1.Clinicopathological features and prognosis of 117 cases of fumarate hydratase-deficient uterine leiomyomas
Wennian YU ; Siyi PAN ; Cong WANG ; Zhendong HUANG ; Xianglian WANG ; Shu ZHU ; Yan DING ; Xiuli WANG
Chinese Journal of Obstetrics and Gynecology 2025;60(6):450-460
Objective:To explore the clinicopathological characteristics and prognosis of fumarate hydratase-deficient uterine leiomyoma (FH-dUL).Methods:Clinical data and follow-up information for 117 patients with FH-dUL diagnosed through surgical pathology and immunohistochemistry in the First Affiliated Hospital of Nanjing Medical University from January 2020 to December 2024, were collected. A control group of 130 patients with common uterine leiomyomas was also included. The differences between the two groups in clinical, imaging, and pathological characteristics were compared. Additionally, recurrence rates, fertility outcomes for FH-dUL patients, and the incidence of renal cancer in FH germline mutation carriers were monitored.Results:(1) Comparison of clinicopathological characteristics: the median age of 117 FH-dUL patients was 35 years, and the median age at first diagnosis of uterine leiomyomas was 29 years, both significantly younger than the control group (41 and 36 years; both P<0.01). The FH-dUL group showed significantly higher incidences of uterine myomectomy, multiple leiomyomas, diffusion restriction on pelvic magnetic resonance imaging diffusion weighted imaging, and typical pathological features (candelabra-like vessels, bizarre nuclei, cytoplasmic eosinophilic globules, perinuclear halo, cellular atypia) and higher ultrasound blood flow score (all P<0.05). Of the 30 FH-dUL patients who underwent genetic testing, 9 had germline mutations, 3 had somatic mutations, and 6 had mutations of unclear origin. Among the 9 FH gene germline mutation patients, 2 had already developed renal cell carcinoma. (2) Recurrence analysis: among the 56 patients who underwent uterine myomectomy, 22 (39.3%, 22/56) experienced recurrence during follow-up, compared to 12 (21.8%, 12/55) of the 55 patients in the control group, the difference between the two groups was statistically significant ( P=0.046). Multivariate binary logistic regression analysis showed that cellular leiomyomas ( OR=9.489, 95% CI: 1.740-51.755; P=0.009) and multiple uterine leiomyomas ( OR=10.709, 95% CI: 1.354-84.683; P=0.025) were significant risk factors for recurrence in FH-dUL. (3) Fertility analysis: among the 66 FH-dUL patients who underwent fertility-preserving surgery, 16 had the intention to have fertility desire, only 2 (2/16) completed their fertility plans during follow-up. Conclusions:Clinicopathological features and imaging features help to differentiate FH-dUL from common type uterine fibroids, but lack specificity, and the diagnosis of FH-dUL is based on immunohistochemistry. The recurrence rate after resection of FH-dUL is high, and cellular and multiple leiomyomas are important predictors of recurrence. It is crucial to perform genetic testing, genetic counseling, drug treatment to prevent recurrence, fertility guidance, and long-term comprehensive management after surgery for FH-dUL management.
2.Effects of calcium alginate-chlorella hydrogel combined with microwave thermotherapy on proliferation, apoptosis and immune activation of pancreatic cancer cells
Chengye PAN ; Donghao CAI ; Tinglin ZHANG ; Jie GAO ; Kaixuan WANG ; Zhendong JIN
Chinese Journal of Pancreatology 2025;25(2):90-96
Objective:To construct a calcium alginate (ALG-Ca 2+) composite hydrogel loaded with chlorella protein (Cp) (ALG-Ca 2+@Cp) and investigate its combined effect with microwave hyperthermia on the proliferation, apoptosis, and immune activation of mouse pancreatic cancer cells. Methods:ALG-Ca 2+@Cp was prepared using a physical cross-linking method and its physiochemical properties was characterized via scanning electron microscopy, rheological analysis, Ca 2+ release experiments, and microwave thermal conversion tests. The BCA protein quantification assay was used to evaluate the adsorption capacity of ALG-Ca 2+@Cp for pancreatic cancer cell antigens. The effects of ALG-Ca 2+@Cp extract combined with microwave intervention on pancreatic cancer cell proliferation, apoptosis protein expression, and cell viability were assessed using CCK-8 assays, ELISA, and Calcein-AM/PI double fluorescence staining. Flow cytometry was performed to determine the maturation-promoting ability of ALG-Ca 2+@Cp on immature mouse bone marrow-derived dendritic cells (BMDCs). Results:ALG-Ca 2+@Cp exhibited a three-dimensional network structure with a storage modulus (G') greater than the loss modulus (G''), demonstrating typical hydrogel properties. The hydrogel loaded with 0.5 mol/ml Ca 2+ reached 48°C after 5 minutes of microwave irradiation at 5.0 W/cm 2, and Ca 2+ release plateaued within 5 minutes. ALG-Ca 2+@Cp effectively adsorbed pancreatic cancer cell antigens. Combined with microwave treatment, it significantly reduced pancreatic cancer cell proliferation ( A450 value 0.39±0.07 vs 2.78±0.15) and increased apoptosis markers calreticulin (CRT) and high mobility group box-1 protein (HMGB1) [(557.09±37.84) pg/ml vs (135.14±11.84) pg/ml, (4.77±0.18) ng/ml vs (1.6±0.16) ng/ml], leading to decreased cell viability; and all the differences were statistically significant (all P value <0.05). ALG-Ca 2+@Cp synergistically promoted the maturation of immature BMDCs in the presence of pancreatic cancer antigens, with a CD 80+ positivity rate of (75.67±6.53)%. Conclusions:ALG-Ca 2+@Cp is successfully constructed. Its combination with microwave hyperthermia can significantly enhance the cytotoxicity and immune activation against mouse pancreatic cancer cells by targeting intracellular antigens and inducing immunogenic cell death.
3.Clinicopathological features and prognosis of 117 cases of fumarate hydratase-deficient uterine leiomyomas
Wennian YU ; Siyi PAN ; Cong WANG ; Zhendong HUANG ; Xianglian WANG ; Shu ZHU ; Yan DING ; Xiuli WANG
Chinese Journal of Obstetrics and Gynecology 2025;60(6):450-460
Objective:To explore the clinicopathological characteristics and prognosis of fumarate hydratase-deficient uterine leiomyoma (FH-dUL).Methods:Clinical data and follow-up information for 117 patients with FH-dUL diagnosed through surgical pathology and immunohistochemistry in the First Affiliated Hospital of Nanjing Medical University from January 2020 to December 2024, were collected. A control group of 130 patients with common uterine leiomyomas was also included. The differences between the two groups in clinical, imaging, and pathological characteristics were compared. Additionally, recurrence rates, fertility outcomes for FH-dUL patients, and the incidence of renal cancer in FH germline mutation carriers were monitored.Results:(1) Comparison of clinicopathological characteristics: the median age of 117 FH-dUL patients was 35 years, and the median age at first diagnosis of uterine leiomyomas was 29 years, both significantly younger than the control group (41 and 36 years; both P<0.01). The FH-dUL group showed significantly higher incidences of uterine myomectomy, multiple leiomyomas, diffusion restriction on pelvic magnetic resonance imaging diffusion weighted imaging, and typical pathological features (candelabra-like vessels, bizarre nuclei, cytoplasmic eosinophilic globules, perinuclear halo, cellular atypia) and higher ultrasound blood flow score (all P<0.05). Of the 30 FH-dUL patients who underwent genetic testing, 9 had germline mutations, 3 had somatic mutations, and 6 had mutations of unclear origin. Among the 9 FH gene germline mutation patients, 2 had already developed renal cell carcinoma. (2) Recurrence analysis: among the 56 patients who underwent uterine myomectomy, 22 (39.3%, 22/56) experienced recurrence during follow-up, compared to 12 (21.8%, 12/55) of the 55 patients in the control group, the difference between the two groups was statistically significant ( P=0.046). Multivariate binary logistic regression analysis showed that cellular leiomyomas ( OR=9.489, 95% CI: 1.740-51.755; P=0.009) and multiple uterine leiomyomas ( OR=10.709, 95% CI: 1.354-84.683; P=0.025) were significant risk factors for recurrence in FH-dUL. (3) Fertility analysis: among the 66 FH-dUL patients who underwent fertility-preserving surgery, 16 had the intention to have fertility desire, only 2 (2/16) completed their fertility plans during follow-up. Conclusions:Clinicopathological features and imaging features help to differentiate FH-dUL from common type uterine fibroids, but lack specificity, and the diagnosis of FH-dUL is based on immunohistochemistry. The recurrence rate after resection of FH-dUL is high, and cellular and multiple leiomyomas are important predictors of recurrence. It is crucial to perform genetic testing, genetic counseling, drug treatment to prevent recurrence, fertility guidance, and long-term comprehensive management after surgery for FH-dUL management.
4.Effects of calcium alginate-chlorella hydrogel combined with microwave thermotherapy on proliferation, apoptosis and immune activation of pancreatic cancer cells
Chengye PAN ; Donghao CAI ; Tinglin ZHANG ; Jie GAO ; Kaixuan WANG ; Zhendong JIN
Chinese Journal of Pancreatology 2025;25(2):90-96
Objective:To construct a calcium alginate (ALG-Ca 2+) composite hydrogel loaded with chlorella protein (Cp) (ALG-Ca 2+@Cp) and investigate its combined effect with microwave hyperthermia on the proliferation, apoptosis, and immune activation of mouse pancreatic cancer cells. Methods:ALG-Ca 2+@Cp was prepared using a physical cross-linking method and its physiochemical properties was characterized via scanning electron microscopy, rheological analysis, Ca 2+ release experiments, and microwave thermal conversion tests. The BCA protein quantification assay was used to evaluate the adsorption capacity of ALG-Ca 2+@Cp for pancreatic cancer cell antigens. The effects of ALG-Ca 2+@Cp extract combined with microwave intervention on pancreatic cancer cell proliferation, apoptosis protein expression, and cell viability were assessed using CCK-8 assays, ELISA, and Calcein-AM/PI double fluorescence staining. Flow cytometry was performed to determine the maturation-promoting ability of ALG-Ca 2+@Cp on immature mouse bone marrow-derived dendritic cells (BMDCs). Results:ALG-Ca 2+@Cp exhibited a three-dimensional network structure with a storage modulus (G') greater than the loss modulus (G''), demonstrating typical hydrogel properties. The hydrogel loaded with 0.5 mol/ml Ca 2+ reached 48°C after 5 minutes of microwave irradiation at 5.0 W/cm 2, and Ca 2+ release plateaued within 5 minutes. ALG-Ca 2+@Cp effectively adsorbed pancreatic cancer cell antigens. Combined with microwave treatment, it significantly reduced pancreatic cancer cell proliferation ( A450 value 0.39±0.07 vs 2.78±0.15) and increased apoptosis markers calreticulin (CRT) and high mobility group box-1 protein (HMGB1) [(557.09±37.84) pg/ml vs (135.14±11.84) pg/ml, (4.77±0.18) ng/ml vs (1.6±0.16) ng/ml], leading to decreased cell viability; and all the differences were statistically significant (all P value <0.05). ALG-Ca 2+@Cp synergistically promoted the maturation of immature BMDCs in the presence of pancreatic cancer antigens, with a CD 80+ positivity rate of (75.67±6.53)%. Conclusions:ALG-Ca 2+@Cp is successfully constructed. Its combination with microwave hyperthermia can significantly enhance the cytotoxicity and immune activation against mouse pancreatic cancer cells by targeting intracellular antigens and inducing immunogenic cell death.
5.Effect of remimazolam on anesthetic efficacy of painless bronchoscopy in elderly patients
Xuehu ZHANG ; Zhendong XU ; Peipei CHEN ; Juncheng XIONG ; Zonghuai PAN
China Modern Doctor 2024;62(3):78-82
Objective To investigate the effect of remimazolam on anesthetic effect and postoperative cognitive function during painless bronchoscopy in elderly patients.Methods A total of 90 patients with painless bronchoscopy admitted to Wenzhou People's Hospital were selected.And randomly dividing into 45 patients in control group,45 patients in observation group.The control group was given propofol,and the observation group was given remimazolam.Mean arterial pressure(MAP),heart rate(HR),and blood oxygen saturation(SpO2)were monitored.Effective time after induction,recovery time after withdrawal and discharge time were compared.Patient's cognitive function was assessed using the mini-mental state examination(MMSE),auditory word learning test(AVLT),shape connection test(STT),and animal language fluency test(AFT).Enzyme linked immunosorbent assay(ELISA)was used to determine substance P(SP),C-reactive protein(CRP),noradrenaline(NE),tumor necrosis factor-α(TNF-α)in serum,interleukin(IL)-6 and prostaglandin E2(PGE2)concentrations.Results Compared with the control group,the MAP of the observation group patients at time points T2 and T3 showed statistically significant differences(P<0.05);HR was especially significant at T2,T3 and T6 periods(P<0.05).SpO2 at T2 and T3(P<0.05).The awakening time,discharge time of the observation were shorter than control(P<0.05).At 1 day after surgery,the MMSE score,STT score,AFT score were significantly higher(P<0.05);The serum levels of SP,PGE2 and NE and IL-6,TNF-α and CRP were decreased in the control(P<0.05).The incidence of adverse reactions was 17.78%in control group and 8.89%in observation group(χ2=7.654,P=0.031).Conclusion Remazolam is used in painless bronchoscopy in elderly patients,intraoperative hemodynamics is stable,having little impact on postoperative cognitive function,and inhibits the release of inflammatory factors and the secretion of pain mediators,which is worthy of clinical use.
6.Analysis of Animal Models of Post-infectious Irritable Bowel Syndrome Based on Characteristics of Clinical Symptoms of Traditional Chinese and Western Medicine
Lu'an XIE ; Yangyu ZHANG ; Xiaoxia CHEN ; Zhendong PAN ; Yiling YANG ; Shi HUANG
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(1):92-102
Objective This paper summarizes and evaluates the existing animal models of Post-infectious irritable bowel syndrome(PI-IBS)based on the clinical diagnostic criteria and symptom characteristics of PI-IBS in Chinese and western medicine.The goal of this study is to seek out animal models with a high degree of clinical agreement between Chinese and western medicine,and to provide an accurate animal model for the prevention and treatment of PI-IBS in traditional Chinese medicine.Methods The animal strains,modelling methods,and mechanisms of the existing PI-IBS animal models were summarized based on the clinical diagnostic features and symptomatology of PI-IBS,as well as the degree of match was evaluated and the strengths and weaknesses of the preparation of animal models were analyzed,by reviewing the articles related to PI-IBS animal experiments and the preparation of animal models.Results A thorough analysis discovered that Campylobacter jejuni infection model,Trichinella infection model,and liver depression and spleen deficiency syndrome in models of disease and symptom combination showed a comparatively high level of clinical agreement between Chinese and western medicine.Conclusion The existing PI-IBS models had the high degree of coincidence with western medicine,Chinese medicine four diagnoses and syndrome are generally less embodied and collected in the modeling process.The primary symptoms in Chinese medicine diagnosis are primarily based on the observation of animal apparent behaviors,while the observation of the sub-syndrome manifestations is relatively less,which results in failure of judgment of TCM syndrome types.Therefore,it is still necessary to further standardize the criteria for evaluating symptoms and the techniques for identifying disease-syndrome combination animal models.PI-IBS model with the syndrome-clinical characteristics in Chinese and western medicine has significant application value and prospects in the future.The multifactorial composite method of western medicine pathological injury+Chinese medicine etiological stimulation can establish a PI-IBS model with a higher degree of coincidence,which can provide theoretical support for the study of the pathogenesis of PI-IBS,the difference of syndrome,and the prevention and treatment with integrative Chinese and western medicine.It is crucial to guide the clinical diagnosis and treatment of PI-IBS.
7.Rapid screening of SARS-CoV-2 inhibitors via ratiometric fluorescence of RBD-ACE2 complexes in living cells by competitive binding.
Lu MIAO ; Wei ZHOU ; Chunyu YAN ; Yuebin ZHANG ; Qinglong QIAO ; Xuelian ZHOU ; Yingzhu CHEN ; Guangying WANG ; Zhendong GUO ; Jun LIU ; Hailong PIAO ; Xia PAN ; Mengxue YAN ; Weijie ZHAO ; Guohui LI ; Yueqing LI ; Zhaochao XU
Acta Pharmaceutica Sinica B 2022;12(9):3739-3742
8.Clinical application value of endoscopic ultrasound in the etiological diagnosis of idiopathic acute pancreatitis
Xue PAN ; Jie GAO ; Yunfeng WANG ; Ting YANG ; Zenghui DOU ; Zhendong JIN
Chinese Journal of Pancreatology 2022;22(4):267-271
Objective:To evaluate the clinical application value of endoscopic ultrasonography (EUS) in the etiological diagnosis of patients initially diagnosed with idiopathic acute pancreatitis (IAP).Methods:Clinical data of 128 patients who underwent further EUS and magnetic resonance cholangiopancreatography (MRCP) after initial diagnosis of IAP at the Gastrointestinal Endoscopy Center of the First Affiliated Hospital of Naval Medical University between January 2015 and February 2022 were collected and divided into a single-episode group (single-episode group, 51 cases) and a multiple-episode group (recurrent group, 77 cases) based on the number of AP episodes. The data and the diagnosis of the etiology of IAP in the two groups by EUS were analyzed and compared with the etiological diagnosis results of MRCP.Results:The differences on basic information such as gender, age, history of smoking, history of alcohol consumption, family history of pancreatic disease, history of cholecystectomy, abnormality of liver function, and severity of pancreatitis between the single-episode group and recurrent group of IAP patients were not statistically significant. The etiology was clarified in 79 (62%) IAP patients after EUS examination, of which 55 (43%) cases had biliary disease (gallstones, microlithiasis, biliary sludge) and 24 (19%) cases had pancreatic disease (chronic pancreatitis, pancreatic divisum, pancreatic interstitial or pancreatic ductal changes). The percentage of patients with biliary disease as the cause of IAP was significantly higher in the single-episode group than in the recurrent group (59% vs 32%), while the percentage of patients with pancreatic disease as the cause of IAP was higher in the recurrent group than in the single-episode group (25% vs 10%), with statistically significant differences ( P values=0.004 and 0.035, respectively). The performance of EUS in diagnosing the etiology of IAP was significantly higher than that of MRCP (62% vs 19%, P=0.032), where EUS was more accurate in detecting biliary microlithiasis or biliary sludge (43% vs 9%, P<0.01). EUS was also superior to MRCP in identifying subtle changes in chronic pancreatitis lesions (small pancreatic nodules, patchy hyperechogenicity, etc.) and intraductal papillary mucinous neoplasms(17% vs 7%, P<0.05), but was inferior to MRCP in identifying pancreatic divisum (2 cases vs 4 cases). Conclusions:In view of high diagnostic accuracy and safety of EUS in diagnosing biliary diseases, and based on the fact that most IAPs in China are due to biliary diseases, EUS based management strategy can be considered to be a reasonable approach for evaluation of IAP patients. The MRCP can be used as a supplement to the EUS to identify a controversial etiology.
9.Diagnostic value of contrast-enhanced harmonic endoscopic ultrasonography for pancreatic cystic lesions
Xue PAN ; Jie GAO ; Yunfeng WANG ; Zenghui DU ; Zhendong JIN
Chinese Journal of Pancreatology 2021;21(2):103-106
Objective:To evaluate diagnostic value of contrast-enhanced harmonic endoscopic ultrasonography (CEH-EUS) for pancreatic cystic lesions.Methods:Endoscopic and clinical follow-up data of patients with pancreatic cystic lesions diagnosed by EUS in Department of Gastroenterology of the First Affiliated Hospital of Naval Medical University with CEH-EUS video from March 2013 to April 2020 was retrospectively analyzed.Results:A total of 36 patients were included. There were 16 cases of serous cystadenomas (SCA), 10 cases of mucinous cystic neoplasm (MCN), 5 cases of intraductal papillary mucinous neoplasms (IPMN, 3 with complex type, 2 with main pancreatic duct type) and 5 cases of pancreatic pseudocyst (PPC). 87.5%(14/16) of SCA and 86.7%(13/15) of MCN+ IPMN had hyperenhanced cystic wall with obvious peak and similar washout as surrounding tissue, whereas only 20%(1/5) PPC had hyperenhanced cystic wall. The hyperenhancing effect of PPC was significantly lower than that of SCA and MCN+ IPMN ( P=0.0035 and P=0.0048, respectively ). Mural nodules were detected in 17 cases of pancreatic cystic lesions by EUS, of which 3 cases had hyperenhanced mural modules and 14 cases had hypoenhanced mural nodules by CEH-EUS. Patients showing hyperenhanced mural modules were all finally diagnosed as pancreatic malignancy (1 IPMN, 2 MCN), and the accuracy was 100%. Conclusions:CEH-EUS can have a obvious advantage of differentiating pseudocyst and other pancreatic cystic lesions, while not very useful for differentiating SCA and MCN. Pancreatic cystic lesions showing hyperenhanced mural nodules under CEH-EUS may imply malignancy potential.
10.An experimental study of EUS-guided radiofrequency ablation of porcine pancreas in vitro
Peng PAN ; Dong WANG ; Zhaoshen LI ; Lei WANG ; Huagao ZHANG ; Ke QI ; Zhendong JIN
Chinese Journal of Pancreatology 2014;14(5):312-315
Objective To investigate the extent of radiofrequency ablation of pig pancreas in vitro with various power and duration,and to establish the regression equation of radiofrequency ablation of porcine pancreas in vitro.Methods Among the 4 settings of power (from 5 w ~ 20 w) and 11 settings of duration (from 40s ~ 240s),44 combinations were selected,and every combination was performed twice,then a randomization table including 88 combinations was established,and 88 ablation procedures on porcine pancreases in vitro were performed.The uhrasonography changes were observed,ablation widths (Y) were measured,and pathological examination was performed.In order to construct optimal model and to establish the regression equation of radiofrequency ablation,9 parameters (duration,power,duration × power,the square of duration,the square of power,the square root of duration,the square root of power,the natural logarithm of duration,the natural logarithm of power) derived from duration and power were analyzed via stepwise regression method.Results A rectangular echo enhanced region was observed along the working area of catheter when radiofrequency ablation started,and it gradually became wider during ablation.A hoar-like cylindrical ablation region that was clearly different from surrounding normal pancreatic tissue was formed.Carbonation of necrotic tissue could be observed after radiofrequency ablation under 15 w or 20 w.The optimal model showed a linear positive correlation between ablation width (Y) with the square of power and the natural logarithm of duration.The coefficient of determination of this model was 0.71.Both Fitting curve and Residual scatter diagram showed good fitting effect.Finally,a significant regression equation of radiofrequency ablation was established:Y (mm) =0.005 × E2 + 0.9374 × ln (t)-0.6943.Conclusions A significant regression equation of radiofrequency ablation is established,which provides experimental base for EUS-guided radiofrequency ablation of pancreatic tumors in clinical practice.

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