1.Research Tackling Paradigm and Technological Layout Strategies Based on Erectile Dysfunction, A Clinical Dominant Disease of Traditional Chinese Medicine
Qi ZHAO ; Yun CHEN ; Baoxing LIU ; Xuejun SHANG ; Fei SUN ; Xiaozhi ZHAO ; Zhigang WU ; Chao SUN ; Peihai ZHANG ; Wanjun CHENG ; Xing ZHOU ; Zhan QIN ; Yufeng PAN ; Weiwei TAO ; Jianhuai CHEN ; Mei MO ; Xiaoxiao ZHANG ; Xing ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):291-299
To thoroughly implement the strategic deployment outlined in the Opinions of the Central Committee of the Communist Party of China and the State Council on Promoting the Inheritance and Innovative Development of Traditional Chinese Medicine regarding research on dominant diseases of traditional Chinese medicine and to uphold the development philosophy of equal emphasis on traditional Chinese medicine and western medicine,the China Association of Chinese Medicine has fully played a leading academic role by systematically organizing and conducting a series of academic youth salons on clinical dominant diseases of traditional Chinese medicine. On September 13,2024,the 36th Youth Salon on Clinical Dominant Diseases was successfully held in Nanjing,focusing on the advantages of traditional Chinese medicine and the integrative traditional Chinese medicine and western medicine in the diagnosis and treatment of erectile dysfunction (ED). The conference brought together leading experts from traditional Chinese medicine,western medicine,and interdisciplinary fields,facilitating in-depth multidisciplinary discussions that led to key consensus on optimizing traditional Chinese medicine treatment protocols for ED,researching and developing new drugs of traditional Chinese medicine,and advancing interdisciplinary development in traditional Chinese medicine. This salon systematically sorted out the clinical strengths and distinctive features of traditional Chinese medicine in the diagnosis and treatment of ED. Based on current research foundations and clinical needs,it identified key directions for future scientific layout and scientific research tackling: (1) Standardization of syndrome differentiation system of traditional Chinese medicine for ED. (2) Optimization and standardization of intervention methods of integrated traditional Chinese medicine and western medicine. (3) High-quality clinical research guided by evidence-based medicine. (4) In-depth analysis of the pharmacological mechanisms of traditional Chinese medicine in the treatment of ED. (5) Clinical translation and application promotion of new drugs of traditional Chinese medicine. (6) Interdisciplinary integration and innovation in traditional Chinese medicine. For each research direction,key focus areas,expected objectives,and clinical value were further refined,along with the establishment of a scientifically sound priority funding level evaluation system. Therefore,building on the series of salons on the ED-focused dominant diseases of traditional Chinese medicine,this paper provides standardized guidance for clinical practice of traditional Chinese medicine in ED management,effectively contributing to the high-quality development of traditional Chinese medicine. It serves as a valuable reference for national scientific and technological strategic layout, research and development decision-making in new drugs of traditional Chinese medicine,research topic planning,and clinical guideline formulation.
2.Application of artificial intelligence and automated scripts in3D printing brachytherapy
Wentai LI ; Jiandong ZHANG ; Zhihe WANG ; Xiaozhen QI ; Yan DING ; Baile ZHANG ; Wenjun MA ; Yao ZHAI ; Weiwei ZHOU ; Yanan SUN ; Xin ZHANG
Chinese Journal of Radiological Health 2025;34(3):419-425
Objective To explore the efficiency improvement in segmenting neural network with the application of Transformer + U-Net artificial intelligence (AI) and modeling with the application of Python scripts in three-dimensional (3D) printing brachytherapy. Methods A Transformer + U-Net AI neural network model was constructed, and Adam optimizer was used to ensure rapid gradient descent. Computed tomography or magnetic resonance imaging data of patients were standardized and processed as self-made data sets. The training set was used to train AI and the optimal result weight parameters were saved. The test set was used to evaluate the AI ability. Python programming language was used to write an automated script to obtain the output segmentation image and convert it to the STL file for import. The source applicator and needle could be automatically modeled. The time of automatic segmentation and modeling and the time of manual segmentation and modeling were entered by two people, and the difference was verified by paired t-test. Results Dice similarity coefficient (DSC), mean intersection over union (MIOU), and Hausdorff distance (HD95) were used for evaluation. DSC was
3.Impact of GM-CSF deficiency on the disease course and immune response in mice infected with Exophiala oligosperma
DONG Qi ; LU Jiejie ; WU Weiwei
China Tropical Medicine 2025;25(1):28-
Objective To investigate the role of granulocyte-macrophage colony-stimulating factor (GM-CSF) deficiency in the pathogenesis of Exophiala oligosperma (E. oligosperma) infection, a dematiaceous fungus, aiming to provide new insights and evidence for the treatment of dematiaceous fungal infections. Methods C57BL/6 wild-type (WT) mice and Csf2 gene knockout (KO) mice (C57BL/6 background) were selected. Using E. oligosperma isolated from patients with caspase recruitment domain-containing protein 9 (CARD9) gene deficiency, a murine subcutaneous infection model was established to simulate the human infection route. The natural progression of infection in the mice was observed for six weeks, with skin lesion tissues collected at appropriate time points for pathological analysis and monitoring immune responses. Results Both WT and Csf2 KO mice exhibited spontaneous pathogen clearance and gradual recovery of foot tissue appearance during the progression of infection, with a 100% survival rate at the end of observation. Compared to WT mice, Csf2 KO mice showed reduced footpad swelling at 1 and 2 weeks post-infection (t=4.674, t=5.961, P<0.01). Fungal clearance in Csf2 KO mice was delayed, with fungal colonies still detectable in lesion tissues at week 4, and Periodic Acid-Schiff (PAS)-positive fungal spores observed in histopathological sections. There was no significant difference found in macrophage infiltration between WT and Csf2 KO mice during the early stages of infection (1-2 weeks) (P>0.05), while neutrophil infiltration was significantly reduced in Csf2 KO mice at week 2 (t=3.287, P<0.01). In addition, Csf2 KO mice exhibited lower levels of IL-6 and IL-1β in foot lesion homogenates at week 1 (t=4.686, t=4.102, P<0.05). Conclusions This study demonstrated that GM-CSF deficiency delays pathogenic fungi clearance, prolongs the disease course and affects early inflammatory cytokine production as well as neutrophil infiltration during the early stages of fungal infections.
4.Construction and fermentation optimization of a hydroxyectoine-producing Escherichia coli strain.
Hairui TONG ; Hao ZHANG ; Weiwei HUANG ; Qi ZHANG ; Yibin QIU ; Sha LI
Chinese Journal of Biotechnology 2025;41(9):3448-3458
Hydroxyectoine, a vital compatible solute, is widely utilized in cosmetics, food, pharmaceutical industries, and biologics. However, the current microbial fermentation methods for hydroxyectoine production face challenges including insufficient precursor supply and low yields. Therefore, developing engineering microbial strains capable of efficiently synthesizing hydroxyectoine is of great significance. In this study, we first constructed a high-yield ectoine-producing strain ECT04 by multi-copy integration of the ectoine synthesis genes ectABC into the pseudogene loci of Escherichia coli MG1655(DE3), achieving an ectoine titer of 6.03 g/L. Subsequently, we employed plasmids with varying copy numbers to express ectD from Chromohalobacter salexigens to enable the conversion for hydroxyectoine production. We further investigated the effects of promoter, co-substrate ɑ-ketoglutarate, Fe2+ concentration, and dissolved oxygen on hydroxyectoine synthesis. Through fed-batch fermentation in a 7-L bioreactor, we significantly enhanced the hydroxyectoine production efficiency, attaining a final titer of 8.58 g/L and a productivity of 0.24 g/(L·h). This work successfully achieved the de novo synthesis of hydroxyectoine in E. coli, laying a foundation for the efficient bioproduction of this compound.
Escherichia coli/genetics*
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Fermentation
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Amino Acids, Diamino/biosynthesis*
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Bioreactors/microbiology*
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Metabolic Engineering/methods*
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Chromohalobacter/genetics*
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Plasmids/genetics*
5.Survival time and influencing factors analysis of clinically diagnosed sporadic Creutzfeldt-Jakob disease patients in China from 2020 to 2022
Weiwei ZHANG ; Donglin LIANG ; Donghua ZHOU ; Yuan WANG ; Kang XIAO ; Wei ZHOU ; Xiaoping DONG ; Qi SHI
Acta Universitatis Medicinalis Anhui 2024;59(10):1842-1848
Objective To investigate the survival time of patients diagnosed with sporadic Creutzfeldt-Jakob disease in China between 2020 and 2022 and explore the associated factors influencing survival.Methods A retrospective analysis was conducted on clinically diagnosed cases with complete information on sporadic Creutzfeldt-Jakob dis-ease diagnosed by the China Creutzfeldt-Jakob disease surveillance network from 2020 to 2022,baseline information of patients was obtained from the case files,telephone follow-up was used to obtain the treatment and survival status of the patients after the diagnosis,life-table method was used for estimating the survival rate,Kaplan-Meier method was used for calculating the median survival time and the 95%CI,Cox regression model was used for univariate and multivariate analyses were used to screen for factors influencing survival time.Results The median survival time of the 300 patients was 5 months(95%CI:4.165-5.835).Univariate analysis revealed that factors such as age at onset,regional distribution,presence of corticobasal or extrapyramidal symptoms as initial manifestations,number of initial symptoms,presence of corticobasal or extrapyramidal functional abnormalities,number of major clinical manifestations,presence of typical electroencephalogram findings,and use of nasal feeding during the course of the disease were potential factors influencing survival time(P<0.1).Multivariate analysis showed that the risk of death in patients with onset age>65 years was 1.350 times higher than in patients with onset age ≤65 years(P=0.021,95.0%CI:1.046-1.742).Patients without pyramidal or extrapyramidal dysfunction had a 0.674-fold lower risk of death compared to those with these symptoms(P=0.020,95.0%CI:0.483-0.939).Patients who did not receive nasal feeding had a 1.817-fold higher risk of death compared to those who did(P<0.001,95.0%CI:1.406-2.349).Conclusion Age at onset,the presence of pyramidal or extrapyramidal functional abnormalities,and the use of nasal feeding during the disease course are factors influencing the survival time of pa-tients clinically diagnosed with sCJD.
6.Effect of Gualou Xiebai Banxiatang on Myocardial Microangiogenesis and HIF-1α/VEGF-related Pathways in Myocardial Ischemia Model Rats
Wenhao CHEN ; Weishan MENG ; Hong LI ; Weiwei TIAN ; Qi ZHANG ; Yingying TAN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(17):1-9
ObjectiveTo investigate the effect of Gualou Xiebai Banxiatang on cardiac function and myocardial histopathological changes in rats with ischemic myocardial injury, and to observe the effect of myocardial microvascular density (MVD), phosphatidylinositol 3-kinase (PI3K), mammalian target of rapamycin (mTOR), hypoxia-inducible factor-1 alpha (HIF-1α), and vascular endothelial growth factor (VEGF) signaling pathways on myocardial microangiogenesis. MethodSeventy male SD rats were randomly selected, with six rats in the normal group. The remaining rats were fed a high-fat diet and injected with isoproterenol hydrochloride (ISO,80 mg·kg-1·d-1, 2 d) to induce a hyperlipidemia-based ischemic heart disease model. After successful modeling, the rats were randomly divided into the model group, high, medium, and low dose groups of Gualou Xiebai Banxiatang, and the metoprolol group. The high, medium, and low dose groups of Gualou Xiebai Banxiatang were given Gualou Xiebai Banxiatang at 10.42, 5.21, 2.61 g·kg-1·d-1, respectively, while the metoprolol group was given metoprolol at 2.6 mg·kg-1·d-1. Both the normal and model groups were given an equivalent volume of physiological saline for 28 days. After the intervention, relevant tests were conducted, and serum was collected to measure heart function-related indicators. Hematoxylin-eosin (HE) and Masson staining were performed on ventricular tissue to observe pathological changes under a light microscope. Immunohistochemistry (IHC) was used to detect the positive expression of platelet endothelial cell adhesion molecule (CD31). Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression of N-terminal pro-brain natriuretic peptide (NT-proBNP) and VEGF. Western blot was used to detect the protein expression levels of PI3K/mTOR/HIF-1α/VEGF. ResultCompared with the normal group, the model group showed significantly increased serum levels of LDH, CK, CK-MB, NT-proBNP, and VEGF (P<0.01), significantly increased collagen volume fraction (CVF) (P<0.01), significantly decreased MVD (P<0.01), and elevated protein expression levels of PI3K, mTOR, HIF-1α, and VEGF (P<0.05, P<0.01). Compared with the model group, the metoprolol group had significantly lower serum levels of LDH, CK, CK-MB, and NT-proBNP (P<0.01), significantly higher VEGF levels (P<0.01), significantly decreased CVF (P<0.01), significantly increased MVD (P<0.01), and significantly increased protein expression levels of PI3K, mTOR, and VEGF (P<0.01), with no statistically significant change in HIF-1α protein expression. Compared with the model group, the high and medium dose groups of Gualou Xiebai Banxiatang had decreased serum levels of LDH, CK, CK-MB, and NT-proBNP (P<0.05, P<0.01), increased VEGF levels (P<0.05, P<0.01), significantly reduced CVF (P<0.01), increased MVD (P<0.05, P<0.01), and significantly increased protein levels of PI3K, mTOR, HIF-1α, and VEGF (P<0.01). In the low dose group of Gualou Xiebai Banxiatang, compared with the model group, serum levels of LDH and NT-proBNP were decreased (P<0.05), VEGF was increased (P<0.05). Moreover, CVF was decreased (P<0.05), and the protein expression levels of PI3K, mTOR, HIF-1α, and VEGF were significantly increased (P<0.01). ConclusionGualou Xiebai Banxiatang can improve cardiac function, reduce myocardial pathological damage, enhance endothelial cell function, promote myocardial microvascular formation, and upregulate the expression of PI3K, mTOR, HIF-1α, and VEGF proteins in myocardial tissue in rats with ischemic myocardial injury.
7.Analysis on the assessment value of DCE-MRI quantitative parameters and tumor markers for the curative effect of neoadjuvant chemotherapy for breast cancer
Rui MA ; Yanhui WANG ; Min DU ; Xianlong QI ; Lin ZHANG ; Weiwei WANG
China Medical Equipment 2024;21(1):73-77
Objective:To explore the assessment value of quantitative parameters of dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)and tumor markers in assessing the curative effect of neoadjuvant chemotherapy for breast cancer.Methods:A total of 75 patients with breast cancer who received neoadjuvant chemotherapy combined with surgical intervention in Jining No.1 People's Hospital from May 2019 to May 2022 were selected,and they were divided into effective group(54 cases)and ineffective group(21 cases)according to the Response Evaluation Criteria In Solid Tumour(RECIST).The Ve,Kep and Ktrans of DCE-MRI quantitative parameters and CEA,CA125 and CA15-3 levels of tumor markers between two groups were compared before and after chemotherapy,and the receiver operating characteristics(ROC)curve was adopted to analyze the predictive efficiency of each diagnostic method.Results:After chemotherapy,the differences of the Ve,Kep and Ktrans of quantitative parameters between the two groups were significant(t=7.237,51.695,16.879,P<0.05),respectively.The differences of the CEA,CA125 and CA15-3 of tumor markers between two groups were significant(t=44.201,6.736,6.885,P<0.05),respectively.The AUC value of combined prediction of 6 indicators included Ve,Kep,Ktrans,CEA,CA125 and CA15-3 was 0.979 in predicting the curative effect of neoadjuvant chemotherapy for breast cancer,which was significantly higher than the AUC value of each alone indicator,and the differences of them were statistically significant(Z=2.993,2.679,2.510,2.731,3.215,3.071,P<0.05),respectively.Conclusion:The combination of tumor markers and DCE-MRI quantitative parameters can better predict the curative effect of neoadjuvant chemotherapy for breast cancer,which can indirectly assess the prognosis.
8.Application value of optical surface monitoring system volume rendering technique body surface imaging in intensity-modulated radiotherapy for thoracic tumors
Zhiping XIAO ; Dingyu LI ; Xiugen FU ; Junchao LI ; Qi LIU ; Weiwei ZHONG
Cancer Research and Clinic 2024;36(1):47-51
Objective:To explore the application value of optical surface monitoring system (OSMS) volume rendering technique (VRT) body surface imaging in intensity-modulated radiotherapy for thoracic tumors.Methods:A retrospective case series study was performed. The clinical data of 65 patients with thoracic tumors treated with intensity-modulated radiotherapy at Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from September 2021 to October 2022 were retrospectively analyzed. In the first treatment,after cone-beam computed tomography (CBCT) scan and correction, VRT body surface images were obtained by using OSMS. In subsequent treatment, the VRT image was used as the benchmark and the 6-dimensional bed was automatically positioned to record the 6-dimensional bed positioning value. The CBCT scan was performed to record the translation and rotation errors of left-right direction (X-axis), head-foot direction (Y-axis) and front-rear direction (Z-axis). After the calibration of the 6-dimensional automatic bed shifting, the new real-time deltas (RTD) value of digital imaging and communications in medicine (DICOM) body surface image was recorded, and the new VRT image was obtained. CBCT registration error value was defined as VRT image-guided setup error. The sum of CBCT registration error value and moving bed movement value was defined as the body surface marker line-guided setup error. The sum of CBCT registration error value and the recorded DICOM image RTD value was defined as the theoretical error of DICOM image-guided setup. The advantages and disadvantages of VRT image, body surface marker line and DICOM image-guided setup were compared and analyzed.Results:There were 42 males and 23 females in 65 patients with thoracic tumors, and the age [ M ( Q1, Q3)] was 58 years (51 years, 64 years). The linear errors [ M ( Q1, Q3)] of VRT image-guided setup in X, Y and Z axes were 0.6 mm (0.3 mm, 1.2 mm), 1.2 mm (0.5 mm, 2.4 mm) and 1.1 mm (0.5 mm, 1.9 mm); and the rotational errors were 0.4° (0.1°, 0.7°), 0.4° (0.1°, 0.6°) and 0.4° (0.2°, 0.6°). The linear errors of the marker line-guided setup were 1.6 mm (0.9 mm, 2.6 mm), 2.2 mm (1.1 mm, 3.8 mm) and 1.0 mm (0.4 mm, 1.8 mm); and the rotational errors were 0.7° (0.3°, 1.2°), 0.5° (0.2°, 0.8°) and 0.5° (0.2°, 0.8°). The linear errors of the DICOM image-guided positioning were 1.1 mm (0.6 mm, 1.9 mm), 2.1 mm (1.0 mm, 3.4 mm) and 1.3 mm (0.6 mm, 3.1 mm), and the rotational errors were 0.6° (0.2°, 1.1°), 0.7° (0.3°, 1.1°), 0.7° (0.2°, 1.1°). Compared with the marker line-guided setup, except for Z-axis linear error ( P = 0.218), the VRT-guided setup errors were low (all P < 0.001). Compared with the DICOM imaging-guided setup, the VRT image-guided setup linear error and rotational error in X-, Y- and Z-axis were low (all P < 0.01). Conclusions:VRT image-guided setup is superior to traditional body surface marker setup and DICOM imaging setup; OSMS VRT body surface imaging can effectively improve the setup accuracy and stability of intensity-modulated radiotherapy for thoracic tumors, and reduce the setup errors.
9.Trends in the distribution of Oncomelania hupensis in forestlands in Songjiang District, Shanghai Municipality from 2009 to 2023
Qi MAO ; Caiying SUN ; Anqi LI ; Weiwei LU ; Xihong LÜ ; Xuehui LU ; Yanjun JIN ; Qing YU
Chinese Journal of Schistosomiasis Control 2024;36(2):165-168
Objective To investigate the changes in distribution of Oncomelania hupensis snails in forestlands in Songjiang District, Shanghai Municipality from 2009 to 2023, so as to provide insights into formulation of O. hupensis snail surveillance programs. Methods The reports on O. hupensis snail surveillance in Songjiang District, Shanghai Municipality from 2009 to 2023 were collected, and the snail surveillance data in forestlands were extracted. The trends in the proportion of areas with snails in forestlands in total areas with snails, occurrence of frames with living snails and density of living snails were evaluated using a Joinpoint regression model in Songjiang District from 2009 to 2023, and the annual percent change (APC) and average annual percent change (AAPC). Results A total of 40 sites with snails were found in forestlands in 14 administrative villages of 4 townships, Songjiang District, Shanghai Municipality from 2009 to 2023. A total of 39 065 frames were surveyed for snails in settings covering an area of 609 600 m2, and there were 6 084 frames with snails, covering 151 250 m2 snail habitats. A total of 22 210 snails were captured, with the highest density of 260.00 snails/0.1 m2, and 6 262 snails were dissected, with no Schistosoma japonicum infection identified in snails. The proportion of areas with snails in forestlands in total areas with snails appeared a tendency towards a rise in forestlands in Songjiang District, Shanghai Municipality from 2009 to 2023 (APC = AAPC = 24.9%, P > 0.05); however, there were no turning points in the trend curve, with the highest proportion seen in 2009 (53.81%), the lowest in 2011 and 2023 (both 0) and a mean proportion of 24.81%. The occurrence of frames with living snails appeared a tendency towards a rise from 2009 to 2023 (APC = AAPC = 41.5%, P > 0.05); however, there were no turning points in the trend curve, with the highest occurrence in 2009 (53.81%), the lowest in 2011 and 2013 (both 0), and the mean occurrence of 15.57%. In addition, the density of living snails appeared a tendency towards a rise from 2009 to 2023 (APC = AAPC = 55.0%, P > 0.05); however, there were no turning points in the trend curve, with the highest density in 2023 (0.96 snails/0.1 m2), the lowest in 2011 and 2013 (both 0), and a mean density of 0.57 snails/0.1 m2. Conclusions The difficulty in O. hupensis snail control and risk of imported snails appeared a tendency towards a rise in forestlands in Songjiang District, Shanghai Municipality over years from 2009 to 2023. Supervision and assessment prior to seedling transplantation and intensified surveillance post-transplantation are recommended to reduce the risk of O. hupensis snail importation and spread.
10.Surveillance and trend analysis of snails in Songjiang District of Shanghai from 2007 to 2023
Qi MAO ; Caiying SUN ; Anqi LI ; Weiwei LU ; Xihong LYU ; Xuehui LU ; Yanjun JIN ; Qing YU
Shanghai Journal of Preventive Medicine 2024;36(5):444-447
ObjectiveTo analyze the monitoring results and trends of Oncomelania in Songjiang District of Shanghai from 2007 to 2023, and to provide reference for future monitoring work. MethodsThe data of snail monitoring in Songjiang District from 2007 to 2023 were collected, including the location of snail spots, the number of survey frames, the area with snails, the number of frames with snails, the total number of snails, etc. The density of living snails and the occurrence rate of living snail frames were calculated. ResultsFrom 2007 to 2023, a total of 158 snail spots were found in 22 administrative villages in 4 towns in Songjiang District, including 131 emerging snail habitats (82.91%) and 27 reemerging snail habitats (17.09%). The total snail area was 175 980 m2, the number of snail frames was 10 061, and 33 302 snails were captured. The highest density was 260/0.11 m2, and 15 662 snails were dissected. No positive snails were found. The average density of living snails was 0.60/0.11 m2 and the average occurrence rate of living snail frames was 17.99%. The snail areas in different areas were Yexie Town 126 000 m2 (71.60%), Maogang Town 26 470 m2 (15.04%), Xinbang Town 17 040 m2 (9.68%), and Shihudang Town 6 470 m2 (3.68%). The average density of living snails in different areas was 0.89/0.11 m2 in Yexie Town, 0.65/0.11 m2 in Maogang Town, 0.26/0.11 m2 in Shihudang Town and 0.24/0.11 m2 in Xinbang Town. The snail areas of different snail habitats were as follows: woodland 151 250 m2(85.95%), river 13 810 m2(7.85%), ditch 6 910 m2(3.93%), farmland 4 010 m2(2.28%). The average density of living snails in different snail habitats: ditch 1.01/0.11 m2, beach 0.86/0.11 m2, woodland 0.57/0.11 m2, river 0.40/0.11 m2. The occurrence rate of living snail frames in different regions and different snail environment types showed a downward trend and the difference was statistically significant. ConclusionAlthough the snail monitoring indicators such as snail area, average living snail density and average living snail frame occurrence rate in Songjiang District are still at its historically low level, the average living snail density and average living snail frame occurrence rate are still high compared with other regions or the national average. We should focus on the upper reaches and tributaries of the Huangpu River, especially the key areas of seedling transplantation, and strengthen monitoring and supervision to reduce the risk of snail input.


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