L-type calcium channel α1C subunit, type 2 ryanodine receptor, sarcoplasmic reticulum calcium pump 2α and proteinphilin-2 was up-regulated in group S ( P<0.01). Conclusions:The mechanism by which sevoflurane improves right ventricular remodeling is related to regulating the expression of Ca 2+ transporter in cardiomyocytes of rats with pulmonary arterial hypertension.
4.Study on epidemiological prevalence and serological marker characteristics of hepatitis E infection
Chengrong BIAN ; Xin LIU ; Ruirui HAN ; Lili ZHAO ; Yeli HE ; Lihua YANG ; Weiwei LI ; Lijuan SONG ; Yingwei SONG ; Yongli LI ; Aixia LIU ; Jinli LOU ; Bo′an LI
Chinese Journal of Laboratory Medicine 2024;47(3):245-251
Objective:This study aims to explore the prevalence of hepatitis E virus (HEV) infection in patients and the screening value of serological indicators for HEV infection patients.Methods:Retrospective analysis was conducted on 97 440 cases of anti-HEV IgM and IgG simultaneously tested in two Beijing hospitals from January 1, 2018 to August 31, 2023. Among them, there were 61 005 males and 36 435 females, with an average age of 51.65±13.05 years old. According to the positivity of anti HEV specific antibodies, they were divided into anti-HEV IgM positive group (3 588 cases), anti-HEV IgG positive group (18 083 cases), and anti-HEV antibody negative group (78 892 cases). Results of HEV RNA, liver function, AFP, PIVKA-Ⅱ and PT were collected, and their basic clinical information were recorded. The prevalence of HEV infection in patients, as well as the relationship between the positivity of anti-HEV specific antibodies and the patient′s age group, HEV RNA, and clinical characteristics were analyzed.Results:Among 97 440 patients who tested anti-HEV IgM and IgG simultaneously, the positivity rate of anti-HEV IgM was 3.68% (3 588/97 440), and was 18.56% for anti-HEV IgG (18 083/97 440). The overall positivity rates of anti-HEV IgM in two Beijing hospitals from 2018 to 2023 were 2.51%, 2.53%, 3.02%, 4.59%, 5.72%, and 4.26% ( χ2=1 401.73, P<0.001), while the positivity rates of anti-HEV IgG were 12.56%, 12.32%, 12.85%, 22.65%, 27.42%, and 26.66% ( χ2=1 058.29, P<0.001). These rates showed a gradual increase until 2023 when a decline was observed. The positivity rates of anti-HEV IgM (2.28%, 3.60%, 4.47%) ( χ2=89.62, P<0.001) and IgG (4.71%, 17.86%, 25.94%) ( χ2=2 017.32, P<0.001) increased with age in patients who aged 1-30, >30-60, and over 60 years old. The age and ALB values of patients in the anti-HEV IgM positive group were lower than the IgG-positive group, while the proportion of males, TBIL, ALT, AFP and PT values were higher than the IgG-positive group, and the differences were statistically significance ( P<0.05). Furthermore, patients in both the anti-HEV IgM and IgG positive groups had higher age, male proportion, TBIL, ALT, AFP, PIVKA-Ⅱ, and PT values than the anti-HEV negative group. Additionally, both groups had lower ALB values than the anti-HEV negative group, all of which were statistically significant ( P<0.05). 2 162 HEV infected patients were grouped based on HEV RNA positivity. The proportion of anti-HEV IgM single positive, IgG single positive, IgM+IgG double positive, and antibody negative patients in the HEV RNA positive group were 5.42% (18/332), 3.62% (12/332), 90.36% (300/332), and 0.60% (2/332), respectively. Among them, the proportion of anti-HEV IgM+IgG double positive patients in the HEV RNA positive group was higher than that in the HEV RNA negative group ( χ2=302.87, P<0.001), while the proportion of anti-HEV IgG single positive ( χ2=174.36, P<0.001) and anti-HEV antibody negative patients ( χ2=59.28, P<0.001) were lower than that in the HEV RNA negative group, both of which were statistically significant ( P<0.001). In addition, the positive rates of HEV RNA in anti-HEV IgM positive, IgG positive, and antibody negative patients were 29.23% (318/1 088), 17.59% (312/1 774), and 0.65% (2/306), respectively. Conclusion:The HEV infection rate among patients declined in 2023. HEV infection is age-related, with older individuals being more susceptible. Abnormal liver function and jaundice were commonly observed during HEV infection. It is crucial to note that the absence of anti-HEV specific antibodies cannot rule out HEV infection; therefore, additional testing for HEV RNA and/or HEV Ag is necessary for accurate diagnosis.
5.Honey-processed Hedysari Radix in treatment of spleen-Qi deficiency rats based on metabonomics of the cecum contents
Yu-Jing SUN ; Qin-Jie SONG ; Yan-Jun WANG ; Tian-Tian BIAN ; Yu-Gui ZHANG ; Xian-Wei LI ; Guo-Feng LI ; Yue-Feng LI
The Chinese Journal of Clinical Pharmacology 2024;40(4):584-588
Objective To find potential biomarkers and analyzing metabolic pathways of the treatment by honey-processed Hedysari Radix,the cecal contents of rats with spleen-Qi deficiency were used as samples for analysis.Methods Sixty male SD rats were randomly divided into blank,model,experimental and control groups.The rats in other groups except the control group were carried out by using the three-factor compound modeling method of bitter-cold diarrhea,excessive exertion and hunger and satiety disorders.Experimental group was given 12.60 g·kg-1 honey-processed Hedysari Radix;control group was given 0.63 g·kg-1 lactobacillus bifidum triplex tabletsa;control and model groups received with equal volume of distilled water for a total of 15 days.Measure body weight,anal temperature,immune organ index of rats.Ultra-pressure liquid chromatography-quadrupole-exactive-mass spectrometry technology was used to measure the levels of endogenous metabolites in cecum contents.Orthogonal partial least squares discriminant analysis and database"Kyoto Encyclopedia of Genes and Genomes"were used to identify potential differential metabolites and possible metabolic pathways.Results After the intervention,the average body weight of the experimental,control,model and blank groups was(216.87±7.85),(210.96±9.03),(159.47±5.18)and(293.51±22.98)g;anal temperature was(36.14±0.48),(35.40±0.64),(34.50±0.78)and(36.61±0.34)℃;the thymus indexes were(1.19±0.20),(1.24±0.25),(0.47±0.15)and(1.31±0.21)mg·g-1;the spleen indexes were(1.95±0.33),(2.18±0.28),(1.61±0.27)and(2.29±0.24)mg·g-1.Compared with the model group,the above indexes of the experimental group and the control group were significantly increased(all P<0.01).A total of 14 potential biomarkers of Honey-processed Hedysari Radix in treating spleen-Qi deficiency syndrome were screened out in this study,which mainly involved amino acid metabolism such as tryptophan and glutamate,riboflavin metabolism and adenosine 5'-monophosphate-activated protein kinase metabolism.Conclusion Honey-processed Hedysari Radix can further protect the intestinal mucosal barrier and reduce the intestinal inflammatory response by improving the metabolic level of cecum contents in rats with spleen-Qi deficiency in cecum contents,thus exerting the effect of strengthening the spleen and tonifying the Qi.
6.Carnosine attenuates OGD/R damage to BV2 cells by inhibiting ROS/NLRP3/GSDMD-mediated pyroptosis
Rui-Li RAN ; Yu-Tong WANG ; Jun-Qiu SONG ; Jiang BIAN ; De-Wei WANG ; Xiao-Han JIANG ; Fu-Lin YOU ; Jing YANG
Chinese Pharmacological Bulletin 2024;40(11):2150-2158
Aim To investigate the protective effect of carnosine on BV2 cell damage induced by oxygen-glu-cose deprivation/reperfusion(OGD/R)and its role in mediating pyrodeath through the ROS/NLRP3/GSDMD pathway.Methods BV2 cells were randomly divided into the control group(Con),model group(OGD/R),carnosine group(OGD/R+CAR),inhibitor group(OGD/R+MCC950),and carnosine+inhibitor group(OGD/R+CAR+MCC950).The cell survival rate was detected by MTT assay.The release rate of lactate dehydrogenase(LDH)in cell supernatant was detected by microenzyme labeling method.Cell damage was as-sessed using Hoechst 33342/SYTOX Green staining.ROS levels in cells were detected by DCFH-DA.The nucleation level of NF-κB p65 was observed by immu-nofluorescence.The protein expression levels of NLRP3,ASC,cleaved caspase-1,and GSDMD-N were detected by Western blot.The levels of IL-1 β and IL-18 in the supernatant were detected by ELISA.Results Com-pared with Con group,the survival rate of cells in the OGD/R group was significantly reduced,LDH release was significantly raised,cell morphology was damaged,and the positive rate of SYTOX Green was significantly elevated with ROS level in cells.The fluorescence in-tensity of NF-κB p65 in the nucleus increased,and the protein expression levels of NLRP3,ASC,cleaved caspase-1,GSDMD-N increased significantly,and the levels of IL-1 β and IL-18 in the cell superserum in-creased significantly.Compared with the OGD/R group,the survival rate of cells in other groups in-creased significantly,the LDH release rate significantly decreased,and the cell damage was improved to a cer-tain extent.The positive rate of SYTOX Green and ROS production in cells significantly decreased,and the fluorescence intensity of NF-κB p65 in nucleus markedly decreased.The expression levels of related proteins and the levels of IL-1 β and IL-18 in cell super-natant significantly decreased.Conclusion Carnosine can protect BV2 cells from OGD/R-induced damage by inhibiting oxidative stress and NF-κB activation,then inhibiting NLRP3/GSDMD signaling pathway.
7.Anti-Helicobacter pylori Mechanism of Chinese Medicine: A Review
Huiying WAN ; Chao LI ; Wei LI ; Xinbo SONG ; Lijuan ZHANG ; Yuhong BIAN
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(3):203-212
Helicobacter pylori (Hp), a spiral-shaped microaerophilic Gram-negative bacterium that has been classified as a class Ⅰ carcinogen by the World Health Organization, is associated with a variety of digestive system diseases. With the popularization of antibiotic therapy, Hp resistance has become the main reason for the failure of the eradication treatment of Hp. A variety of Chinese medicines have been proved to have anti-Hp effects, which are expected to serve as new options for the eradication of Hp. By reviewing the recent literature in China and abroad, we summarized the understanding of Chinese medicines in the treatment of Hp infection and elaborated on the mechanisms from two aspects: direct killing and indirect inhibition. On the one hand, Chinese medicines can directly kill Hp by inhibiting the growth, respiration, and metabolism of Hp, destroying the morphological structure of Hp, and inhibiting the formation of Hp biofilm. On the other hand, Chinese medicines can inhibit Hp by reducing Hp adhesion and colonization, regulating Hp-caused immune response, inhibiting Hp-caused inflammation, and alleviating the Hp-caused oxidative stress and gastric mucosal injury. Specifically, the indirect inhibition of Hp can be achieved via the following ways. Chinese medicines can reduce Hp adhesion and colonization by reducing Hp motility, inhibiting urease activity and the expression of related genes, and decreasing the production of adhesion proteins. They can regulate the Hp-caused immune responses by enhancing the immune protective response, modulating lysosomal function and immune cytokines, avoiding the immune evasion of Hp, and maintaining the balance between immunity and inflammation. Chinese medicines can inhibit Hp-caused inflammatory responses by inhibiting the release of inflammatory cytokines, down-regulating the expression of virulence factors, and regulating the targets and signaling pathways in the treatment of inflammation. In addition, Chinese medicines can alleviate the Hp-caused oxidative stress and gastric mucosal injury by improving the activities of antioxidant enzymes and oxidases, regulating the generation of reactive oxygen species and reactive nitrogen, and inhibiting inflammatory mediators. This article systematically introduces the mechanisms of Chinese medicines against Hp, aiming to provide a theoretical and scientific basis for the research and clinical application of Chinese medicines against Hp.
8.Safety of the strategy of minimizing intestinal resection during surgery for pelvic radiation- induced terminal small intestinal stenosis
Kai WANG ; Xiaodong NI ; Bangjian BIAN ; Xuan ZHANG ; Haixiao FU ; Tengteng LI ; Hao LIU ; Wei FU ; Jun SONG ; Jian WANG
Chinese Journal of Gastrointestinal Surgery 2023;26(10):947-954
Objective:To investigate the efficacy of strategies for minimizing small bowel resection during surgery for pelvic radiation-induced terminal small intestinal stenosis in preventing postoperative complications such as anastomotic leakage and short bowel syndrome.Methods:This was a retrospective cohort study. There are two subtypes of chronic radiation enteritis (CRE) with combined intestinal stenosis and intestinal obstruction: (1) Type I: terminal ileal lesions with a normal ileal segment of 2–20 cm between the ileal lesion and ileocecal junction; and (2) Type II: the lesion is located in the small bowel at a distance from the ileocecal region, usually accompanied by extensive damage to the bowel segments outside the lesion. The indications for minimal bowel resection are as follows: (1) diagnosis of Type I small bowel CRE; (2) absence of radiological evidence of rectosigmoid damage; and (3) absence of colonic obstruction. The contraindications are: (1) stenotic, penetrating lesions of the distal cecum; (2) emergency surgery; (3) recurrence of malignant tumor or history of radiotherapy for recurrent malignant tumor; (4) interval between radiotherapy and surgery <6 months; and (5) history of preoperative small bowel resection or abdominal chemotherapy. Case data of 40 patients with Type I CRE who met the above criteria and had undergone minimal bowel resection between April 2017 and December 2019 were retrospectively analyzed (minimal bowel resection group; including 13 patients from Jinling Hospital, 16 from the Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, and 11 from the Affiliated Hospital of Xuzhou Medical University). Forty patients with Type I CRE who had undergone resection of intestinal stenosis lesions and the ileocecal region between October 2015 and March 2017 were included as historical controls (conventional resection group; all from Jinling Hospital). The specific strategy for minimal bowel resection was one-stage partial ileal resection+ileo anastomosis+protective small bowel stoma. In contrast, conventional resection comprised ileocecal resection+ileocecal-ascending colon anastomosis. Postoperative complications, intraoperative and postoperative recovery, and changes in postoperative quality of life were analyzed in both groups. The severity of postoperative complications was assessed by Clavien-Dindo and the Comprehensive Complication Index (CCI). Karnofsky performance scores (KPS) were used to evaluate the quality of life of patients in the two groups preoperatively and postoperatively. The higher the KPS score, the better the quality of life.Results:Baseline patient characteristics did not differ significantly between the two groups ( P>0.05). Compared with the conventional resection group, the length of small bowel resected in the minimal bowel resection group (51 [20–200] cm vs. 91 [60–200] cm, Z=5.653, P<0.001), duration of postoperative total enteral nutrition [9 (3–18) days vs. 12 (4–50) days, Z=2.172, P=0.030], and duration of postoperative hospital stay [17 (9–24) days vs 29 (13–57) days, Z=6.424, P<0.001] were shorter; all of these differences are statistically significant. The overall incidence of postoperative complications was lower in the minimal bowel resection group than in the conventional resection group [20.0% (8/40) vs. 70.0% (28/40), χ 2=19.967, P<0.001], These comprised short bowel syndrome [5.0% (2/40) vs. 25.0% (10/40), χ 2=6.274, P=0.012], anastomotic leakage or fistula [2.5% (1/40) vs. 22.5% (9/40), χ 2=7.314, P=0.014], and pleural effusion [7.5% (3/40) vs. 25.0% (10/40), χ 2=4.500, P=0.034], all of which occurred less often in the minimal bowel resection than conventional resection group. The CCI index was also lower in the minimal bowel resection group than in the conventional resection group [CCI>40: 2.5% (1/40) vs. 12.5% (5/40), Z=18.451, P<0.001]. KPS scores were higher in the minimal bowel resection group 1 and 3 months postoperatively than they had been 1 day preoperatively (79.9±4.7 vs. 75.3±4.1, 86.2±4.8 vs. 75.3±4.1, both P<0.05). In the minimal bowel resection group, seven patients were satisfied with their current quality of life and refused to undergo stoma reduction at follow-up and one deferred stoma reduction because of rectal bleeding. The remaining 32 patients underwent stoma reduction 3 to 12 months after surgery, 26 of whom underwent ileo-cecal anastomosis. The remaining six underwent resection of the stoma and anastomosis of the ileum to the ascending colon. Conclusions:The strategy of minimal small bowel resection in patients with radiation-induced bowel injuries reduces the length of resected small bowel, decreases the risk and severity of postoperative complications, and is associated with a better prognosis and quality of life than conventional resection.
9.Safety of the strategy of minimizing intestinal resection during surgery for pelvic radiation- induced terminal small intestinal stenosis
Kai WANG ; Xiaodong NI ; Bangjian BIAN ; Xuan ZHANG ; Haixiao FU ; Tengteng LI ; Hao LIU ; Wei FU ; Jun SONG ; Jian WANG
Chinese Journal of Gastrointestinal Surgery 2023;26(10):947-954
Objective:To investigate the efficacy of strategies for minimizing small bowel resection during surgery for pelvic radiation-induced terminal small intestinal stenosis in preventing postoperative complications such as anastomotic leakage and short bowel syndrome.Methods:This was a retrospective cohort study. There are two subtypes of chronic radiation enteritis (CRE) with combined intestinal stenosis and intestinal obstruction: (1) Type I: terminal ileal lesions with a normal ileal segment of 2–20 cm between the ileal lesion and ileocecal junction; and (2) Type II: the lesion is located in the small bowel at a distance from the ileocecal region, usually accompanied by extensive damage to the bowel segments outside the lesion. The indications for minimal bowel resection are as follows: (1) diagnosis of Type I small bowel CRE; (2) absence of radiological evidence of rectosigmoid damage; and (3) absence of colonic obstruction. The contraindications are: (1) stenotic, penetrating lesions of the distal cecum; (2) emergency surgery; (3) recurrence of malignant tumor or history of radiotherapy for recurrent malignant tumor; (4) interval between radiotherapy and surgery <6 months; and (5) history of preoperative small bowel resection or abdominal chemotherapy. Case data of 40 patients with Type I CRE who met the above criteria and had undergone minimal bowel resection between April 2017 and December 2019 were retrospectively analyzed (minimal bowel resection group; including 13 patients from Jinling Hospital, 16 from the Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, and 11 from the Affiliated Hospital of Xuzhou Medical University). Forty patients with Type I CRE who had undergone resection of intestinal stenosis lesions and the ileocecal region between October 2015 and March 2017 were included as historical controls (conventional resection group; all from Jinling Hospital). The specific strategy for minimal bowel resection was one-stage partial ileal resection+ileo anastomosis+protective small bowel stoma. In contrast, conventional resection comprised ileocecal resection+ileocecal-ascending colon anastomosis. Postoperative complications, intraoperative and postoperative recovery, and changes in postoperative quality of life were analyzed in both groups. The severity of postoperative complications was assessed by Clavien-Dindo and the Comprehensive Complication Index (CCI). Karnofsky performance scores (KPS) were used to evaluate the quality of life of patients in the two groups preoperatively and postoperatively. The higher the KPS score, the better the quality of life.Results:Baseline patient characteristics did not differ significantly between the two groups ( P>0.05). Compared with the conventional resection group, the length of small bowel resected in the minimal bowel resection group (51 [20–200] cm vs. 91 [60–200] cm, Z=5.653, P<0.001), duration of postoperative total enteral nutrition [9 (3–18) days vs. 12 (4–50) days, Z=2.172, P=0.030], and duration of postoperative hospital stay [17 (9–24) days vs 29 (13–57) days, Z=6.424, P<0.001] were shorter; all of these differences are statistically significant. The overall incidence of postoperative complications was lower in the minimal bowel resection group than in the conventional resection group [20.0% (8/40) vs. 70.0% (28/40), χ 2=19.967, P<0.001], These comprised short bowel syndrome [5.0% (2/40) vs. 25.0% (10/40), χ 2=6.274, P=0.012], anastomotic leakage or fistula [2.5% (1/40) vs. 22.5% (9/40), χ 2=7.314, P=0.014], and pleural effusion [7.5% (3/40) vs. 25.0% (10/40), χ 2=4.500, P=0.034], all of which occurred less often in the minimal bowel resection than conventional resection group. The CCI index was also lower in the minimal bowel resection group than in the conventional resection group [CCI>40: 2.5% (1/40) vs. 12.5% (5/40), Z=18.451, P<0.001]. KPS scores were higher in the minimal bowel resection group 1 and 3 months postoperatively than they had been 1 day preoperatively (79.9±4.7 vs. 75.3±4.1, 86.2±4.8 vs. 75.3±4.1, both P<0.05). In the minimal bowel resection group, seven patients were satisfied with their current quality of life and refused to undergo stoma reduction at follow-up and one deferred stoma reduction because of rectal bleeding. The remaining 32 patients underwent stoma reduction 3 to 12 months after surgery, 26 of whom underwent ileo-cecal anastomosis. The remaining six underwent resection of the stoma and anastomosis of the ileum to the ascending colon. Conclusions:The strategy of minimal small bowel resection in patients with radiation-induced bowel injuries reduces the length of resected small bowel, decreases the risk and severity of postoperative complications, and is associated with a better prognosis and quality of life than conventional resection.
10.Effects of electrical stimulation of the sciatic nerve on the expression of vascular endothelial growth factor in the hippocampus and on learning and memory in cases of chronic cerebral hypoperfusion
Zimu HU ; Juan SONG ; Xinyi BIAN ; Jian LI ; Bohan ZHU ; Qingqin XU ; Kai ZHAO ; Xiaoping GAO
Chinese Journal of Physical Medicine and Rehabilitation 2023;45(10):878-883
Objective:To explore how electrical stimulation of the sciatic nerve affects learning and memory in cases of chronic cerebral hypoperfusion and its mechanism.Methods:Thirty-two Sprague-Dawley rats were randomly divided into a normal group, a sham-operation group, a model group and a stimulation group, each of 8. In the model and stimulation groups a chronic cerebral hypoperfusion model was established using the modified 2-VO method. The stimulation group then received electrical stimulation of the sciatic nerve for 4 weeks. Afterward all of the rats′ learning and memory were tested using the Morris water maze. HE staining and immunohistochemistry were used to observe any morphological change in the hippocampus and the expression of neuron-specific enolase (NSE) and vascular endothelial growth factor (VEGF).Results:The model and stimulation groups demonstrated significantly longer escape latency, fewer platform crossing times and shorter target quadrant times than the normal and sham-ope-ration groups before the intervention. All of these indicators had improved after the intervention. According to the HE staining, neuronal damage in the hippocampus was aggravated significantly in the model group compared with the normal and sham-operation groups, while the degree of damage was reduced in the stimulation group. Moreover, the immunohistochemistry results suggested that the expressions of NSE and VEGF were reduced significantly in the model group compared with the normal and sham-operation groups, while in the stimulation group they had increased significantly compared with the model group.Conclusions:Electrical stimulation of the sciatic nerve can improve learning and memory in cases of chronic cerebral hypoperfusion, at least in rats. It is probably related to the increased expression of VEGF in the hippocampus.

Result Analysis
Print
Save
E-mail