1.Establishment and evaluation of pendulum-like modified rat abdominal heart heterotopic transplantation model
Hongtao TANG ; Caihan LI ; Xiangyun ZHENG ; Senlin HOU ; Weiyang CHEN ; Zengwei YU ; Yabo WANG ; Dong TIAN ; Qi AN
Organ Transplantation 2025;16(2):280-287
Objective To introduce the modeling method of pendulum-like modified rat abdominal heart heterotopic transplantation model and evaluate the quality of the model. Methods An operator without transplantation experience performed 15 consecutive models, recorded the time of each step, changes in body weight and modified Stanford scores, and calculated the surgical success rate, postoperative 1-week survival rate and technical success rate. Ultrasound examinations was performed in 1 week postoperatively. Results The times for donor heart acquisition, donor heart processing, recipient preparation and transplantation anastomosis were (14.3±1.4) min, (3.5±0.6) min, (13.6±2.1) min and (38.3±5.2) min respectively. The surgical success rate was 87% (13/15), and the survival rate 1 week after operative was 100% (13/13). The improved Stanford score indicated a technical success rate of 92% (12/13), and the postoperative 1-week ultrasound examination showed that grafts with Stanford scores ≥3 had detectable pulsation and blood flow signals. Conclusions The pendulum-like modified rat abdominal heart heterotopic transplantation improved model further optimizes the operational steps with a high success rate and stable quality, may be chosen as a modeling option for basic research in heart transplantation in the future.
2.Mechanism of Alzheimer's Disease Based on Correlations between Aquaporins and Aromatic Chinese Medicines
Senlin CHEN ; Sai'e HUANG ; Zhichen WANG ; Yan LI ; Shixiang KUANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(17):227-238
Alzheimer's disease (AD) is an age-related neurodegenerative disease that belongs to the category of dementia in traditional Chinese medicine (TCM). According to the TCM theory, phlegm, dampness, stasis, and toxin are the major factors inducing the occurrence and development of AD. The application of aromatic Chinese medicines to remove the combined phlegm, dampness, stasis, and toxin is an important TCM method for treating AD. Aquaporins (AQPs) are involved in the water metabolism of the central nervous system (CNS), playing a role in the water balance of CNS. Therefore, AQPs are deeply involved in the occurrence and development of AD. AQPs may be the key targets of a variety of aromatic Chinese medicines. From the intrinsic relationship between AQPs and AD-inducing factors (phlegm, dampness, stasis, and toxin), this study explores the modern medical connotation of treating AD with aromatic Chinese medicines, aiming to provide ideas for the prevention and treatment of AD with TCM.
3.A patient with brachial artery pseudoaneurysm treated with ultrasound-guided and balloon- assisted injection of human fibrin sealant
Senlin QIAN ; Hui LI ; Ziming WAN
Chinese Journal of Nephrology 2024;40(1):53-55
The paper reports the treatment of a maintenance hemodialysis patient with pseudoaneurysm (PSA) caused by accidental injury of brachial artery during the puncture of internal fistula. The main treatment methods of PSA include surgical incision and repair, local pressure therapy, ultrasound-guided intraluminal thrombin injection, implantation of covered stent, coil embolization and so on, but they all have some defects. The patient was admitted to hospital due to poor fistula function, and the formation of brachial artery PSA was confirmed by color ultrasound. PSA was successfully treated with ultrasound-guided and balloon-assisted injection of human fibrin sealant. The fistula had good function 3 months after the operation.
4.Value of a combined ultrasound imaging radiomics model to predict progression-free survival in endocrine therapy for prostate cancer
Heyang LIU ; Qian LIU ; Hua HONG ; Diansheng JIN ; Huimin GAO ; Senlin BAO ; Wen LI
Chinese Journal of Ultrasonography 2024;33(11):992-999
Objective:To investigate the value of the combined ultrasound imaging radiomics model for predicting progression-free survival in endocrine therapy for prostate cancer.Methods:A total of 283 prostate cancer patients who received endocrine treatment at the Inner Mongolia Autonomous Region People′s Hospital and the First Hospital of Hohhot from July 2018 to January 2023 were retrospectively collected, of which 198 patients from the Inner Mongolia Autonomous Region People′s Hospital were randomly divided into the training set and the validation set according to the ratio of 7∶3, and 85 patients from the First Hospital of Hohhot served as an independent external test set. They were classified into a progression group and a non-progression group based on whether the patients progressed to desmoplasia-resistant prostate cancer 18 months after the start of endocrine treatment.Based on the two-dimensional ultrasound images, the imaging radiomics features were extracted and the imaging radiomics score (Rad-score) were constructed, the immunopathology and other clinical data were analysed, and three prediction models were constructed using logistic regression: the clinical model, the ultrasonography model, and the ultrasonography-clinical combined model, respectively. The predictive efficacy and clinical utility of the models were assessed by the ROC curves and clinical decision curves.Results:Five ultrasonographic features were included in the ultrasound model; the prostate-specific antigen nadir, the neutrophil-to-lymphocyte ratio before treatment, and the expression level of tumour proliferating cell nuclear antigen 67 (Ki-67) were incorporated into the clinical model; and the Rad score computed from the output of the ultrasound model for the screening features, together with the prostate-specific antigen nadir (PSA nadir), the neutrophil to lymphocyte ratio (NLR) before treatment, and the expression level of Ki-67 were used to construct the ultrasound-clinical joint model. The joint model achieved the highest predictive performance in both the training and validation sets of the three groups of models, with the area under the curve of 0.85 and 0.84, and the clinical decision curve showed good clinical benefit.Conclusions:The combined ultrasound-clinical model constructed in this study based on two-dimensional ultrasound images of prostate cancer before endocrine therapy can predict progression-free survival of endocrine therapy for prostate cancer more accurately.
5.Safety of high-carbohydrate fluid diet 2 h versus overnight fasting before non-emergency endoscopic retrograde cholangiopancreatography: A single-blind, multicenter, randomized controlled trial
Wenbo MENG ; W. Joseph LEUNG ; Zhenyu WANG ; Qiyong LI ; Leida ZHANG ; Kai ZHANG ; Xuefeng WANG ; Meng WANG ; Qi WANG ; Yingmei SHAO ; Jijun ZHANG ; Ping YUE ; Lei ZHANG ; Kexiang ZHU ; Xiaoliang ZHU ; Hui ZHANG ; Senlin HOU ; Kailin CAI ; Hao SUN ; Ping XUE ; Wei LIU ; Haiping WANG ; Li ZHANG ; Songming DING ; Zhiqing YANG ; Ming ZHANG ; Hao WENG ; Qingyuan WU ; Bendong CHEN ; Tiemin JIANG ; Yingkai WANG ; Lichao ZHANG ; Ke WU ; Xue YANG ; Zilong WEN ; Chun LIU ; Long MIAO ; Zhengfeng WANG ; Jiajia LI ; Xiaowen YAN ; Fangzhao WANG ; Lingen ZHANG ; Mingzhen BAI ; Ningning MI ; Xianzhuo ZHANG ; Wence ZHOU ; Jinqiu YUAN ; Azumi SUZUKI ; Kiyohito TANAKA ; Jiankang LIU ; Ula NUR ; Elisabete WEIDERPASS ; Xun LI
Chinese Medical Journal 2024;137(12):1437-1446
Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.
6.The prognostic value of colonoscopy grading for acute graft-versus-host disease in patients with malignant hematological disorders after unrelated cord blood transplantation
Senlin WANG ; Guangyu SUN ; Xiaoyu ZHU ; Xuemei XU ; Fei YE ; Shilan LI ; Si CHEN
Chinese Journal of Hematology 2024;45(5):462-467
Objective:To investigate the prognostic value of enteroscopic grading for the prognostic assessment of patients with malignant hematological diseases who developed intestinal acute graft-versus-host disease (IT-aGVHD) after unrelated cord blood transplantation (UCBT) .Methods:Fifty patients with IT-aGVHD who developed hormone resistance after UCBT from June 2016 to June 2023 at Anhui Provincial Hospital were collected to compare the effective and survival rates of IT-aGVHD treatment in the group with milder enteroscopic mucosal injury (27 cases, enteroscopic grading of Ⅰ and Ⅱ) and the group with more severe injury (23 cases, enteroscopic grading of Ⅲ and Ⅳ) and to retrospectively analyze the factors affecting patients’ prognosis.Results:Patients in the mild and severe groups had an effective rate of 92.6% and 47.8% at 28 days after colonoscopy ( P<0.001), 81.5% and 39.1% at 56 days after colonoscopy ( P=0.002), with optimal effective rate of 92.6% and 65.2% ( P=0.040), respectively, and the differences were statistically significant. The multifactorial analysis found that enteroscopic grading was an independent risk factor affecting the effective rate of IT-aGVHD treatment. The overall survival rate at 2 years after colonoscopy was 70.4% (95% CI 52.0% -88.8% ) and 34.8% (95% CI 14.8% -54.8% ) for patients in the mild and severe groups, respectively, and the difference was statistically significant ( P=0.003). Multifactorial analysis revealed that enteroscopic grading, cytomegalovirus infection status, second-line treatment regimen, and patients’ age were independent risk factors for survival. Conclusion:The treatment efficacy and prognosis of patients in the group with less severe enteroscopic injury (grades Ⅰ and Ⅱ) were better than those in the group with more severe injury (grades Ⅲ and Ⅳ) .
7.Monte Carlo simulation of α recoil migration of plutonium aerosol
Chuanlong LI ; Jinsen GUO ; Chuangao WANG ; Hongchao PANG ; Senlin LIU
Chinese Journal of Radiological Health 2023;32(4):398-401
Objective To evaluate the migration of plutonium aerosol caused by α recoil. Methods In this paper, the recoil deposition and Brownian motion of plutonium-containing nanoaerosols were simulated by Monte Carlo method. The recoil angle and the vertical first landing time of Brownian motion in the process of settling were sampled, and then the lateral displacements of Brownian motion were sampled to determine the final settling position of aerosol. Results For aerosols with particle sizes of 10-50 nm, the maximum migration distance of a single recoil settling was 1.39 μm. Brownian motion increased the migration capacity. Although there was a high likelihood that aerosols settled within 100 μm, there remained a slight probability of long-term suspension in the air. Conclusion The α recoil is one of the mechanisms of plutonium aerosol migration. An important mechanism for long-distance migration of nanoaerosols is that Brownian motion after recoil may cause them to suspend for a long time.
8.Clinical characteristics of choledocholithiasis combined with periampullary diverticulum and influencing factor analysis for difficult cannulation of endoscopic retrograde cholangiopan-creatography: a report of 1 920 cases
Ping YUE ; Zhenyu WANG ; Leida ZHANG ; Hao SUN ; Ping XUE ; Wei LIU ; Qi WANG ; Jijun ZHANG ; Xuefeng WANG ; Meng WANG ; Yingmei SHAO ; Kailin CAI ; Senlin HOU ; Kai ZHANG ; Qiyong LI ; Lei ZHANG ; Kexiang ZHU ; Haiping WANG ; Ming ZHANG ; Xiangyu SUN ; Zhiqing YANG ; Jie TAO ; Zilong WEN ; Qunwei WANG ; Bendong CHEN ; Yingkai WANG ; Mingning ZHAO ; Ruoyan ZHANG ; Tiemin JIANG ; Ke LIU ; Lichao ZHANG ; Kangjie CHEN ; Xiaoliang ZHU ; Hui ZHANG ; Long MIAO ; Zhengfeng WANG ; Jiajia LI ; Xiaowen YAN ; Ling'en ZHANG ; Fangzhao WANG ; Wence ZHOU ; Wenbo MENG ; Xun LI
Chinese Journal of Digestive Surgery 2023;22(1):113-121
Objective:To investigate the clinical characteristics of choledocholithiasis com-bined with periampullary diverticulum and influencing factor for difficult cannulation of endoscopic retrograde cholangiopancreatography (ERCP).Methods:The retrospective case-control study was conducted. The clinical data of 1 920 patients who underwent ERCP for choledocholithiasis in 15 medical centers, including the First Hospital of Lanzhou University, et al, from July 2015 to December 2017 were collected. There were 915 males and 1 005 females, aged (63±16)years. Of 1 920 patients, there were 228 cases with periampullary diverticulum and 1 692 cases without periampullary diverticulum. Observation indicators: (1) clinical characteristics of patients with choledocholithiasis; (2) intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis; (3) influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and com-parison between groups was conducted using the Wilcoxon rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. The Logistic regression model was used for univariate and multivariate analyses. Results:(1) Clinical characteristics of patients with choledocholithiasis. Age, body mass index, cases with complications as chronic obstructive pulmonary disease, diameter of common bile duct, cases with diameter of common bile duct as <8 mm, 8?12 mm, >12 mm, diameter of stone, cases with number of stones as single and multiple were (69±12)years, (23.3±3.0)kg/m 2, 16, (14±4)mm, 11, 95, 122, (12±4)mm, 89, 139 in patients with choledocholithiasis combined with periampullary diverticulum, versus (62±16)years, (23.8±2.8)kg/m 2, 67, (12±4)mm, 159, 892, 641, (10±4)mm, 817, 875 in patients with choledocholithiasis not combined with periampullary diver-ticulum, showing significant differences in the above indicators between the two groups ( t=?7.55, 2.45, χ2=4.54, t=?4.92, Z=4.66, t=?7.31, χ2=6.90, P<0.05). (2) Intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis. The balloon expansion diameter, cases with intraoperative bleeding, cases with hemorrhage management of submucosal injection, hemostatic clip, spray hemostasis, electrocoagulation hemostasis and other treatment, cases with endoscopic plastic stent placement, cases with endoscopic nasal bile duct drainage, cases with mechanical lithotripsy, cases with stone complete clearing, cases with difficult cannulation, cases with delayed intubation, cases undergoing >5 times of cannulation attempts, cannulation time, X-ray exposure time, operation time were 10.0(range, 8.5?12.0)mm, 56, 6, 5, 43, 1, 1, 52, 177, 67, 201, 74, 38, 74, (7.4±3.1)minutes, (6±3)minutes, (46±19)minutes in patients with choledocholithiasis combined with periampullary diverticulum, versus 9.0(range, 8.0?11.0)mm, 243, 35, 14, 109, 73, 12, 230, 1 457, 167, 1 565, 395, 171, 395, (6.6±2.9)minutes, (6±5)minutes, (41±17)minutes in patients with choledocholithiasis not combined with periampullary diverticulum, showing significant differences in the above indicators between the two groups ( Z=6.31, χ2=15.90, 26.02, 13.61, 11.40, 71.51, 5.12, 9.04, 8.92, 9.04, t=?3.89, 2.67, ?3.61, P<0.05). (3) Influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Results of multivariate analysis showed total bilirubin >30 umol/L, number of stones >1, combined with periampullary diverticulum were indepen-dent risk factors for difficult cannulation in patients with periampullary diverticulum who underwent ERCP for choledocholithiasis ( odds ratio=1.31, 1.48, 1.44, 95% confidence interval as 1.06?1.61, 1.20?1.84, 1.06?1.95, P<0.05). Results of further analysis showed that, of 1 920 patients undergoing ERCP for choledocholithiasis, the incidence of postoperative pancreatitis was 17.271%(81/469) and 8.132%(118/1 451) in the 469 cases with difficult cannulation and 1 451 cases without difficult cannula-tion, respectively, showing a significant difference between them ( χ2=31.86, P<0.05). In the 1 692 patients with choledocholithiasis not combined with periampullary diverticulum, the incidence of postopera-tive pancreatitis was 17.722%(70/395) and 8.250%(107/1 297) in 395 cases with difficult cannula-tion and 1 297 cases without difficult cannulation, respectively, showing a significant difference between them ( χ2=29.00, P<0.05). In the 228 patients with choledocholithiasis combined with peri-ampullary diverticulum, the incidence of postoperative pancreatitis was 14.865%(11/74) and 7.143%(11/154) in 74 cases with difficult cannulation and 154 cases without difficult cannulation, respectively, showing no significant difference between them ( χ2=3.42, P>0.05). Conclusions:Compared with patients with choledocholithiasis not combined with periampullary divertioulum, periampullary divertioulum often occurs in choledocholithiasis patients of elderly and low body mass index. The proportion of chronic obstructive pulmonary disease is high in choledocholithiasis patients with periampullary diverticulum, and the diameter of stone is large, the number of stone is more in these patients. Combined with periampullary diverticulum will increase the difficult of cannulation and the ratio of patient with mechanical lithotripsy, and reduce the ratio of patient with stone complete clearing without increasing postoperative complications of choledocholithiasis patients undergoing ERCP. Total bilirubin >30 μmol/L, number of stones >1, combined with periampullary diverticulum are independent risk factors for difficult cannulation in patients of periampullary diverticulum who underwent ERCP for choledocholithiasis.
9.Nanoparticles (NPs)-mediated systemic mRNA delivery to reverse trastuzumab resistance for effective breast cancer therapy.
Zhihui DONG ; Zhuoshan HUANG ; Senlin LI ; Ying WANG ; Yandan YAO ; Xianzhu YANG ; Xiaoding XU
Acta Pharmaceutica Sinica B 2023;13(3):955-966
Monoclonal antibody-based therapy has achieved great success and is now one of the most crucial therapeutic modalities for cancer therapy. The first monoclonal antibody authorized for treating human epidermal growth receptor 2 (HER2)-positive breast cancer is trastuzumab. However, resistance to trastuzumab therapy is frequently encountered and thus significantly restricts the therapeutic outcomes. To address this issue, tumor microenvironment (TME) pH-responsive nanoparticles (NPs) were herein developed for systemic mRNA delivery to reverse the trastuzumab resistance of breast cancer (BCa). This nanoplatform is comprised of a methoxyl-poly (ethylene glycol)-b-poly (lactic-co-glycolic acid) copolymer with a TME pH-liable linker (Meo-PEG-Dlink m -PLGA) and an amphiphilic cationic lipid that can complex PTEN mRNA via electrostatic interaction. When the long-circulating mRNA-loaded NPs build up in the tumor after being delivered intravenously, they could be efficiently internalized by tumor cells due to the TME pH-triggered PEG detachment from the NP surface. With the intracellular mRNA release to up-regulate PTEN expression, the constantly activated PI3K/Akt signaling pathway could be blocked in the trastuzumab-resistant BCa cells, thereby resulting in the reversal of trastuzumab resistance and effectively suppress the development of BCa.
10.Concurrent silencing of TBCE and drug delivery to overcome platinum-based resistance in liver cancer.
Senlin LI ; Siyu CHEN ; Zhihui DONG ; Xingdong SONG ; Xiuling LI ; Ziqi HUANG ; Huiru LI ; Linzhuo HUANG ; Ganyuan ZHUANG ; Ran LAN ; Mingyan GUO ; Wende LI ; Phei Er SAW ; Lei ZHANG
Acta Pharmaceutica Sinica B 2023;13(3):967-981
Platinum-based chemotherapy resistance is a key factor of poor prognosis and recurrence in hepatocellular carcinoma (HCC). Herein, RNAseq analysis revealed that elevated tubulin folding cofactor E (TBCE) expression is associated with platinum-based chemotherapy resistance. High expression of TBCE contributes to worse prognoses and earlier recurrence among liver cancer patients. Mechanistically, TBCE silencing significantly affects cytoskeleton rearrangement, which in turn increases cisplatin-induced cycle arrest and apoptosis. To develop these findings into potential therapeutic drugs, endosomal pH-responsive nanoparticles (NPs) were developed to simultaneously encapsulate TBCE siRNA and cisplatin (DDP) to reverse this phenomena. NPs (siTBCE + DDP) concurrently silenced TBCE expression, increased cell sensitivity to platinum treatment, and subsequently resulted in superior anti-tumor effects both in vitro and in vivo in orthotopic and patient-derived xenograft (PDX) models. Taken together, NP-mediated delivery and the co-treatment of siTBCE + DDP proved to be effective in reversing chemotherapy resistance of DDP in multiple tumor models.

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