1.Clinical Efficacy of Tangning Tongluo Tablets for Nonproliferative Diabetic Retinopathy
Fuwen ZHANG ; Junguo DUAN ; Wen XIA ; Tiantian SUN ; Yuheng SHI ; Shicui MEI ; Xiangxia LUO ; Xing LI ; Yujie PAN ; Yong DENG ; Chuanlian RAN ; Hao CHEN ; Li PEI ; Shuyu YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):132-139
ObjectiveTo observe the clinical efficacy and safety of Tangning Tongluo tablets in the treatment of nonproliferative diabetic retinopathy (DR). MethodsFourteen research centers participated in this study, which spanned a time interval from September 2021 to May 2023. A total of 240 patients with nonproliferative DR were included and randomly assigned into an observation group (120 cases) and a control group (120 cases). The observation group was treated with Tangning Tongluo tablets, and the control group with calcium dobesilate capsules. Both groups were treated for 24 consecutive weeks. The vision, DR progression rate, retinal microhemangioma, hemorrhage area, exudation area, glycosylated hemoglobin (HbA1c) level, and TCM syndrome score were assessed before and after treatment, and the safety was observed. ResultsThe vision changed in both groups after treatment (P<0.05), and the observation group showed higher best corrected visual acuity (BCVA) than the control group (P<0.05). The DR progression was slow with similar rates in the two groups. The fundus hemorrhage area and exudation area did not change significantly after treatment in both groups, while the observation group outperformed the control group in reducing the fundus hemorrhage area and exudation area. There was no significant difference in the number of microhemangiomas between the two groups before treatment. After treatment, the number of microhemangiomas decreased in both the observation group (Z=-1.437, P<0.05) and the control group (Z=-2.238, P<0.05), and it showed no significant difference between the two groups. As the treatment time prolonged, the number of microhemangiomas gradually decreased in both groups. There was no significant difference in the HbA1c level between the two groups before treatment. After treatment, the decline in the HbA1c level showed no significant difference between the two groups. The TCM syndrome score did not have a statistically significant difference between the two groups before treatment. After treatment, neither the TCM syndrome score nor the response rate had significant difference between the two groups. With the extension of the treatment time, both groups showed amelioration of TCM syndrome compared with the baseline. ConclusionTangning Tongluo tablets are safe and effective in the treatment of nonproliferative DR, being capable of improving vision and reducing hemorrhage and exudation in the fundus.
2.Influence of Hedgehog signaling pathway activation on calvarial defect healing in type I diabetic mice
WU Yingzhang ; LIU Linan ; LIU Shibo ; HU Pei ; LUO En
Journal of Prevention and Treatment for Stomatological Diseases 2025;33(7):542-553
Objective:
This study aimed to elucidate the mechanisms underlying the impaired bone healing capacity in type 1 diabetes (T1DM) by investigating the role of the Hedgehog (Hh) signaling pathway in the impaired healing of cranial defects caused by T1DM.
Methods:
This study was approved by the experimental animal ethics committee of our hospital. A cranial defect model was established using Akita transgenic mice with spontaneous type I diabetes. The impact of T1DM on osteogenic differentiation and the Hh signaling pathway during cranial defect healing was explored by MicroCT scanning and immunohistochemical (IHC) analysis of osteocalcin (Ocn), Indian Hedgehog (Ihh), Patched1 (Ptch1), and zinc finger protein GLI1 (Gli1). Subsequently, the Hh signaling pathway was activated using smoothened agonist (SAG) (10 mg/kg, gavage), and its potential to improve cranial defect healing in T1DM was assessed by MicroCT and IHC staining. Finally, the ability of SAG (1 000 nmol/L) to counteract the inhibitory effects of a high-glucose environment (25 mol/L) on osteogenic differentiation of mouse bone marrow mesenchymal stem cells (BMSCs) was investigated through in vitro experiments. Detection methods included Alkaline Phosphatase and Alizarin Red staining, as well as quantitative real-time PCR (qPCR) analysis of the osteogenesis-related genes Alp, Spp1, Bglap, and Sp7.
Results:
Akita mice exhibited early, stable, and significant spontaneous T1DM characteristics. On postoperative day 21, the newly formed bone in the cranial defect area of Akita mice showed significant decreases in the bone volume-to-tissue volume ratio, volumetric bone mineral density, and Ocn expression (P < 0.05), with significant downregulation of Ihh, Ptch1, and Gli1 (P < 0.05). Activation of the Hh signaling pathway by SAG significantly mitigated the negative impact of T1DM on cranial defect healing in Akita mice (P < 0.05). Moreover, after SAG treatment, the inhibitory effects of the high-glucose environment on the alkaline phosphatase activity and in vitro mineralization capacity of BMSCs were significantly alleviated (P < 0.05), and the expression levels of osteogenic differentiation-related genes were significantly upregulated (P < 0.05).
Conclusion
T1DM inhibits cranial defect healing in Akita mice by suppressing the expression of the Hh signaling pathway, whereas activation of the Hh signaling pathway promotes osteogenesis and ameliorates the inhibitory effects of T1DM on bone healing.
3.Role of Ferroptosis in Bone Homeostasis and Traditional Chinese Medicine Intervention: A Review
Bo WEI ; Juan LI ; Yiwei JIANG ; Yuying ZHOU ; Chunhui LUO ; Zhongchao YU ; Pei LIU ; Yunxiang HAI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(3):249-257
Osteoporosis (OP) is a systemic metabolic bone disease characterized by bone microstructure degeneration and bone mass loss, which has a high prevalence and disability rate. Effective prevention and treatment of OP is a major difficulty in the medical community. The nature of OP is that multiple pathological factors lead to the imbalance of human bone homeostasis maintained by osteoblasts and osteoclasts. Ferroptosis is a non-apoptotic cell death pathway, and its fundamental cause is cell damage caused by iron accumulation and lipid peroxidation. Studies have shown that ferroptosis is involved in and affects the occurrence and development of OP, which leads to OP by mediating the imbalance of bone homeostasis. Ferroptosis is an adjustable form of programmed cell death. The intervention of ferroptosis can regulate the damage degree and death process of osteoblasts and osteoclasts, which is beneficial to maintain bone homeostasis, slow down the development process of OP, improve the clinical symptoms of patients, reduce the risk of disability, and improve their quality of life. However, there are few studies on ferroptosis in OP. Traditional Chinese medicine (TCM) is a medical treasure with unique characteristics and great application value in China. It has been widely used in China and has a long history. It has the multi-target and multi-pathway advantages in the treatment of OP, with high safety, few toxic and side effects, and low treatment cost, and has a significant effect in clinical application. The intervention of TCM in ferroptosis to regulate bone homeostasis may be a new direction for the prevention and treatment of OP in the future. This article summarized the regulatory mechanisms related to ferroptosis, discussed the role of ferroptosis in bone homeostasis, and reviewed the current status and progress of active ingredients in TCM compounds and monomers in the regulation of OP through ferroptosis, so as to provide a theoretical basis for the participation of TCM in the prevention and treatment of OP in the future.
4.Exploring Scientific Connotation of "Fried Charcoal Survivability" of Lonicerae Japonicae Flos Based on Color-composition Correlation
Ting ZOU ; Jing WANG ; Xu WU ; Kai YANG ; Ming DANG ; Xiuchu GUO ; Lin WANG ; Chenxi LUO ; Juan PEI ; Chongbo ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(4):175-182
ObjectiveTo explore the scientific connotation of fried charcoal survivability of Lonicerae Japonicae Flos(LJF) by analyzing the correlation between the color change and the intrinsic components during the processing of LJF Carbonisata(LJFC), and taking pH, charcoal adsorption and microscopic characteristics as indexes. MethodLJFC samples with different degrees of processing were prepared according to the stir-frying time of 0.0, 1.5, 3.0, 4.5, 6.0, 7.5, 9.0, 10.5 min(numbered S1-S8), and the contents of gallic acid, chlorogenic acid, cryptochlorogenic acid, rutin, luteoloside, isochlorogenic acid A and isochlorogenic acid C were determined by high performance liquid chromatography(HPLC), and the L*(brightness), a*(red-greenness) and b*(yellow-blueness) of LJFC samples with different degrees of processing were determined by spectrophotometer, and the correlation analysis and principal component analysis(PCA) between the contents of seven representative components and the color of the samples were carried out by SPSS 26. 0 and SIMCA-P 14.1. Then pH, adsorption force and characteristic structure of different samples of LJFC were detected and the processing pattern of LJFC was analyzed. ResultThe results of quantitative analysis revealed that the contents of luteoloside, rutin, chlorogenic acid and isochlorogenic acid A gradually decreased, and the contents of cryptochlorogenic acid, isochlorogenic acid C and gallic acid firstly increased and then decreased. The L* and b* of the sample powders decreased, and a* showed a trend of increasing and then decreasing. The L* and b* were positively correlated with the contents of chlorogenic acid, rutin, luteoloside, isochlorogenic acid A, b* was positively correlated with the content of gallic acid, and a* was positively correlated with the contents of cryptochlorogenic acid and isochlorogenic acid C. PCA revealed that samples could be clearly divided into 3 groups, S1-S2 as one group, S3-S5 as one group, and S6-S8 as one group, with S3 having the highest score. The results of regression analysis showed that only isochlorogenic acid C could be used to predict the contents of components by colorimetric values combined with regression equations. Physicochemical analysis showed that pH of LJFC increased with the increase of degree of charcoal stir-frying, while adsorption force showed a tendency of increasing and then decreasing, with the highest adsorption force in the S5 sample, and the non-glandular hairs, calcium oxalate clusters and pollen grains had a varying degree of decreasing with the deepening of processing degree, and the microstructures of S6-S8 samples were obviously charred with pollen grains almost invisible. ConclusionThe changes in chemical composition and color characteristics of LJFC during the processing have certain correlations, combined with the changes in physicochemical properties, S5 sample is found to be the optimal processed products, which can provide a reference for the processing standardization and quality evaluation of LJFC, and enrich the scientific connotation of fried charcoal survivability of LJF.
5.Study on the antifungal activity and mechanism of Huangqin decoction against Trichophyton mentagrophytes
Chengying SHEN ; Zhong LUO ; Pei ZHANG ; Fengyi DENG ; Baode SHEN ; Jianxin HU
China Pharmacy 2024;35(3):311-315
OBJECTIVE To study the antifungal activity of Huangqin decoction (HQD) against Trichophyton mentagrophytes and explore its mechanism. METHODS Minimal inhibitory concentration (MIC), minimal fungicidal concentration (MFC), mycelial length, spore germination rate, biomass and mycelium ultrastructure observation were performed to evaluate the antifungal activity of HQD against T. mentagrophytes. The effects of HQD on the cell wall of T. mentagrophytes were detected through sorbitol protection experiment. By measuring the content of ergosterol and the activities of squalene epoxide (SE) and lanosterol 14α-demethylase (CYP51), the activity of HQD on the cell membrane of T. mentagrophytes was investigated. The effects of HQD on T. mentagrophytes mitochondria were investigated by determining the activities of malate dehydrogenase (MDH), succinate dehydrogenase (SDH), and ATPases (including sodium potassium ATPase, calcium magnesium ATPase, and total ATPase). RESULTS HQD exhibited significant antifungal activity against T. mentagrophytes with MIC of 3.13 mg/mL and MFC of 25 mg/mL. After intervention with HQD, the mycelial length of T. mentagrophytes was significantly shortened (P<0.05); spore germination rate, biomass, the content of ergosterol in the cell membrane, the activities of SE and CYP51 in the cell membrane and MDH, SDH and ATPase in mitochondria were all decreased significantly (P<0.05); cell structure had been ;damaged to a certain extent, but the integrity of the cell wall had not been affected. CONCLUSIONS HQD shows significant antifungal activity against T. mentagrophytes, the mechanism of which may be associated with reducing the 0791- content of ergosterol in the cell membrane and the activities of SE, CYP51, and mitochondria-related enzymes.
6.The Role of Mechanical Sensitive Ion Channel Piezo in Digestive System Diseases
Si-Qi WANG ; Xiang-Yun YAN ; Yan-Qiu LI ; Fang-Li LUO ; Jun-Peng YAO ; Pei-Tao MA ; Yu-Jun HOU ; Hai-Yan QIN ; Yun-Zhou SHI ; Ying LI
Progress in Biochemistry and Biophysics 2024;51(8):1883-1894
The Piezo protein is a non-selective mechanosensitive cation channel that exhibits sensitivity to mechanical stimuli such as pressure and shear stress. It converts mechanical signals into bioelectric activity within cells, thus triggering specific biological responses. In the digestive system, Piezo protein plays a crucial role in maintaining normal physiological activities, including digestion, absorption, metabolic regulation, and immune modulation. However, dysregulation in Piezo protein expression may lead to the occurrence of several pathological conditions, including visceral hypersensitivity, impairment of intestinal mucosal barrier function, and immune inflammation.Therefore, conducting a comprehensive review of the physiological functions and pathological roles of Piezo protein in the digestive system is of paramount importance. In this review, we systematically summarize the structural and dynamic characteristics of Piezo protein, its expression patterns, and physiological functions in the digestive system. We particularly focus on elucidating the mechanisms of action of Piezo protein in digestive system tumor diseases, inflammatory diseases, fibrotic diseases, and functional disorders. Through the integration of the latest research findings, we have observed that Piezo protein plays a crucial role in the pathogenesis of various digestive system diseases. There exist intricate interactions between Piezo protein and multiple phenotypes of digestive system tumors such as proliferation, apoptosis, and metastasis. In inflammatory diseases, Piezo protein promotes intestinal immune responses and pancreatic trypsinogen activation, contributing to the development of ulcerative colitis, Crohn’s disease, and pancreatitis. Additionally, Piezo1, through pathways involving co-action with the TRPV4 ion channel, facilitates neutrophil recruitment and suppresses HIF-1α ubiquitination, thereby mediating organ fibrosis in organs like the liver and pancreas. Moreover, Piezo protein regulation by gut microbiota or factors like age and gender can result in increased or decreased visceral sensitivity, and alterations in intestinal mucosal barrier structure and permeability, which are closely associated with functional disorders like irritable bowel sydrome (IBS) and functional consitipaction (FC). A thorough exploration of Piezo protein as a potential therapeutic target in digestive system diseases can provide a scientific basis and theoretical support for future clinical diagnosis and treatment strategies.
7.Knowledge-attitude-practice survey and mechanism on AIDS/STDs among migrant workers in the main urban area of Chengdu city
Cuihua Zhang ; Jinglin Zhou ; Luling You ; Yuyan Wu ; Min Luo ; Rong Pei
Acta Universitatis Medicinalis Anhui 2024;59(11):2040-2046
Objective:
To analyze the current situation, influencing factors and mechanism of knowledge-attitude-practice(KAP) regarding acquired immune deficiency syndrome(AIDS)/sexually transmitted diseases(STDs) among migrant workers in Chengdu's main urban area, so as to provide a basis for the development of effective prevention and control policies for this group.
Methods:
Convenience sampling and systematic sampling were used to collect demographic information and data on knowledge, attitudes, and sexual behavior characteristics of AIDS/STDs of the participants. The collected data were organized and statistically analyzed by EpiData 3.1 and SPSS 26.0 software. Additionally, a KAP path analysis model was constructed by using AMOS 24.0 software.
Results:
A total of 257 valid questionnaires were obtained. The AIDS awareness rate was 55.6%, with a mean scores of(5.59±1.61). The awareness rate of STDs was 37.4%, with a mean scores of(9.05±3.00). Discrimination attitudes towards AIDS and STDs were reported by 58 participants(22.6%) and 44 participants(17.1%) respectively. The prevalence of high-risk sexual behavior was 3.50%. Men(OR=0.500, 95%CI: 0.279-0.897) acted as deterrents to knowledge of AIDS. On the other hand, childlessness facilitated discrimination against AIDS(OR=2.748, 95%CI: 1.385-5.451) and STDs(OR=2.287, 95%CI: 1.084-4.825). There was lower likelihood of engaging in high-risk sexual behavior among migrant workers in Chengdu's main urban area who were older(OR=0.854, 95%CI: 0.785-0.929). The occurrence of high-risk sexual behaviors was influenced both directly and indirectly by attitudes towards AIDS and related knowledge. There was a positive correlation between knowledge about AIDS and STDs and attitudes towards them(r=0.15,0.24, bothP<0.05), as well as between attitudes towards AIDS and attitudes towards STDs(r=0.57,P<0.05). That is, the higher the scores of knowledge, the less likely one was to hold discrimination attitudes. Therefore, increasing the rate of knowledge awareness could reduce discrimination towards AIDS/STDs and the occurrence of high-risk sexual behaviors.
Conclusion
The level of AIDS/STDs knowledge among the migrant workers in Chengdu′s main urban area is concerning. Innovative interventions should be intensified in key areas and populations.
8.Investigation Report of the Species and Reserves of Chinese Materia Medica Resources in Sichuan Based on the 4th Chinese Materia Medica Resource Inventory
Qingmao FANG ; Qingmiao LI ; Yi ZHOU ; Wentao ZHU ; Bing LUO ; Mei ZHANG ; Xianjian ZHOU ; Ping WU ; Ping HU ; Hongsu WANG ; Cheng PENG ; Jin PEI ; Yuecheng LI ; Hao ZHANG ; Cheng ZHUANG ; Youqing GAN ; Minghua LUO ; Junning ZHAO
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(8):1946-1958
Objective To compare the changes of the Chinese Materia Medica resources(CMMR)in Sichuan based on the data of the 3rd Chinese Materia Medica Resource Inventory(CMMRI,1983-1986)and the 4th CMMRI(2011-2022).Methods Using new techniques,after field investigation,collection and identification of the specimens of the animals,plants and minerals.The data of the CMMR in Sichuan found in the 4th CMMRI were analysed and compared with the data of 3rd CMMRI.Results ①9055 species of CMMR were found in Sichuan during the 4th CMMRI,including 8272 species of medicinal plants,745 species of medicinal animals and 38 species of medicinal minerals.Compared with the 3rd CMMRI,the number of CMMR found in Sichuan have greatly increased.The number of medicinal plants increased 5018 species,the number of medicinal animals increased 637 species and the number of medicinal minerals increased 5 species,too.②The medicinal plants is the main part of the CMMR,and the higher plants(7774 species)has the absolute advantage of the CMMR.The top 20 families which have plenty of plant species include Compositae,Rosaceae,Leguminosae,Ranunculaceae,etc.③ Based on the data of the CMMR of the 183 counties in Sichuan,the reserves of 235 species of wild CMMR in Sichuan is about 36.72 million ton.There were 49 CMMR which have reserves beyond 100 thousand tons,such as Arisaematis rhizoma,Epimedii folium,Cimicifugae rhizoma,Acori tatarinowii rhizoma,Gentianae macrophyllae radix,Polygoni multiflori radix etc.④In 2021,there were 215 species of CMMR cultivated in Sichuan,the main species were Aurantii fructus,Chuanxiong rhizoma,Polygonati rhizome,Salviae miltiorrhizae radix et rhizome.The planting area was 8.17 million and the production was 1.26 million ton.⑤All 183 countries were found CMMR,the number of the species of CMMR in 30 countries exceeded 800,including 16 countries which had more than 1000 kinds of CMMR,such as Emeishan,Hongya,Muli etc.The total types of the CMMR(up 118.31%),the reserves of the wild CMMR(up 119 times)and the number of the counties(up 3 times)which had plenty of CMMR,showed a marked increase over the 3rd CMMRI.8 new species were found in the the 4th CMMRI,such as Codonopsis atriplicifolia,Tongoloa tagongensis,Allium xinlongense,etc.Conclusion The species,the reserves of the CMMR and the resource rich countries in Sichuan are the top 3 in China and Sichuan is worthy of the title of"Hometown of Traditional Chinese Medicine".The compositions and types of the family,genus and species of the CMMR in Sichuan have significantly increased.The basic information of the CMR in Sichuan was clearly found out during the 4th CMMRI,and beneficial for the sustainable development and utilization of the CMMR in Sichuan.
9.The clinical significance of lateral pelvic sentinel lymph node biopsy using indocyanine green fluorescence navigation in laparoscopic lateral pelvic lymph node dissection
Hao SU ; Zheng XU ; Mandula BAO ; Shou LUO ; Jianwei LIANG ; Wei PEI ; Xu GUAN ; Zheng LIU ; Zheng JIANG ; Mingguang ZHANG ; Zhixun ZHAO ; Weisen JIN ; Haitao ZHOU
Chinese Journal of Oncology 2024;46(2):140-145
Objectives:This study aims to explore the clinical significance of lateral pelvic sentinel lymph node biopsy (SLNB) using indocyanine green (ICG) fluorescence navigation in laparoscopic lateral pelvic lymph node dissection (LLND) and evaluate the accuracy and feasibility of this technique to predict the status of lateral pelvic lymph nodes (LPLNs).Methods:The clinical and pathological characteristics, surgical outcomes, lymph node findings and perioperative complications of 16 rectal cancer patients who underwent SLNB using ICG fluorescence navigation in laparoscopic LLND in the Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College during April 2017 and October 2022 were retrospectively collected and analyzed. The patients did not receive preoperative neoadjuvant radiotherapy and presented with LPLNs but without LPLN enlargement (MRI showed the maximum short axes of the LPLNs were ≥5 mm and <10 mm at first visit).Results:All 16 patients were successfully performed SLNB using ICG fluorescence navigation in laparoscopic LLND. Three patients underwent bilateral LLND and 13 patients underwent unilateral LLND. The lateral pelvic sentinel lymph nodes (SLNs) were clearly fluorescent before dissection in 14 patients and the detection rate of SLNs for these patients was 87.5%. Lateral pelvic SLN metastasis was diagnosed in 2 patients and negative results were found in 12 patients by frozen pathological examinations. Among the 14 patients in whom lateral pelvic SLNs were detected, the dissected lateral pelvic non-SLNs were all negative. All dissected LPLNs were negative in two patients without fluorescent lateral pelvic SLNs. The specificity, sensitivity, negative predictive value, and accuracy was 85.7%, 100%, 100%, and 100%, respectively.Conclusions:This study indicates that lateral pelvic SLNB using ICG fluorescence navigation shows promise as a safe and feasible procedure with good accuracy. This technique may replace preventive LLND for locally advanced lower rectal cancer.
10.The clinical significance of lateral pelvic sentinel lymph node biopsy using indocyanine green fluorescence navigation in laparoscopic lateral pelvic lymph node dissection
Hao SU ; Zheng XU ; Mandula BAO ; Shou LUO ; Jianwei LIANG ; Wei PEI ; Xu GUAN ; Zheng LIU ; Zheng JIANG ; Mingguang ZHANG ; Zhixun ZHAO ; Weisen JIN ; Haitao ZHOU
Chinese Journal of Oncology 2024;46(2):140-145
Objectives:This study aims to explore the clinical significance of lateral pelvic sentinel lymph node biopsy (SLNB) using indocyanine green (ICG) fluorescence navigation in laparoscopic lateral pelvic lymph node dissection (LLND) and evaluate the accuracy and feasibility of this technique to predict the status of lateral pelvic lymph nodes (LPLNs).Methods:The clinical and pathological characteristics, surgical outcomes, lymph node findings and perioperative complications of 16 rectal cancer patients who underwent SLNB using ICG fluorescence navigation in laparoscopic LLND in the Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College during April 2017 and October 2022 were retrospectively collected and analyzed. The patients did not receive preoperative neoadjuvant radiotherapy and presented with LPLNs but without LPLN enlargement (MRI showed the maximum short axes of the LPLNs were ≥5 mm and <10 mm at first visit).Results:All 16 patients were successfully performed SLNB using ICG fluorescence navigation in laparoscopic LLND. Three patients underwent bilateral LLND and 13 patients underwent unilateral LLND. The lateral pelvic sentinel lymph nodes (SLNs) were clearly fluorescent before dissection in 14 patients and the detection rate of SLNs for these patients was 87.5%. Lateral pelvic SLN metastasis was diagnosed in 2 patients and negative results were found in 12 patients by frozen pathological examinations. Among the 14 patients in whom lateral pelvic SLNs were detected, the dissected lateral pelvic non-SLNs were all negative. All dissected LPLNs were negative in two patients without fluorescent lateral pelvic SLNs. The specificity, sensitivity, negative predictive value, and accuracy was 85.7%, 100%, 100%, and 100%, respectively.Conclusions:This study indicates that lateral pelvic SLNB using ICG fluorescence navigation shows promise as a safe and feasible procedure with good accuracy. This technique may replace preventive LLND for locally advanced lower rectal cancer.


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