1.Artificial intelligence predicts direct-acting antivirals failure among hepatitis C virus patients: A nationwide hepatitis C virus registry program
Ming-Ying LU ; Chung-Feng HUANG ; Chao-Hung HUNG ; Chi‐Ming TAI ; Lein-Ray MO ; Hsing-Tao KUO ; Kuo-Chih TSENG ; Ching-Chu LO ; Ming-Jong BAIR ; Szu-Jen WANG ; Jee-Fu HUANG ; Ming-Lun YEH ; Chun-Ting CHEN ; Ming-Chang TSAI ; Chien-Wei HUANG ; Pei-Lun LEE ; Tzeng-Hue YANG ; Yi-Hsiang HUANG ; Lee-Won CHONG ; Chien-Lin CHEN ; Chi-Chieh YANG ; Sheng‐Shun YANG ; Pin-Nan CHENG ; Tsai-Yuan HSIEH ; Jui-Ting HU ; Wen-Chih WU ; Chien-Yu CHENG ; Guei-Ying CHEN ; Guo-Xiong ZHOU ; Wei-Lun TSAI ; Chien-Neng KAO ; Chih-Lang LIN ; Chia-Chi WANG ; Ta-Ya LIN ; Chih‐Lin LIN ; Wei-Wen SU ; Tzong-Hsi LEE ; Te-Sheng CHANG ; Chun-Jen LIU ; Chia-Yen DAI ; Jia-Horng KAO ; Han-Chieh LIN ; Wan-Long CHUANG ; Cheng-Yuan PENG ; Chun-Wei- TSAI ; Chi-Yi CHEN ; Ming-Lung YU ;
Clinical and Molecular Hepatology 2024;30(1):64-79
Background/Aims:
Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy.
Methods:
We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment.
Results:
The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset.
Conclusions
Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.
2.Clinical application of robotic-assistant living donor left lateral segmentectomy
Yamin ZHANG ; Wei GAO ; Zilin CUI ; Chong DONG ; Rui FENG ; Chao SUN ; Yi BAI ; Zhongyang SHEN
Chinese Journal of Organ Transplantation 2023;44(6):339-345
Objective:To explore the feasibility and safety of robotic-assisted living donor left lateral segmentectomy (LDLLS) in a large pediatric liver transplant program.Methods:Retrospective analysis was performed for clinical data of 45 LDLLS donors and recipients from June 2021 to September 2022.Traditional open donor liver resection (n=30) and robotic-assisted segmentectomy (n=15) were performed.Two groups were compared with regards to operative duration, intraoperative hemorrhage, postoperative healing and postoperative complications.SPSS 21.0 was utilized for statistical analysis.Independent sample T, paired sample T, Wilcoxon rank sum and Chi-square tests were performed for examining the inter-group differences.Results:Operative duration of robot-assisted surgery group was substantially longer than that of traditional open surgery group ( P<0.001). Intraoperative blood loss was less in robot-assisted surgery group was less than that in traditional open surgery group[(106.0±39.8) vs.(251.0±144.8) ml, P=0.001]. Postoperative hospital stay of robot-assisted surgery group was shorter than that of traditional open surgery group[6.0(6.0, 6.0) vs.7.0(6.0, 9.0), P<0.05]. Two cases of postoperative biliary leakage were observed in donor of traditional open surgery group.Among 2 cases of abdominal infection, one was due to biliary leakage from liver section and secondary surgery was then performed.One case of incisional infection and another case of thrombosis occurred in donor of traditional open surgery group.In robot-assisted surgery group, only one donor had amylase elevation.In traditional open surgery group, there were one case of local thrombosis in middle hepatic vein and one case of bile duct stricture.No long-term complications occurred in robot-assisted surgery group during a follow-up period of over 6 months.Finally recipient data analysis indicated that no significant inter-group differences existed in operative duration, intraoperative blood loss, postoperative hospital stay or postoperative abdominal infection ( P=0.634, P=0.180, P=0.86 and P=0.153). Conclusions:Robotic-assisted LDLLS proves to be be a safe and reliable option for living donor segmentectomy.It is superior to conventional LDLLS in terms of shorter hospital stay, less intraoperative blood loss and fewer postoperative complications.
3.Clinical features of Chinese patients with Takotsubo syndrome.
Zheng Feng LU ; Tao Juan CHONG ; Jian CHEN ; Wei WU ; Kan LIU
Chinese Journal of Cardiology 2022;50(4):375-385
Objective: To analyze the characteristics, diagnosis and treatment status of Takotsubo syndrome (TTS) of Chinese patients. Methods: Complete literature review was performed to summarize Chinese TTS cases between 2007 and 2018. Results: A total of 131 literatures were included including 160 TTS patients (age (58.3±14.7) years). There were 137 female patients (85.6%) in this cohort, the age was (59.6±14.0) years. There were 124 cases (77.5%) of stress-evoking factors, of which 83 cases (66.9%) were self-stress factors. There were 97 cases (60.6%) complained of chest pain and 15 cases (9.4%) with syncope. Forty-eight cases (30.0%) presented with cardiogenic shock. CK-MB and cTnT/I increased in 109 cases (80.1%). There were 124 cases (77.5%) presented with ST segment elevation on electrocardiogram, which were common in lead V2-V5. Echocardiography results were available in 128 cases (80.0%), reduced left ventricular ejection fraction (<50%) was reported in 78 cases (73.6%). Coronary angiography was performed in 133 patients (83.1%), of which 126 patients (94.7%) had normal coronary arteries or single non-significant stenosis. One hundred and thirty-eight patients (87.3%) were apical type. The misdiagnosis rate on admission was 96.9% (155/160), of which 141 cases (88.1%) were misdiagnosed as acute myocardial infarction. Nitroglycerin was used in 36 patients (30.3%). Angiotensin converting enzyme inhibitor or angiotensin Ⅱ receptor antagonist were used in 38 patients (31.9%). β blockers were used in 46 patients (38.7 %). Dopamine was used in 22 cases (18.5%) and norepinephrine was used in 12 cases (10.1%). Intra-aortic balloon counter pulsation was used in 5 cases (3.1%). Cardiopulmonary resuscitation was performed in 9 cases (5.6%). Cardiac function recovery time was 7 (6, 15) days. The average InterTAK diagnosis score was (51.5±18.1) points, and value was>70 points in 2 cases (1.3%). There were 92 patients in the high-risk group, and there were 3 recurrent TTS cases. Five patients died. Conclusions: TTS incidence tends to be young and dominates in female in China. The misdiagnosis rate is extremely high on admission. Most patients are treated with medication.
Adult
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Aged
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Echocardiography
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Electrocardiography
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Female
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Humans
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Middle Aged
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Stroke Volume/physiology*
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Takotsubo Cardiomyopathy/diagnosis*
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Ventricular Function, Left/physiology*
4.Effect of Prolonged Storage of Packed Red Blood Cells on Recurrence-free and Overall Survivals after Curative Resection for Hepatocellular Carcinoma
Rui-feng XUE ; Chong-xi ZHAO ; Pei-zong WANG ; Dong-tai CHEN ; Xiao-hui CHEN ; Wei-an ZENG ; Qiang LI
Journal of Sun Yat-sen University(Medical Sciences) 2022;43(3):449-461
ObjectiveProlonged storage of packed red blood cells (PRBC) is reportedly associated with poor clinical outcomes in critically ill, trauma, and cardiac surgery patients. However, the impact of PRBC’s age on long-term oncological outcomes in cancer patients remains poorly defined. Here we retrospectively evaluated the effect of PRBC’s age on overall survival and biochemical recurrence in patients undergoing curative resection of hepatocellular carcinoma. MethodsA total of 1 221 qualified patients undergoing curative hepatectomy for HCC between August 1, 2008 and June 30, 2012 at the Sun Yat-sen University Cancer Center (Guangzhou, PR China) were divided into nontransfused or transfused group. Transfused patients were further divided according to PRBC storage duration (fresh PRBC group, ≤ 14 days; old PRBC group, > 14 days). Overall survival (OS), intrahepatic recurrence-free survival (IRFS), extrahepatic metastasis-free survival (EMFS) were assessed and multivariate analyses were performed to evaluate the association of PRBC storage duration with cancer outcomes. ResultsA total of 251 (20.6%) patients received intraoperative PRBC transfusion. Of these, 112 and 125 patients were grouped in the fresh and the old PRBC groups, respectively. The Kaplan–Meier curves showed that both fresh PRBC group and old PRBC group had worse OS, IRFS, and EMFS than nontransfused group (P<0.001). Cox regression analyses further indicated that old PRBC transfusion was an independent prognostic factor of OS (HR=1.417, P=0.049), IRFS (HR=1.519, P=0.013) for patients with HCC; conversely, new PRBC transfusion was not. ConclusionIn patients undergoing curative hepatectomy, intraoperative transfusions of PRBC that had been stored for more than 2 weeks is independently associated with a significantly increased risk of intrahepatic recurrence and reduced overall survival.
5.Gene Mutation and Overexpression of Newly Diagnosed Multiple Myeloma Patients.
Yi FAN ; Shu-Juan WANG ; Yan-Fang LIU ; Chong WANG ; Ya-Fei LI ; Wei-Qiong WANG ; Qian-Qian HAO ; Dan-Feng ZHANG ; Ying-Mei LI ; Hui SUN ; Rong GUO ; Shao-Qian CHEN ; Xin-Sheng XIE ; Tao LI ; Ding-Ming WAN ; Zhong-Xing JIANG
Journal of Experimental Hematology 2022;30(1):166-169
OBJECTIVE:
To analyze the characteristics of gene mutation and overexpression in newly diagnosed multiple myeloma (NDMM) patients.
METHODS:
Bone marrow cells from 208 NDMM patients were collected and analyzed. The gene mutation of 28 genes and overexpression of 6 genes was detected by DNA sequencing. Chromosome structure abnormalities were detected by fluorescence in situ hybridization (FISH).
RESULTS:
Gene mutations were detected in 61 (29.33%) NDMM patients. Some mutations occurred in 5 or more cases, such as NRAS, PRDM1, FAM46C, MYC, CCND1, LTB, DIS3, KRAS, and CRBN. Overexpression of six genes (CCND1, CCND3, BCL-2, CCND2, FGFR3, and MYC) were detected in 83 (39.9%) patients, and cell cycle regulation gene was the most common. Single nucleotide polymorphisms (SNP) changes were detected in 169 (81.25%) patients, the TP53 P72R gene SNP (70.17%) was the most common. Abnormality in chromosome structure was correlated to gene overexpression. Compared to the patients with normal chromosome structure, patients with 14q32 deletion showed higher proportion of CCND1 overexpression. Similarly, patients with 13q14 deletion showed higher proportion of FGFR3 overexpression, whereas patients with 1q21 amplification showed higher proportion of CCND2, BCL-2 and FGFR3 overexpression.
CONCLUSION
There are multiple gene mutations and overexpression in NDMM. However, there is no dominated single mutation or overexpression of genes. The most common gene mutations are those in the RAS/MAPK pathway and the genes of cyclin family CCND are overexpression.
Chromosome Aberrations
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Humans
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In Situ Hybridization, Fluorescence
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Multiple Myeloma/genetics*
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Mutation
6.Design and mechanical properties of biodegradable polymeric stent.
Yu CHEN ; Guanshi WANG ; Chong CHEN ; Anqiang SUN ; Wentao FENG ; Wentao JIANG
Journal of Biomedical Engineering 2020;37(6):967-973
Biodegradable stents (BDSs) are the milestone in percutaneous coronary intervention(PCI). Biodegradable polymeric stents have received widespread attention due to their good biocompatibility, moderate degradation rate and degradation products without toxicity or side effects. However, due to the defects in mechanical properties of polymer materials, the clinical application of polymeric BDS has been affected. In this paper, the BDS geometric configuration design was analyzed to improve the radial strength, flexibility and reduce the shrinkage rate of biodegradable polymeric stents. And from the aspects of numerical simulation, in vitro experiment and animal experiment, the configuration design and mechanical properties of biodegradable polymeric stents were introduced in detail in order to provide further references for the development of biodegradable polymeric stents.
Absorbable Implants
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Animals
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Percutaneous Coronary Intervention
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Polymers
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Prosthesis Design
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Stents
7.Detection of Asymptomatic Carotid Artery Stenosis in High-Risk Individuals of Stroke Using a Machine-Learning Algorithm.
Jun Xiong YIN ; Cheng YU ; Li Xia WEI ; Chuan Yong YU ; Hong Xing LIU ; Ming Yang DU ; Feng SUN ; Chong Jun WANG ; Xiao Shan WANG
Chinese Medical Sciences Journal 2020;35(4):297-305
Objective Asymptomatic carotid stenosis (ACS) is closely associated to the incidence of severe cerebrovascular diseases. Early identifying the individuals with ACS and its associated risk factors could be beneficial for primary prevention of stroke. This study aimed to investigate a machine-learning algorithm for the detection of ACS among high-risk population of stroke based on the associated risk factors.Methods A novel model of machine learning was utilized to screen the associated predictors of ACS based on 30 potential risk factors. The algorithm of this model adopted a random forest pattern based on the training data and then was verified using the testing data. All of the original data were retrieved from the China National Stroke Screening and Prevention Project (CNSSPP), including demographic, clinical and laboratory characteristics. The individuals with high risk of stroke were enrolled and randomly divided into a training group and a testing group at a ratio of 4:1. The identification of carotid stenosis by carotid artery duplex scans was set as the golden standard. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) was used to evaluate the efficacy of the model in detecting ACS.Results Of 2841 high risk individual of stroke enrolled, 326 (11.6%) were diagnosed as ACS by ultrasonography. The top five risk factors contributing to ACS in this model were identified as family history of dyslipidemia, high level of low-density lipoprotein cholesterol (LDL-c), low level of high-density lipoprotein cholesterol (HDL-c), aging, and low body mass index (BMI). Their weights were 11.8%, 7.6%, 7.1%, 6.1%, and 6.1%, respectively. The total weight of the top 15 risk factors was 85.5%. The AUC values of the model for detecting ACS with training dataset and testing dataset were 0.927 and 0.888, respectively.Conclusions This study demonstrated that the machine-learning algorithm could be used to identify the risk factors for ACS among high risk population of stroke. Family history of dyslipidemia may be the most important risk factor for ACS. This model could be a suitable tool to optimize the clinical approach for the primary prevention of stroke.
8.Sleep Status of Patients with Chronic Hepatitis B Virus Infection
Xiao-yan ZHENG ; Ming-xue YU ; Yu-sheng JIE ; Jing CAO ; Liu-ping SHA ; Yu-tian CHONG ; Yu-feng ZHANG ; Ji-hui2 WANG
Journal of Sun Yat-sen University(Medical Sciences) 2020;41(1):95-102
【Objective】To investigate the sleep status of patients with chronic HBV infection【Methods】From January 2019 to June 2019 ,353 patients with chronic hepatitis B virus infection in the outpatient department of the Third Affiliated Hospital of Sun Yat-sen University,using the sleepiness scale,insomnia scale,sleep quality scale,anxiety self- rating form and depression self- evaluation ,patients were scored and grouped according to sleep grading criteria. Patients were collected for gender,age,disease diagnosis,antiviral therapy,and educational level. Chi-square correlation test and multivariate logistic regression were applied to analyze the influencing factors of sleep. 【Results】 The overall sleepiness rate was 47.88%. The overall insomnia rate was 53.26%. There were 6.8% patients who had poor sleep quality. The risk factor of lethargy was the degree of anxiety(P = 0.000,OR = 3.076,95% CI 1.706~5.545). The risk factor of insomnia was anxiety(P = 0.000,OR = 14.693,95% CI 5.046~42.782)and depression(P = 0.002,OR = 2.279,95% CI1.340~3.877). The risk factor of sleep quality was anxiety(P = 0.000,OR = 9.990,95% CI 4.031~24.758).【Conclusions】
Patients with chronic HBV infection have a high proportion of subjective sleep disorders. The main influencing factor is mental state of the patient. A full understanding of the patients′ sleep status will help the patients′ treatment.
9.Effects of different transdermal penetration enhancers applied to herbal cake-partitioned moxibustion on liver lipids, HSL and HMG-CoA reductase in hyperlipidemia rabbits
Zong-Li LIAO ; Chong-Zheng ZHU ; Jing TAN ; Feng-Jiao LUO ; Lu SUN ; Wen-Tao HUANG ; Yan-Ping CHEN ; Ren-Da YANG ; Xiao-Rong CHANG
Journal of Acupuncture and Tuina Science 2020;18(3):157-164
Objective: To observe the effects of laurocapram and borneol as transdermal penetration enhancers applied to herbal cake-partitioned moxibustion on liver lipids, hormone-sensitive lipase (HSL) and hydroxymethylglutaryl CoA (HMG-CoA) reductase in hyperlipidemia rabbits.Methods: Forty New-Zealand rabbits were randomly divided into 5 groups using the random number table method, with 8 rats in each group. Rabbits in the blank group were fed routinely with a normal diet; rabbits in the other groups were fed with high-fat diet for 12 weeks to establish the hyperlipidemia model. Rabbits in the blank and the model groups were not given any intervention. After the model was prepared successfully, rabbits in the non-transdermal penetration enhancer group received herbal cake-partitioned moxibustion without transdermal penetration enhancers; rabbits in the laurocapram group and the borneol group received herbal cake-partitioned moxibustion with laurocapram or borneol respectively. After 4 weeks of treatment, the serum was isolated and enzyme-linked immunosorbent assay (ELISA) was applied for the detection of HSL and HMG-CoA reductase. The liver tissues were isolated, and total cholesterol (TC) and triglycerides (TG) were measured by enzymatic methods. One-step method was applied for high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) detection, and transmission turbidimetry was for apolipoprotein A1 (Apo-A1) and apolipoprotein B (Apo-B) detection. Results: The serum concentrations of the drugs in the laurocapram and the borneol groups were significantly higher than those in the non-transdermal penetration enhancer group (both P<0.05); all drug penetrations in the borneol group were significantly higher than those in the laurocapram group (both P<0.05), except for tanshinone ⅡA. Compared with the non-transdermal penetration enhancer group, the HSL was significantly increased while the HMG-CoA reductase was significantly decreased in the laurocapram and the borneol groups (both P<0.05); between groups, the HSL in the borneol group was significantly higher than that in the laurocapram group (P<0.05). Compared with the blank group, the levels of LDL-C, TG, TC and Apo-B in rabbit liver were significantly increased in the model group (P<0.05); compared with the model group, the levels of LDL-C, TG, TC and Apo-B in the non-transdermal penetration enhancer, the laurocapram, and the borneol groups were significantly decreased (all P<0.05); between groups, the TG and TC in the laurocapram group and the LDL-C, TG, TC and Apo-B in the borneol group were significantly lower than those in the non-transdermal penetration enhancer group (all P<0.05), and the TG, LDL-C and Apo-B in the borneol group were significantly lower than those in the laurocapram group (all P<0.05). Compared with the blank group, the HDL-C and Apo-A1 were significantly decreased in the model group (both P<0.05), while compared with the model group, the HDL-C and Apo-A1 were significantly increased in the non-transdermal penetration enhancer, the laurocapram, and the borneol groups (all P<0.05). Between groups, the Apo-A1 in the laurocapram group, the HDL-C and Apo-A1 in the borneol group were significantly higher than those in the non-transdermal penetration enhancer group (all P<0.05).Conclusion: The application of laurocapram and borneol, as transdermal penetration enhancers, in herbal cake-partitioned moxibustion can promote the penetration of the drugs in the herbal cake, increase the levels of HDL-C and Apo-A1, improve the metabolism of HSL and HMG-CoA reductase, and also simultaneously reduce the levels of TC, TG, LDL-C and Apo-B in the liver. The transdermal penetration enhancement effect of borneol is slightly better than or equivalent to that of laurocapram.
10.Transmission electron microscopic observation on gonad of Oncomelania hupensis offspring bred in Weishan Lake areas
Feng MIAO ; Zhong-Dao WU ; Jin-Lang WU ; Shi-Jun SHI ; Xin ZENG ; Jing WANG ; Hao-Yun YAN ; Chong-Xing ZHANG ; Xin LIU
Chinese Journal of Schistosomiasis Control 2020;32(2):195-197
Objective To observe the morphological changes in the testes and ovaries of adult 12th-generation Oncomelania hupensis bred for 12 winters in Weishan Lake areas. Methods The offspring of the adult O. hupensis snails bred in the Weishan Lake that were originated from the Yangzhou section of the Yangtze River was defined as the experiment group, while uninfected, adult O. hupensis snails captured from the marshland of the Yangzhou section of the Yangtze River served as the control group. Snails were dissected and intact testicular and ovarian specimens were sampled, routinely fixed, dehydrated, embedded, polymerized in an oven and sliced on an ultramicrotome. The sections were visualized under a transmission electron microscope, and the ultrastructure of the snail gonad was compared between the experiment and control groups. Results Transmission electron microscopy showed “9 + 2” microtubules on the transverse sections of the tails of sperm cells in the testes of male snails in the control group, with triangular acrosomes and spiral, dense nuclei seen in the tip, while in the experiment group, the “9 + 2” microtubules disappeared on the transverse sections of the tails of sperm cells in the testes of male snails, with low chromatin density found in the tip. Transmission electron microscopy revealed clear nucleolus and nuclear membranes in the ova of female snail ovaries, and displayed yolk body, liposomes and endoplasmic reticulum in the cytoplasm, bilayer twists of nuclear membrane and a uniform nucleolus in the control group, while in the experiment group, smooth nuclear membrane and unclear nucleolus were observed in the ova of female snail ovaries, with few contents seen within cells. Conclusions Following breeding for 12 winters in the Weishan Lake, the 12th-generation O. hupensis snails fail to fully adapt to the natural environment in northern China, and the remarkable changes in the ultrastructure of the snail gonad may be a cause of gradual decline and even extinction of O. hupensis in the Weishan Lake areas.

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