1.Metagenomics of Fecal Gut Microbiota in Common Traditional Chinese Medicine Syndrome Types of Irritable Bowel Syndrome with Diarrhea:A Cross-sectional Study
Qin XIONG ; Yilin LI ; Chengjiao YAO ; Lihong LUO ; Fengjiao XIE ; Chunrong YANG ; Chaoqiang DONG ; Peimin FENG
Journal of Traditional Chinese Medicine 2024;65(5):503-511
ObjectiveTo investigate the structural and functional characteristics of gut microbiota in common traditional Chinese medicine (TCM) syndromes of irritable bowel syndrome with diarrhea (IBS-D). MethodsIBS-D patients who visited the Hospital of Chengdu University of Traditional Chinese Medicine, and healthy participants from the Physical Examination Centre of the same hospital were recruited from 1st January 2020 to 31st March 2021.The IBS-D patients were classified into syndrome of liver constraint and spleen deficiency, and syndrome of spleen deficiency and dampness exuberance; together with the recruited healthy participants, there were liver-constraint group, dampness-exuberance group, and healthy group. General information, including age, gender and body mass index (BMI), were collected, and Irritable Bowel Syndrome Symptom Severity Scale (IBS-SSS) as well as Irritable Bowel Syndrome Quality of Life Scale (IBS-QOL) scores were additionally collected from IBS-D patients. Fresh fecal samples were also collected and tested by macro-genome sequencing technology for abundance statistical display, PCoA, Anosim, LEfSe bioinformatic analysis of the annotated gut microbiota structure and function. ResultsThere was no statistically significant difference in the general information of the participants in the three groups (P>0.05); the difference in the IBS-SSS and IBS-QOL scores between liver-constraint group and dampness-exuberance group were not statistically significant (P>0.05). The study included 28 cases each in liver-constraint group, dampness-exuberance group, and healthy group. The number of specific genes to patients in liver-constraint group was 269 135, with 216 156 in dampness-exuberance group and 249 759 in healthy group, accounting of total 1 784 036 in the three groups. There were differences in the relative abundance distribution of the top ten species of gut microbiota among the three groups, with smaller differences at the phylum, class and order levels, and larger differences at the family, genus and species levels. There were differences in the relative abundance of structure and function of the gut microbiota among the three groups. Species PCoA and Anosim analyses at the species level showed significant differences in the composition of the microbiota among the three groups. Further LEfSe analyses showed that patients in liver-constraint group were screened for 14 dominant strains, of which Clostridium sp. CAG 217, Lachnospira pectinoschiza, Anaerotruncus sp. CAG 528, Paeniclostridium sordellii, Eubecterium sp. CAG 76, Bacillus cereus were affected to a greater extent in abundance differences; dampness-exuberance group screened 24 species of dominant bacteria, of which Roseburia inulinivorans, Eubacterium sp. CAG 251, Roseburia hominis, Unclassified Eubacterium rectale, Roseburia intestinalis, and Megamonas funiformis were affected to a greater extent in abundance differences; no dominant functional genes were screened for patients in liver-constraint group, and dampness-exuberance group was screened for flagellum assembly (ko02040), porphyrin metabolism ( ko00860), salmonella infection (ko05132), and benzoic acid degradation (ko00362). The differentially dominant functional genes in liver-constraint group and dampness-exuberance group may mainly focus on metabolism (including biodegradation and metabolism of exogenous substances, energy metabolism, lipid metabolism, etc.). ConclusionIBS-D with syndrome of liver constraint and spleen deficiency is characterized by the enrichment of 14 gut microbiota, such as Clostridium sp. CAG 217, while IBS-D with syndrome of spleen deficiency and dampness exuberance is characterized by the enrichment of 24 gut microbiota, such as Roseburia inulinivorans, and 4 functional enrichments, such as flagellum assembly. Clostridium sp. CAG 217 and Roseburia inulinivorans are expected to be biomarkers for IBS-D patients in the two syndromes, respectively.
2.Evaluation of the operational efficiency of oncology department in a multi-campus public hospital based on the super efficiency DEA-Malmquist index model
Changyu QU ; Juming LIU ; Yusha GONG ; Qin YANG ; Yongxiang GONG ; Tiemei HE ; Xiaodong LIU ; Tienan YI ; Chunrong HUANG
Chinese Journal of Hospital Administration 2024;40(5):387-392
Objective:To analyze the operational efficiency of the oncology department in multi-campus hospital, providing reference for rational resource allocation and efficiency enhancement.Methods:A certaion tertiary grade A Hospital is a multi-campus public hospital with integrated management. This study focused on its oncology department, with 9 wards located in different campus as decision-making units. Data from 2020 to 2022 were extracted from the hospital′s medical records management system, disease diagnosis-related groups management system, and hospital information system. The super-efficiency DEA model and Malmquist index model were used to evaluate efficiency variations of the oncology department in different time slots and decision-making units. Identifying input redundancies and output deficiencies in wards not achieving constant returns to scale through projection value analysis. Selecting the total number of medical staff and the actual total number of bed-days occupied as input indicators, while bed utilization rate, discharge rate, and case mix index as output indicators.Results:From 2020 to 2022, the wards with a DEA super-efficiency value greater than 1 were 0, 2, and 4, respectively, showing a gradual increase in overall efficiency. In 2022, wards S3, S4, S7, and S9 achieved constant returns to scale with super-efficiency values of 1.001, 1.005, 1.113, and 1.112, respectively. The other five wards had zero input redundancy, but some suffered from insufficient outputs. For example, wards S5 and S8 should increase their bed utilization rates by 5% and 4%, respectively. Wards S1 and S8 needed to increase their annual discharge numbers by 24% and 1%, respectively, while wards S2 and S6 should increase their annual case mix index by 21% and 20%, respectively. From 2020 to 2021, the Malmquist index of the oncology department was 0.959, while from 2021 to 2022 it rose to 1.030, and the Malmquist index of each ward was greater than 1.Conclusions:By implementing integrated management across multiple campus, the operational efficiency of the oncology department has been comprehensively improved. The use of the super efficient DEA-Malmquist index model to evaluate the operational efficiency of departments has practical significance.
3.Comparison of emotional and behavioral problems of only and non only child in the kindergartens in Chengdu
REN Yan, ZHU Diling, YE Liwen, LI Chunrong, CHEN Yue, YANG Liu, QIN Chengjie, LUO Tongyong
Chinese Journal of School Health 2023;44(5):733-737
Objective:
To analyze the emotional and behavioral problems and associated factors of the only and non only child, and to provide some clues for further monitoring and intervention of psychological and behavioral development among preschool children.
Methods:
Using a convenience sampling method, a total of 45 065 children enrolled in 153 kindergartens in 23 districts and counties of Chengdu were selected from May to June 2021 to investigate demographic characteristics and children s psycho behavioral development through online questionnaires filled out by their guardians. The Chi square tests were used to analyze whether the differences in abnormality rates of each dimension were statistically significant between the only and non only children. The emotional and behavioral problems of only children and non only children were analyzed by propensity score measurement.
Results:
The detection rate of abnormal emotional behavior problems in children was 6.10%, including 6.34% in the only child group and 5.84 % in the non only child group. After matching, total difficulty score, and scores of emotional symptoms, conduct problems, hyperactive attention deficit, peer interaction, and social behavior differed between the only child group and the non only child group ( t =9.91, 8.97, 3.91, 15.57, -5.46, 4.08, P <0.01).
Conclusion
In terms of the total score of difficulties, emotional symptoms, moral problems, and hyperactivity attention defects, the non only child is better than the only child,but the opposite is true in terms of peer interaction and social behavior. Mental health conditions among the only child should be paid more attention. Whether or not the only child should be taken as an important consideration for preschool children s mental health care.
4.Application of self-made multifunctional accessory stent in endoscopic mucosal dissection
Chunrong MO ; Xueqiang HE ; Shengai ZHONG ; Huajun LI ; Yu HU ; Lu QIN ; Shuihuan LU ; Lin WANG ; Hong XIONG ; Shuiying ZHOU
Chinese Journal of Practical Nursing 2022;38(1):45-49
Objective:To investigate the safety and efficacy of self-made multifunctional endoscopic instrument accessory stent in endoscopic mucosal dissection (ESD).Methods:A total of 80 patients who received ESD in 924th Hospital of Joint Logistic Support Force of Chinese People′s Liberation Army from May 2019 to February 2021 were selected as research object. Random number table method was used to divide patients into control group and experimental group, 40 cases in each group. The experimental group used self-made endoscopic instrument accessory stent, and the control group did not use self-made endoscopic instrument accessory stent. The length of operation, the number of instruments taken by mistake, the number of instruments polluted during operation and the infection of postoperative 3-7 days under the same operation position, operating doctors and nurses were analyzed and compared between the two groups.Results:The incidence of instruments taken by mistake, the incidence of instruments polluted during operation and the infection rate of postoperative 3-7 days were 0.9% (8/856), 1.4% (12/856) and 2.5% (1/40) in the experimental group, which in the control group were 10.8% (96/887), 11.8% (105/887) and 15.0% (6/40) respectively, there were significant differences between the two groups ( χ2=75.92, 75.76, 3.91, all P<0.05). The length of operation in the experimental group was (51.56 ± 2.32) min, and that in the control group was (79.02 ± 2.83) min, the difference was statistically significant ( t=-8.72, P<0.05). Conclusions:When the patients underwent ESD surgery, the self-made multifunctional accessory stent was used to place the required instrument accessory. The length of operation was shorter, the incidence of instruments taken by mistake, the incidence of instruments polluted during operation and the infection rate of postoperative 3-7 days were reduced, the quality of minimally invasive endoscopic surgery was improved.
5.Influence of morphological features of oval foramen in Dyna-CT three-dimensional imaging in percutaneous balloon compression
Jing LYU ; Peng ZHAO ; Xin HU ; Chunrong QIN ; Ruilin HE ; Zongbin JIANG
Chinese Journal of Neuromedicine 2022;21(7):671-676
Objective:To investigate the influences of morphological characteristics of skull base ovale foramen in the puncture difficulty of percutaneous balloon compression (PBC), surgical efficacy and postoperative complications in patients with idiopathic trigeminal neuralgia (ITN).Methods:One hundred and twenty-seven patients with ITN, admitted to our hospital from January 2020 to January 2021, were collected. Dyna-CT three-dimensional imaging of the oval foramen at the skull base and PBC treatment were performed on the included patients, and the morphological data of the oval foramen were measured. Numeric Rating Scale (NRS) was used to assess pain degrees before and after surgery. The differences of cross-sectional area and exposure Angle, puncture difficulty and time, NRS scores before and after surgery and incidence of complications were compared in patients with ovale foramen at different forms. The correlations of puncture time with puncture difficulty and cross-sectional area of ovale foramen in skull base were analyzed.Results:The foramen ovale in skull base of 127 patients included standard oval shape ( n=82), almond shape ( n=9), narrow and long shape ( n=13), fissure shape ( n=8) and irregular shape ( n=15). Different morphological characteristics of the skull base ovale foramen could lead to significant differences in the difficulty of puncture, exposure angle, cross-sectional area and puncture time ( P<0.05). Puncture time was positively correlated with puncture difficulty and cross-sectional area ( r=0.359, P<0.001; r=0.280, P=0.007). The patients with skull base ovale foramen of different forms showed no significant differences in the differences of NRS scores before and after PBC and occurrence of postoperative complications ( P>0.05). Conclusion:Dyna-CT three-dimensional imaging can visually display the morphological characteristics of the oval foramen at the skull base; this technique can be used to guide the puncture of the oval foramen and effectively evaluate the difficulty of puncture in PBC, but it does not affect the postoperative pain improvement and complication incidences.
6.Comparing the clinical characteristics and prognosis of seropositive and seronegative rheumatoid arthritis patients in China: a real-world study
Yehua JIN ; Ting JIANG ; Xiaolei FAN ; Rongsheng WANG ; Yuanyuan ZHANG ; Peng CHENG ; Yingying QIN ; Mengjie HONG ; Mengru GUO ; Qingqing CHENG ; Zhaoyi LIU ; Runrun ZHANG ; Cen CHANG ; Lingxia XU ; Linshuai XU ; Ying GU ; Chunrong HU ; Xiao SU ; Luan XUE ; Yongfei FANG ; Li SU ; Mingli GAO ; Jiangyun PENG ; Qianghua WEI ; Jie SHEN ; Qi ZHU ; Hongxia LIU ; Dongyi HE
Chinese Journal of Rheumatology 2021;25(5):307-315
Objective:In general, patients with seropositive rheumatoid arthritis (RA) are considered to show an aggressive disease course. However, the relationship between the two subgroups in disease severity is controversial. Our study is aimed to compare the clinical characteristics and prognosis of double-seropositive and seronegative RA in China through a real-world large scale study.Methods:RA patients who met the 1987 American College of Rheumatology (ACR) classification criteria or the 2010 ACR/European Anti-Rheumatism Alliance RA classification criteria, and who attended the 10 hospitals across the country from September 2015 to January 2020, were enrolled. According to the serological status, patients were divided into 4 subgroups [rheumatoid factor (RF)(-) anti-cyclic citrullinated peptide (CCP) antibody (-), RF(+), RF(+) anti-CCP antibody(+), anti-CCP antibody(+)] and compared the disease characteristics and treatment response. One-way analysis of variance was used for measurement data that conformed to normal distribution, Kruskal-Wallis H test was used for measurement data that did not conform to normal distribution; paired t test was used for comparison before and after treatment within the group if the data was normally distributed else paired rank sum test was used; χ2 test was used for count data. Results:① A total of 2 461 patients were included, including 1 813 RF(+) anti-CCP antibody(+) patients (73.67%), 129 RF(+) patients (5.24%), 245 RF(-) anti-CCP antibody(-) patients (9.96%), 74 anti-CCP antibody(+) patients (11.13%). ② Regardless of the CCP status, RF(+) patients had an early age of onset [RF(-) anti-CCP antibody(-) (51±14) years old, anti-CCP antibody(+) (50±15) years old, RF(+) anti-CCP antibody(+) (48±14) years old, RF(+)(48±13) years old, F=3.003, P=0.029], longer disease duration [RF(-) anti-CCP antibody(-) 50 (20, 126) months, anti-CCP antibody(+) 60(24, 150) months, RF(+) anti-CCP antibody(+) 89(35, 179) months, RF(+) 83(25, 160) months, H=22.001, P<0.01], more joint swelling counts (SJC) [RF(-) anti-CCP antibody(-) 2(0, 6), Anti-CCP antibody(+) 2(0, 5), RF(+) anti-CCP antibody(+) 2(0, 7), RF(+) 2(0, 6), H=8.939, P=0.03] and tender joint counts (TJC) [RF(-) anti-CCP antibody(-) 3(0, 8), anti-CCP antibody(+) 2(0, 6), RF(+) anti-CCP antibody(+) 3(1, 9), RF(+) 2(0, 8), H=11.341, P=0.01] and the morning stiff time was longer [RF(-) anti-CCP antibody(-) 30(0, 60) min, anti-CCP antibody(+) 20(0, 60) min, RF(+) anti-CCP antibody(+) 30(10, 60) min, RF(+) 30(10, 60) min, H=13.32, P<0.01]; ESR [RF(-) anti-CCP antibody(-) 17(9, 38) mm/1 h, anti-CCP antibody(+) 20(10, 35) mm/1 h, RF(+) anti-CCP antibody(+) 26(14, 45) mm/1 h, RF(+) 28(14, 50) mm/1 h, H=37.084, P<0.01] and CRP [RF(-) anti-CCP antibody(-) 2.3 (0.8, 15.9) mm/L, Anti-CCP antibody(+) 2.7(0.7, 12.1) mm/L, RF(+) anti-CCP antibody(+) 5.2(1.3, 17.2) mm/L, RF (+) 5.2(0.9, 16.2) mm/L, H=22.141, P<0.01] of the RF(+)patients were significantly higher than RF(-) patients, and RF(+) patients had higher disease severity(DAS28-ESR) [RF(-) anti-CCP antibody(-) (4.0±1.8), anti-CCP antibody(+) (3.8±1.6), RF(+) anti-CCP antibody(+) (4.3±1.8), RF(+) (4.1±1.7), F=7.269, P<0.01]. ③ The RF(+) anti-CCP antibody(+) patients were divided into 4 subgroups, and it was found that RF-H anti-CCP antibody-L patients had higher disease severity [RF-H anti-CCP antibody-H 4.3(2.9, 5.6), RF-L anti-CCP antibody-L 4.5(3.0, 5.7), RF-H anti-CCP antibody-L 4.9(3.1, 6.2), RF-L anti-CCP antibody-H 2.8(1.8, 3.9), H=20.374, P<0.01]. ④ After 3-month follow up, the clinical characteristics of the four groups were improved, but there was no significant difference in the improvement of the four groups, indicating that the RF and anti-CCP antibody status did not affect the remission within 3 months. Conclusion:Among RA patients, the disease activity of RA patients is closely related to RF and the RF(+) patients have more severe disease than RF(-) patients. Patients with higher RF titer also have more severe disease than that of patients with low RF titer. After 3 months of medication treatment, the antibody status does not affect the disease remission rate.
7.Application of discharge key task plan in patients undergoing lumbar intervertebral fusion surgery
Haibing QIN ; Chunrong LI ; Aiyuan ZOU ; Zhaodian WU ; Chaoqun LIU ; Yong LI ; Lianhuan YANG
Chinese Journal of Modern Nursing 2021;27(30):4139-4143
Objective:To explore the effects of discharge key task plan in patients undergoing lumbar intervertebral fusion surgery.Methods:Totally 125 patients who underwent lumbar intervertebral fusion surgery in Zhuhai Hospital of Traditional Chinese Medicine from June 2018 to June 2019 were selected by convenient sampling and divided into an observation group and a control group according to the random number table. Patients in the observation group received interventions with the discharge key task plan, while patients in the control group received routine care. The discharge readiness, compliance of treatment behavior, and Oswestry Disability Index were collected and compared between the two groups of patients.Results:Finally, 123 patients completed the study, with 62 in the observation group and 61 in the control group. The total scores and scores of all dimensions of readiness to discharge in the observation group were higher than those in the control group ( P<0.05) . The compliance with treatment behavior in the observation group 24 hours before discharge and 3, 6 months after discharge were higher than those in the control group ( P<0.05) ; and the repeated measures analysis of variance showed that the compliance scores of the two groups shoed statistically significant difference in the intervention time, between the groups, and in interaction effects ( P<0.01) . The Oswestry Disability Index in the observation group was lower than that in the control group 3 and 6 months after discharge from the hospital ( P<0.05) ; and the repeated measures analysis of variance showed that the Oswestry Disability Index of the two groups showed statistically significant difference in terms of intervention time, inter-group, and interaction effects ( P<0.01) . Conclusions:The discharge key task plan helps to improve the discharge readiness and compliance with treatment behavior, and reduce the lumbar intervertebral dysfunction in patients undergoing lumbar intervertebral fusion surgery.
8.Value of absolute quantification of myocardial perfusion by PET in detecting coronary microvascular disease in patients with non-obstructive coronaries
Ping WU ; Xiaoshan GUO ; Xi ZHANG ; Zhifang WU ; Ruonan WANG ; Li LI ; Meng LIANG ; Hongliang WANG ; Min YAN ; Zhixing QIN ; Pengliang CHENG ; Chunrong JIN ; Minfu YANG ; Yuetao WANG ; Sijin LI
Chinese Journal of Cardiology 2020;48(3):205-210
Objective:To compare the incidence of coronary microvascular disease (CMVD) between patients with non-obstructive and obstructive coronary arteries.Methods:We retrospectively analyzed 97 patients with angina pectoris, who underwent the absolute quantitative PET examination of myocardial perfusion and coronary anatomy examination within 90 days. All patients were divided into two groups: non-obstructive group (72 cases, no stenosis ≥50% in all three coronary arteries) and obstructive group (25 cases, at least one coronary stenosis ≥50%; and at least one coronary stenosis<50%). Quantitative parameters derived from PET including rest myocardial blood flow (RMBF), stress myocardial blood flow (SMBF), coronary flow reserve (CFR) and cardiovascular risk factors were compared between the two groups. CMVD was defined as CFR<2.90 and SMBF <2.17 ml·min -1·g -1. Results:Incidence of CMVD was significant higher in the non-obstructive coronary arteries of the obstructive group than in the non-obstructive coronary arteries of non-obstructive group (47.1% (16/34) vs. 25.5% (55/216), χ 2=6.738, P=0.009) while incidence of CMVD was similar between non-obstructive and obstructive patients ((44% (11/25) vs. 33.3% (24/72), χ 2=0.915, P=0.339). RMBF ((0.83±0.14) ml·min -1·g -1 vs. (0.82±0.17) ml·min -1·g -1), SMBF ((2.13±0.60) ml·min -1·g -1 vs. (1.91±0.50) ml·min -1·g -1) and CFR (2.59±0.66 vs. 2.36±0.47) were similar between the two groups (all P>0.05). Conclusions:CMVD can occur in non-obstructive coronary arteries in both patients with non-occlusive coronary arteries and patients with obstructive coronary arteries. Prevalence of CMVD is significantly higher in patients with obstructive coronary arteries than in patients with non-obstructive coronary arteries. The CMVD severity is similar between the two groups.
9.Effects of astragaloside on TRPC6 expression on mouse podocyte induced by TGF-β1
Haiting HUANG ; Haohao WU ; Youling QIN ; Xu LIN ; Yanwu YOU ; Pengwei GUO ; Chunrong TANG
Chinese Journal of Immunology 2017;33(3):370-373
Objective:To explore the possible mechanism of astragaloside involved in the mouse podocytes injury induced by TGF-β1 in vitro.Methods:Mouse podocytes were cultured in vitro and then all cell were divided into 5 groups:normal control group , TGF-β1 treatment group ,TGF-β1 treatment +astragaloside low dose group ,TGF-β1 treatment +astragaloside middle dose group and TGF-β1 treatment +astragaloside high dose group.The proliferation rate of each group was investigated by MTT assay ,the expression of TRPC6 protein and mRNA were measured by Western blot and RT-PCR respectively after 48 hours.Results:TGF-β1 can significantly inhibit the proliferation of podocytes ( P<0.05) ,fusions of foot processes or even effaced of podocytes were observed .TGF-β1 could also increase the expression of TRPC6.Astragaloside could reduce the inhibition of TGF-β1 to the proliferain of podocytes significantly ,make the cell shape tend to be normal,and reduce the expression of TRPC6 mRNA and protein with dose-effect relation.Conclusion:TRPC6 play an impor-tant role in the TGF-β1 induecd podocytes injury .Astragaloside can alleviate podocytes injury by reduce the expression of TRPC 6.
10. Study of the association between polymorphism of persistent obesity, human leptin gene/leptin receptor gene and molecular subtypes of breast cancer
Xuelian YUAN ; Zhuping XU ; Chunrong LIU ; Lanping YAN ; Ping TAO ; Ping XIONG ; Qin LI ; Min ZHOU ; Hui LI ; Min ZHAO ; Jiayuan LI
Chinese Journal of Preventive Medicine 2017;51(6):533-538
Objectives:
To explore the association between the polymorphism of persistent obesity and genetic variations in the LEP (human leptin gene, LEP) and LEPR (leptin receptor gene, LEPR) genes and different molecular subtypes of breast cancer.
Methods:
All 703 female patients of breast cancer diagnosed by histopathology in the Sichuan Cancer Hospital or the West China Hospital, excluding patients with metastatic breast cancer or mental disease, were selected as cases from April 2014 to May 2015. At the same time, 805 healthy women received physical examination in medical examination center of Sichuan People Hospital or Shuangliu maternal and child health care hospital, excluding those with therioma, breast disease, and mental disease, were enrolled in control group. A uniform questionnaire was used to collect general information including demographic characteristic, reproductive history height, weight, and so on. And the obesity status in recent 10 years was judged. Time of Flight Mass Spectrometer was used to determine the genotypes of LEP rs7799039, LEPR rs1137100 and LEPR rs1137101, while the multinomial logistic regression analysis was conducted to estimate the effect of risk factors related to breast cancer in different molecular subtypes; and then, the association between polymorphism of persistent obesity, the LEP, LEPR genes and breast cancer of different molecular subtypes was analyzed by binary logistic regression models.
Results:
The average age of controls was (48.98±8.83) years old, while the age of cases of TNBC, Luminal A, Luminal B, and HER-2+ were (51.43±11.33), (49.94±10.10), (49.73±9.38), (50.50±9.04) years old, respectively. The frequency of genotype LEP rs7799039, LEPR rs1137100 and LEPR rs1137101 in control group was separately 74.8%(1 157/1 546), 83.6%(1 339/1 602) and 88.4%(1 416/1 602); while 77.6% (1 074/1 384), 82.4% (1 155/1 402) and 87.9% (1 232/1 402) respectively in case group. Compared with non-persistent obesity subjects, the persistent obesity ones showed an increased risk in TNBC (


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