1.Changing resistance profiles of Haemophilus influenzae and Moraxella catarrhalis isolates in hospitals across China:results from the CHINET Antimicrobial Resistance Surveillance Program,2015-2021
Hui FAN ; Chunhong SHAO ; Jia WANG ; Yang YANG ; Fupin HU ; Demei ZHU ; Yunsheng CHEN ; Qing MENG ; Hong ZHANG ; Chun WANG ; Fang DONG ; Wenqi SONG ; Kaizhen WEN ; Yirong ZHANG ; Chuanqing WANG ; Pan FU ; Chao ZHUO ; Danhong SU ; Jiangwei KE ; Shuping ZHOU ; Hua ZHANG ; Fangfang HU ; Mei KANG ; Chao HE ; Hua YU ; Xiangning HUANG ; Yingchun XU ; Xiaojiang ZHANG ; Wenen LIU ; Yanming LI ; Lei ZHU ; Jinhua MENG ; Shifu WANG ; Bin SHAN ; Yan DU ; Wei JIA ; Gang LI ; Jiao FENG ; Ping GONG ; Miao SONG ; Lianhua WEI ; Xin WANG ; Ruizhong WANG ; Hua FANG ; Sufang GUO ; Yanyan WANG ; Dawen GUO ; Jinying ZHAO ; Lixia ZHANG ; Juan MA ; Han SHEN ; Wanqing ZHOU ; Ruyi GUO ; Yan ZHU ; Jinsong WU ; Yuemei LU ; Yuxing NI ; Jingrong SUN ; Xiaobo MA ; Yanqing ZHENG ; Yunsong YU ; Jie LIN ; Ziyong SUN ; Zhongju CHEN ; Zhidong HU ; Jin LI ; Fengbo ZHANG ; Ping JI ; Yunjian HU ; Xiaoman AI ; Jinju DUAN ; Jianbang KANG ; Xuefei HU ; Xuesong XU ; Chao YAN ; Yi LI ; Shanmei WANG ; Hongqin GU ; Yuanhong XU ; Ying HUANG ; Yunzhuo CHU ; Sufei TIAN ; Jihong LI ; Bixia YU ; Cunshan KOU ; Jilu SHEN ; Wenhui HUANG ; Xiuli YANG ; Likang ZHU ; Lin JIANG ; Wen HE ; Chunlei YUE
Chinese Journal of Infection and Chemotherapy 2025;25(1):30-38
Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91%of the total clinical isolates and 4.07%of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89%were isolated from children and 33.11%were isolated from adults.More than 90%of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79%in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06%were isolated from children and 19.94%isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0%.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.
2.Research Progress on Iron Overload and Pancreatic β-Cell Dysfunction
Yanyan WU ; Mei HUANG ; Wencan JIANG ; Mei ZHANG
Chinese Journal of Geriatrics 2025;44(4):429-434
Pancreatic β-cell dysfunction is a critical factor in the pathogenesis of type 2 diabetes mellitus(T2DM).Recent studies have identified iron overload as a significant risk factor for T2DM, wherein excess iron contributes to β-cell dysfunction through multiple pathways, including oxidative stress, mitochondrial dysfunction, and a reduction in the number of pancreatic β-cells.These mechanisms adversely affect insulin synthesis, secretion, and release.This review aims to summarize the recent advancements in understanding the relationship between iron overload and pancreatic β-cell dysfunction.
3.Changing resistance profiles of Haemophilus influenzae and Moraxella catarrhalis isolates in hospitals across China:results from the CHINET Antimicrobial Resistance Surveillance Program,2015-2021
Hui FAN ; Chunhong SHAO ; Jia WANG ; Yang YANG ; Fupin HU ; Demei ZHU ; Yunsheng CHEN ; Qing MENG ; Hong ZHANG ; Chun WANG ; Fang DONG ; Wenqi SONG ; Kaizhen WEN ; Yirong ZHANG ; Chuanqing WANG ; Pan FU ; Chao ZHUO ; Danhong SU ; Jiangwei KE ; Shuping ZHOU ; Hua ZHANG ; Fangfang HU ; Mei KANG ; Chao HE ; Hua YU ; Xiangning HUANG ; Yingchun XU ; Xiaojiang ZHANG ; Wenen LIU ; Yanming LI ; Lei ZHU ; Jinhua MENG ; Shifu WANG ; Bin SHAN ; Yan DU ; Wei JIA ; Gang LI ; Jiao FENG ; Ping GONG ; Miao SONG ; Lianhua WEI ; Xin WANG ; Ruizhong WANG ; Hua FANG ; Sufang GUO ; Yanyan WANG ; Dawen GUO ; Jinying ZHAO ; Lixia ZHANG ; Juan MA ; Han SHEN ; Wanqing ZHOU ; Ruyi GUO ; Yan ZHU ; Jinsong WU ; Yuemei LU ; Yuxing NI ; Jingrong SUN ; Xiaobo MA ; Yanqing ZHENG ; Yunsong YU ; Jie LIN ; Ziyong SUN ; Zhongju CHEN ; Zhidong HU ; Jin LI ; Fengbo ZHANG ; Ping JI ; Yunjian HU ; Xiaoman AI ; Jinju DUAN ; Jianbang KANG ; Xuefei HU ; Xuesong XU ; Chao YAN ; Yi LI ; Shanmei WANG ; Hongqin GU ; Yuanhong XU ; Ying HUANG ; Yunzhuo CHU ; Sufei TIAN ; Jihong LI ; Bixia YU ; Cunshan KOU ; Jilu SHEN ; Wenhui HUANG ; Xiuli YANG ; Likang ZHU ; Lin JIANG ; Wen HE ; Chunlei YUE
Chinese Journal of Infection and Chemotherapy 2025;25(1):30-38
Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91%of the total clinical isolates and 4.07%of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89%were isolated from children and 33.11%were isolated from adults.More than 90%of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79%in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06%were isolated from children and 19.94%isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0%.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.
4.Research Progress on Iron Overload and Pancreatic β-Cell Dysfunction
Yanyan WU ; Mei HUANG ; Wencan JIANG ; Mei ZHANG
Chinese Journal of Geriatrics 2025;44(4):429-434
Pancreatic β-cell dysfunction is a critical factor in the pathogenesis of type 2 diabetes mellitus(T2DM).Recent studies have identified iron overload as a significant risk factor for T2DM, wherein excess iron contributes to β-cell dysfunction through multiple pathways, including oxidative stress, mitochondrial dysfunction, and a reduction in the number of pancreatic β-cells.These mechanisms adversely affect insulin synthesis, secretion, and release.This review aims to summarize the recent advancements in understanding the relationship between iron overload and pancreatic β-cell dysfunction.
5.Effect of Fuzheng Huayu prescription on hepatocyte extinction and regeneration in a mouse model of liver cirrhosis
Tingting ZHU ; Jingshu QI ; Yanan GUO ; Hongliang LIU ; Yanyan TAO ; Zhimin ZHAO ; Zhengxin LI ; Chenghai LIU
Journal of Clinical Hepatology 2024;40(4):745-752
ObjectiveTo investigate the effect of Fuzheng Huayu prescription on hepatocyte extinction and regeneration in fibrotic liver and its mechanism of action in promoting hepatocyte regeneration. MethodsMice were given intraperitoneal injection of CCl4 for 6 weeks to establish a model of liver cirrhosis, and there were 10 mice in the model group, 10 in the sorafenib group, 10 in the Fuzheng Huayu prescription group, and 9 in the normal control group. Since week 4 of modeling, the mice in the Fuzheng Huayu prescription group and the sorafenib group were given the corresponding drug by gavage at a dose of 4.8 g/kg and 4 mg/kg, respectively, for three consecutive weeks, and those in the normal group and the model group were given an equal volume of sodium carboxymethyl cellulose. Serum liver function parameters were measured; the METAVIR scoring system was used to evaluate liver inflammation and fibrosis stage; Sirius Red staining and hydroxyproline (Hyp) content in liver tissue were used to evaluate collagen deposition; immunohistochemistry was used to measure the protein expression levels of type IV collagen, CD31, CD32b, Ki67, CyclinD1, glutamine synthetase, Wnt2, and HGF, and Western blot was used to measure the expression levels of Wnt2, LRP6, β-catenin, p-β-catenin, and CyclinD1 in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the model group, the Fuzheng Huayu prescription group and the sorafenib group showed the following changes: significant reductions in the serum levels of alanine aminotransferase and aspartate aminotransferase and the content of Hyp in liver tissue (all P<0.01); a significant reduction in METAVIR score; significant reductions in the expression levels of type Ⅳ collagen and CD31 (all P<0.05) and a significant increase in the expression level of CD32b (P<0.01); significant reductions in the number of parenchymal extinction lesions and significant increases in the expression levels of Ki67 and CyclinD1 in liver tissue (all P<0.01); significant increases in the protein expression levels of Wnt2, LRP6, β-catenin, and CyclinD1 and a significant reduction in the protein expression level of p-β-catenin (all P<0.05); significant increases in the number of cells stained positive for both CD32b and Wnt2. ConclusionFuzheng Huayu prescription can inhibit hepatic sinusoidal capillarization, improve the Wnt2 exocrine function of liver sinusoidal endothelial cells, activate the Wnt/β-catenin signaling pathway associated with hepatocyte regeneration, and finally reverse liver cirrhosis.
6.Establishment and evaluation of early prediction models for severe acute pancreatitis
Mei WANG ; Yu XIA ; Changmei WU ; Lianghui MA ; Yanyan CHEN ; Wenjun ZHU ; Xingyu WANG
Chinese Journal of Emergency Medicine 2024;33(10):1398-1406
Objective:To explore a simplified and efficient early prediction model for severe acute pancreatitis (SAP) using the least absolute shrinkage and selection operator (LASSO) regression, and to construct both logistic regression and decision tree models. The aim is to identify high-risk individuals, guide clinical treatment, and improve patient outcomes.Methods:A retrospective analysis was conducted on the clinical data of 412 patients with acute pancreatitis admitted to the Emergency and Gastroenterology Departments of the First Affiliated Hospital of Anhui Medical University and its High-tech Branch from November 2020 to September 2023. LASSO regression was employed to identify factors significantly associated with SAP, followed by the construction of a multivariate logistic regression model and a decision tree model. The predictive performance of these models was evaluated and compared to the bedside index for severity in acute pancreatitis (BISAP).Results:Among the 412 patients, the incidence of SAP was 12.14% ( n=50). Seven variables significantly associated with SAP severity were identified by LASSO regression, including respiratory rate at admission, pain score at admission, pleural effusion, fibrin degradation products, C-reactive protein, serum creatinine, and serum albumin. The logistic regression model incorporated four variables: pleural effusion, pain score at admission, serum creatinine, and serum albumin. In the training set, the model demonstrated a sensitivity of 0.528, specificity of 0.984, accuracy (95% CI) of 0.928 (0.892-0.955), Kappa value of 0.606, and AUC (95% CI) of 0.920 (0.862-0.979). In the testing set, the model showed a sensitivity of 0.643, specificity of 0.925, accuracy (95% CI) of 0.891 (0.822-0.941), Kappa value of 0.519, and AUC (95% CI) of 0.923 (0.861-0.985). The decision tree model comprised three branches and four terminal nodes, indicating that serum creatinine, serum albumin, and pleural effusion could effectively predict SAP occurrence. In the training set, the decision tree model had a sensitivity of 0.500, specificity of 0.973, accuracy (95% CI) of 0.914 (0.876-0.944), Kappa value of 0.544, and AUC (95% CI) of 0.812 (0.731-0.894). In the testing set, the model exhibited a sensitivity of 0.500, specificity of 0.925, accuracy (95% CI) of 0.875 (0.802-0.928), Kappa value of 0.412, and AUC (95% CI) of 0.709 (0.565-0.853). The DeLong test revealed that in the training set, the AUC of the logistic regression model was significantly greater than that of the decision tree model ( P<0.01) and the BISAP score ( P<0.001), while the AUC difference between the decision tree model and the BISAP score was not statistically significant ( P=0.762). In the testing set, the AUC of the logistic regression model was again greater than that of the decision tree model ( P<0.01) and the BISAP score ( P=0.018), whereas the AUC of the decision tree model was lower than that of the BISAP score ( P=0.017). Conclusions:Both the logistic regression and decision tree models demonstrate good predictive value for SAP, and their combined use may provide valuable guidance for clinical practice.
7.Diagnosis and treatment of arrhythmogenic cardiomyopathy in children
Wenqian YE ; Yanyan XIAO ; Xiaokun JIANG ; Mei JIN ; Xiaofang WANG ; Wenhong DING
Chinese Journal of Pediatrics 2024;62(4):363-367
Objective:To summarize the clinical manifestations, experiences in diagnosis and treatment of arrhythmogenic cardiomyopathy (ACM) in children.Methods:A retrospective analysis of the clinical manifestations, laboratory tests, radiological features, treatment and follow-up results was conducted in 11 children diagnosed with ACM at the center of congenital heart disease, Beijing anzhen hospital from May 2010 to March 2022.Results:A total of 11 patients aged 2 to 16 years, including 5 males and 6 females were diagnosed with ACM. The clinical manifestations included decreased activity tolerance (7 patients), heart failure (4 patients), syncope or sudden death (3 patients), palpitation (3 patients), and chest tightness and pain (3 patients). Electrocardiogram showed right bundle branch block in 9 cases, paroxysmal ventricular tachycardia in 4 cases, frequent premature ventricular contraction in 4 cases, ventricular pre-excitation in 1 case, left bundle branch block in 1 case, and first degree atrioventricular block in 2 cases. Echocardiography showed enlargement of the right heart, widening of the right ventricular outflow tract, and thinning and bulging of the local wall of the right ventricle with reduced pulsation. Ventricular thrombosis was found in 2 cases. Six children underwent cardiac magnetic resonance imaging, which mainly showed severe enlargement of the right heart, thin free wall of the right ventricle, decreased right heart function, enhanced right ventricular myocardium, and formation of right ventricular aneurysm. Two children underwent myocardial biopsy examination and presented with typical pathological changes of ACM. Genetic tests in five patients revealed DSG2 gene mutation in 2 cases, PKP2 gene mutation in 2 cases, and MYH6 gene mutation in 1 case. All patients received anti heart failure treatment and antiarrhythmic drugs. Two children received anticoagulant treatment due to ventricular thrombosis. Radiofrequency ablation was performed in 2 patients. Glenn procedure was performed in 4 patients, and heart transplantation was performed in 1 patient due to progressive heart failure. The follow-up period ranged from 6 months to 12 years. Two cases died of right heart failure, 6 cases had different degrees of heart failure, 1 case had intermittent chest tightness and pain, and 2 cases were stable.Conclusions:ACM is a progressive genetic cardiomyopathy characterized by decreased activity tolerance, cardiac failure and arrhythmia in pediatric patients. The diagnosis is mainly based on clinical manifestations, electrocardiogram, cardiac imaging changes, and genetic testing. Early detection, diagnosis, and personalized treatment can improve the prognosis.
8.Effect of remnant cholesterol levels on carotid intima thickness in patients with type 2 diabetes mellitus evaluated by ultra-high frequency ultrasound
Yiming MA ; Jianjun YUAN ; Mei ZHANG ; Yanyan GUO ; Rui XU ; Yanyan ZHANG ; Han ZHANG ; Xijun ZHANG ; Haohui ZHU
Chinese Journal of Ultrasonography 2023;32(6):508-514
Objective:To discuss the effect of remnant cholesterol (RC) levels on carotid intima thickness (CIT) in patients with type 2 diabetes mellitus (T2DM) by ultra-high frequency ultrasound.Methods:A total of 60 patients with T2DM who received treatment in Henan Provincial People′s Hospital from May 2021 to July 2022 were prospectively recruited, and they were divided into a higher RC group (31 cases) and a lower RC group (29 cases) according to the RC levels. Thirty-one age, sex and body mass index(BMI)-matched healthy volunteers were selected as control group. Carotid CIT, carotid media thickness(CMT) and intima-media thickness(CIMT) were measured by 24 MHz ultra-high frequency ultrasound probe. The difference of general clinical data, laboratory indicators and CIMT, CIT, CMT among the three groups were compared, and the influencing factors of CIT in T2DM patients were explored by multivariate regression analysis.Results:①There were no statistical significances in gender, age, BMI, high-density lipoprotein cholesterol (HDL-C) and CMT among the three groups (all P>0.05). There were no statistical significances in duration of diabetes, fasting blood-glucose and glycated haemoglobin between the two subgroups of T2DM (all P>0.05). ②Compared with the control group, CIMT and CIT were thicker in the T2DM group (both P<0.05). ③CIT was thicker in the higher RC group than in the lower RC group ( P<0.05), while the difference of CIMT was not statistically significant the two groups ( P>0.05). ④Multivariate regression analysis showed that RC was the influence factor of CIT in patients with T2DM(β=0.610, P=0.005). Conclusions:CIT is significantly thicker in T2DM patients with higher RC than in those with lower RC, and RC is the influence factor of CIT, which suggests that more attention should be paid to the detection of RC in T2DM patients.
9.Effects of segmented individualized jumping training in patients with ureteral calculi
Yanyan LIU ; Mei WANG ; Jijian SUN
Chinese Journal of Modern Nursing 2023;29(1):30-34
Objective:To explore the effect of segmented individualized jumping training on promoting the excretion of ureteral calculi.Methods:From January to December 2020, 87 patients with ureteral calculi admitted to the Urology Surgery of Henan Province Hospital of Traditional Chinese Medicine were selected as the research object by convenient sampling. The patients from January to June 2020 were set as the control group ( n=42) , and the patients from July to December 2020 were set as the observation group ( n=45) . The control group was given routine nursing, while the observation group was given segmented individualized jumping training on the basis of the control group. The effect, adverse reaction and pain of stone excretion were compared between the two groups. Results:In the observation group, the stone free rate was 91.11% (41/45) , the first stone excretion time was (2.04±0.58) days, and the stone free time was (11.05±4.16) days. In the control group, the stone free rate was 71.43% (30/42) , the first stone excretion time was (3.91±0.80) days, and the stone free time was (18.26±3.55) days. The above differences were statistically significant ( P<0.05) . No patient in the observation group had infection, one patient had gross hematuria, three patients relapsed to surgery. In the control group, five patients had infection, seven patients had gross hematuria, and ten patients relapsed to surgery, and the differences were statistically significant ( P<0.05) . The pain score of the observation group was lower than that of the control group five days after admission, with a statistically significant difference ( P<0.05) . Conclusions:Segmented individualized jumping training can accelerate the excretion of small stones in patients with ureteral calculi, reduce the adverse reactions in the process of stone excretion, and reduce the recurrence to surgery rate.
10.Syndrome and Treatment Rules of Traditional Chinese Medicine in Treating Chronic Obstructive Pulmonary Disease Based on Modern Medical Cases
Simin PENG ; Mei ZHAO ; Guanglan XU ; Yanyan ZHANG ; Lin WANG ; Kai PEI ; Mei HONG
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(15):173-182
ObjectiveTo explore the syndrome and treatment rules of traditional Chinese medicine (TCM) in treating chronic obstructive pulmonary disease (COPD) based on the medical literature and cases with the help of TCM inheritance support system platform (V2.5), thus providing new ideas for TCM to treat COPD. MethodThe medical cases of TCM treating COPD were retrieved from China national knowledge infrastructure (CNKI), Wanfang Database, and VIP China Science and Technology Journal Database. The medical cases that met the inclusion literature were collected in a new Word document, and then input into the TCM inheritance support system platform (V2.5) after data standardization. With the help of the algorithm carried by this software, the frequency statistics of "symptoms, syndrome types of TCM, Chinese medicine, and meridians of Chinese medicine" in the included COPD medical cases were performed, and the correlation analysis of the "prescription rules" in the included medical cases was carried out, thus excavating the potential core drug pairs and new prescriptions for the treatment of COPD. ResultA total of 103 articles were included with 126 medical cases and 131 diagnoses and treatments. According to statistics, the common symptoms of COPD were cough, expectoration, chest tightness, and asthma, and the common TCM syndromes included phlegm-heat obstructing lung, phlegm and blood stasis blocking lung, and lung-spleen Qi deficiency. The common TCM treatment methods included clearing heat and resolving phlegm, banking up earth to generate metal, and descending adverse and relieving dyspnea, among which the high-frequency Chinese medicines for the treatment of COPD were Pinelliae Rhizoma, Armeniacae Semen Amarum, Ephedrae Herba, Citri Reticulatae Pericarpium, and so on. The commonly used drug pairs included Asari Radix et Rhizoma-Pinelliae Rhizoma, Pinelliae Rhizoma-Schisandrae Chinensis Fructus-Glycyrrhizae Radix et Rhizoma, etc. Twelve new prescriptions for the treatment of COPD were found. ConclusionTCM believes that COPD is a lung disease formed by external evil, phlegm, blood stasis, and other pathological factors, with cough, phlegm, and asthma as the main symptoms. The main syndromes of COPD are phlegm-heat obstructing lung, phlegm and blood stasis blocking lung, and lung-spleen qi deficiency. "Strengthening the upright and dispelling evil" is the basic principle of the treatment COPD. In clinical, TCM methods with dispelling phlegm and removing blood stasis, and tonifying lung, spleen, and kidney should be adopted to treat COPD.

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