1.Laparoscopic surgery for high-risk prostate cancer:urinary and oncologic outcomes of vesicourethral anastomosis with maximal urethral length and bladder neck preservation
Kun ZHENG ; Xiaoyong HU ; Qiang FU ; Wang LI ; Ying WANG ; Nailong CAO ; Jiasheng CHEN ; Ranxing YANG
Journal of Modern Urology 2024;29(7):612-616
Objective To explore the application value of vesicourethral anastomosis with maximal urethral length preservation(MULP)and bladder neck preservation(BNP)in laparoscopic radical prostatectomy(LRP)or robot-assisted laparoscopic radical prostatectomy(RALP)for high-risk prostate cancer(HRPC)in terms of early urinary continence and oncology.Methods Clinical data of 23 HRPC patients who underwent LRP(including RALP)with MULP and BNP in our hospital during May 2022 and Jan.2024 were retrospectively analyzed.Patients'basic information,surgical parameters,postoperative complications,oncological outcomes and urinary incontinence were collected and analyzed.Results All operations were completed successfully without conversion to open surgery.The operation time was(108±31)min,average blood loss(112±45)mL,hospital stay(5.5±1.5)days,urethral catheterization time(12.6±1.8)days,and no patient received blood transfusion during operation.The urinary continence rates at the time of catheter removal,and at 1,3,and 6 months after surgery were 39.1%,65.2%,73.9%,and 91.3%,respectively.Two patients had positive margins,both of which were at the neurovascular bundle.No patient developed surgery-related complications,urinary obstruction or fistula after surgery.Conclusion Vesicourethral anastomosis with MULP and BNP in LRP for HRPC can effectively improve patients'early urinary continence rate and postoperative quality of life without increasing the oncological risk.
2.Analysis of NBI characteristics in recurrent laryngeal cancer patients after CO2 laser surgery under suspend laryngoscopy
Xiaohong LIU ; Ruixin GUO ; Meng XIE ; Yao SHI ; Nan CAO ; Xiaoyong REN ; Huanan LUO
Chinese Archives of Otolaryngology-Head and Neck Surgery 2024;31(7):409-413
OBJECTIVE To analyze the narrow-band imaging(NBI)endoscopic characteristics of recurrent early glottic carcinoma patients after undergoing CO2 laser surgery with a suspend laryngoscopy.METHODS A retrospective study was conducted on patients with early-stage glottic carcinoma(Ⅰ-Ⅱ stage)who received CO2 laser surgery under supportive laryngoscopy at the Department of Otolaryngology Head and Neck Surgery,the Second Affiliated Hospital of Xi'an Jiao Tong University from January 2017 to December 2023.The medical history,treatment methods,laryngoscopy(including common white light endoscopy and NBI endoscopy),imaging examinations,and pathological results of patients with recurrent glottic carcinoma were collected at different time points including preoperation,postoperative 1 month,postoperative 3 months,and postoperative 6 months.The endoscopic characteristics of NBI in patients with recurrent glottic carcinoma were summarized.RESULTS First,among 18 patients with early-stage glottic cancer recurrence after CO2 laser,the diagnostic rate of NBI endoscopy for laryngeal cancer recurrence(88.89%,16/18)was significantly higher than that of common white light endoscopy(55.56%,10/18)(χ2=4.985,P=0.026).The intraepithelial papillary capillary loop(IPCL)was classified as a vertical vessel according to ELS in all relapsed patients.However,according to Ni classification,the IPCL of the 72.22%(13/18)were classified as type V,while the IPCL of 27.78%(5/18)showed suspicious abnormal neovascularization(punctate or dilated and curved).The proportion of patients with abnormal IPCL on the surgical surface at 1 month,3 months,and 6 months postoperatively was 0.00%,27.78%(5/18),and 61.11%(11/18),respectively,with statistically significant differences(χ2=16.164,P<0.001),which indicated that the longer the follow-up time for recurrent laryngeal cancer patients,the higher the proportion of patients with abnormal IPCL on the surface of the surgical area under NBI endoscopy.CONCLUSION For early glottic carcinoma after CO2 laser surgery with a suspend laryngoscopy,the appearance of suspicious new blood vessels with type Ⅴ IPCL and punctate or dilated curvature under NBI endoscopy may indicate early recurrence of laryngeal cancer.
3.Analysis of the characteristics of temporary abnormal IPCL changes in the surgical area after CO2 laser resection for early glottic laryngeal cancer
Xiaohong LIU ; Meng XIE ; Yao SHI ; Nan CAO ; Haonan YANG ; Xiaoyong REN ; Huanan LUO
Chinese Archives of Otolaryngology-Head and Neck Surgery 2024;31(11):681-685
OBJECTIVE To analyze the changes of temporary abnormal intraepithelial papillary capillary loop(IPCL)in the surgical area of early glottic laryngeal cancer after CO2 laser resection.METHODS A retrospective study was conducted on early-stage glottic carcinoma patients who visited the Department of Otolaryngology,Head and Neck Surgery at the Second Affiliated Hospital from January 2017 to November 2023.Patients who underwent CO2 laser surgery accepted electronic laryngoscopy examination at 1 month,3 months,and 6 months postoperatively(including white light endoscopy and narrowband imaging endoscopy(NBI),and their medical history,treatment methods,laryngoscopy images,imaging data,and pathological results before and after treatment were systematically collected.The changes in laryngoscopy characteristics at different follow-up times after surgery were analyzed.RESULTS This study included 55 patients with non recurrent early glottic carcinoma who underwent CO2 laser surgery.At 1 month,3 months,and 6 months after surgery,there were significant differences in the proportion of patients with pseudomembrane coverage(72.73%vs.25.45%vs.7.27%),granulation formation(60.00%vs.34.55%vs.1.82%),and abnormal IPCL(23.64%vs.7.27%vs.0.00%)on the surface of the surgical area(P<0.001),and abnormal IPCL(mainly type Va and Vb)can be observed under NBI endoscopy from 1 month to 3 months after surgery.Within 6 months after surgery,the pseudomembrane detachment,granulation regression,scar formation,and abnormal IPCL in the surgical area disappeared.CONCLUSION Early glottic carcinoma patients may experience temporary abnormal IPCL within 3 months after receiving CO2 laser resection,but the abnormal IPCL could disappear within 6 months after surgery for some patients.Therefore,close observation is necessary within 6 months after surgery and there is no need for urgent biopsy.
4.Efficacy of different treatment duration of vonoprazan combined with low-dose amoxicillin in Helicobacter pylori eradication
Yizhou JIANG ; Kai MA ; Cheng CUI ; Xin CAO ; Xiaoyong WANG
Chinese Journal of Digestion 2024;44(6):361-367
Objective:To investigate the efficacy and safety of different treatment duration of dual therapy including vonoprazan and low-dose amoxicillin in Helicobacter pylori ( H. pylori) eradication. Methods:From December 1, 2022 to November 30, 2023, a total of 150 H. pylori-infected patients who underwent primary treatment in the Affiliated Changzhou No.2 People′s Hospital of Nanjing Medical University were recruited. The patients were divided into 10-day treatment group and 14-day treatment group with 75 patients in each group by random number table method. Patients of both groups were treated with vonoprazan (20 mg each time, twice per day) combined with amoxicillin (0.75 g each time, 3 times per day), and the treatment duration was 10 and 14 days, respectively. Intention-to-treat (ITT) and per-protocol (PP) analyses were used to evaluate the eradication efficacy of H. pylori of the 10-day treatment group and 14-day treatment group. PP analysis was used to compare the incidence of adverse events between the 2 groups. Cost-effectiveness analysis was performed to evaluate the economic efficiency of the 2 treatment regimens. Identified factors affecting the eradication rate in the 10-day treatment group based on the PP. Independent sample t-test and chi-square test were used for statistical analysis. Results:In ITT and PP analysis, a total of 75, 75 patients and 70, 72 patients were included in the 10-day treatment group and 14-day treatment group, respectively. The results of ITT analysis showed that the eradication rates of 10-day treatment group and 14-day treatment group were 86.7% (65/75) and 90.7% (68/75), respectively. The results of PP analysis showed that the eradication rates of the 2 groups were 92.9% (65/70) and 94.4% (68/72), respectively, and the differences were not statistically significant (both P>0.05). The results of PP analysis showed that the incidences of adverse events of the 10-day treatment group and 14-day treatment group were 12.9% (9/70) and 9.7% (7/72), respectively, and the difference was not statistically significant( P>0.05). The cost-effectiveness ratios of the 10-day treatment group and 14-day treatment group were 3.29 and 4.19 yuan/%, respectively. The optimal cut-off values were 63.5 kg for body weight and 1.73 m 2 for body surface area to affect the H. pylori eradication rate. The H. pylori eradication rate of patients with body weight ≤ 63.5 kg was higher than that of patients with body weight >63.5 kg (100.0%, 42/42 vs. 82.1%, 23/28), and the H. pylori eradication rate of the patients with body surface area≤1.73 m 2 was higher than that of patients with body surface area>1.73 m 2 (100.0%, 45/45 vs. 80.3%, 20/25), and the differences were statistically significant ( χ2=5.61 and 6.91, P=0.018 and 0.009). Conclusions:The 10-day combination therapy of vonoprazan and low-dose amoxicillin is a safe and effective primary treatment regimen for H. pylori eradication. Body weight and body surface area are influencing factors of the eradication rate.
5.Construction of OSA-related hypertension prediction model based on nomogram.
Yewen SHI ; Lina MA ; Simin ZHU ; Yanuo ZHOU ; Zine CAO ; Zitong WANG ; Yuqi YUAN ; Haiqin LIU ; Xiaoyong REN
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2024;38(11):1024-1037
Objective:This study aimed to construct a risk prediction model for obstructive sleep apnea(OSA) related hypertension based on the nomogram, and to explore the independent risk factors for OSA-related hypertension, so as to provide reference for clinical treatment decision-making. Methods:The clinical data of OSA patients diagnosed by polysomnography from October 2019 to December 2021 were collected retrospectively and randomly divided into training sets and validation sets. A total of 1 493 OSA patients with 27 variables were included. The least absolute shrinkage and selection operator(Lasso) logistic regression model was used to select potentially relevant features and establish a nomogram for OSA-related hypertension.The performance and clinical benefits of this nomogram were verified in terms of discrimination, calibration ability and clinical net benefit. Results:Multivariate logistic regression showed that body mass index(BMI), family history of hypertension, lowest oxygen saturation(LSaO2), age and cumulative percentage of total sleep time with oxygen saturation below 90% were independent risk factors for OSA-related hypertension. Lasso logistic regression identified BMI, family history of hypertension, LSaO2 and age as predictive factors for inclusion in the nomogram. The nomogram provided a favorable discrimination, with a C-indexes of 0.835(95% confidence interval[CI ]0.806-0.863) 0.865(95%CI 0.829-0.900) for the training and validation cohort, respectively, and well calibrated. The clinical decision curve analysis displayed that the nomogram was clinically useful. Conclusion:Compared with cumulative percentage of total sleep time with blood oxygen saturation below 90%, LSaO2 may have a greater impact on the incidence of OSA-related hypertension, and the effects of different times and degrees of hypoxia on OSA-related hypertension should be further explored in the future. Apnea hypopnea index involvement is weak in predicting OSA-related hypertension, and the blood oxygen index may be a better predictor variable. Furthermore, we established a risk prediction model for OSA-related hypertension patients using nomogram, and demonstrated that this prediction model was helpful to identify high-risk OSA-related hypertension patients. This model can provide early and individualized diagnosis and treatment plans, protect patients from the serious.
Humans
;
Sleep Apnea, Obstructive/complications*
;
Nomograms
;
Hypertension/epidemiology*
;
Male
;
Female
;
Risk Factors
;
Middle Aged
;
Retrospective Studies
;
Polysomnography
;
Logistic Models
;
Body Mass Index
;
Adult
6.Analysis of vocal characteristics in hypopharyngeal cancer patients with vocal cord dysfunction.
Xiaohong LIU ; Guoyuan MU ; Nan CAO ; Na LI ; Minjuan YANG ; Yangjuan CHEN ; Xiaoying DU ; Xiaoyong REN ; Huanan LUO
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2024;38(11):1056-1065
Objective:To analyze the acoustic characteristics of patients with hypopharyngeal cancer accompanied by vocal cord dysfunction. Methods:A retrospective analysis was conducted on the data of patients with hypopharyngeal cancer who were initially treated at The Second Affiliated Hospital of Xi'an Jiaotong University from January 2018 to April 2024. Patients who had completed electronic laryngoscopy, stroboscopic laryngoscopy, and voice analysis were selected from the data. Among them, patients with hypopharyngeal cancer who had unilateral vocal cord activity disorders were selected as the experimental group, while patients with symmetrical bilateral vocal cord activity were assigned to the control group. Then the clinical characteristics, the vocal parameters, and the stroboscopic laryngoscopy results of patients with hypopharyngeal cancer in the experimental group and the control group were analyzed and compared. Results:Compared with that in the control group, the proportion of lesions located on the inner wall of the piriform fossa in the experimental group increased(83.3% vs 53.8%), and the difference was statistically significant(P<0.05). There was no significant difference in vocal parameters such as SPL, Jitter, Shimmer, MPT, DSI, F0, sound intensity, electroglottic value and VHI between the experimental group and the control group(P>0.05). However, the values of F0, Jitter, Shimmer and VHI in the experimental group were higher than those in the control group. In addition, in terms of the results of stroboscopic laryngoscopy, the proportion of glottic insufficiency(42.9% vs 18.8%) and asymmetric arytenoid cartilage(64.3% vs 0) in the experimental group was significantly higher than that in the control group(P<0.05). However, the mucosal waves of the vocal cords on the affected side did not weaken in patients in both the experimental group and the control group. In the experimental group of 18 patients with hypopharyngeal cancer who received induction chemotherapy(nituzumab+nedaplatin+5-fluorouracil), 13 of them had improved vocal cord activity(improvement rate of 72.2%). Conclusion:Hypopharyngeal cancer in the medial wall of the pyriform fossa is more prone to vocal cord dysfunction, but vocal cord dysfunction has little effect on the vocal parameters of patients with hypopharyngeal cancer.
Humans
;
Hypopharyngeal Neoplasms
;
Retrospective Studies
;
Male
;
Female
;
Laryngoscopy
;
Middle Aged
;
Vocal Cord Dysfunction/etiology*
;
Vocal Cords/physiopathology*
;
Stroboscopy
;
Voice Quality
;
Aged
7.Establishment and evaluation of a risk prediction model for severe obstructive sleep apnea
Yewen SHI ; Yushan XIE ; Lina MA ; Zine CAO ; Yitong ZHANG ; Yonglong SU ; Xiaoxin NIU ; Haiqin LIU ; Yani FENG ; Xiaoyong REN
Journal of Xi'an Jiaotong University(Medical Sciences) 2023;44(6):915-923
【Objective】 To construct a prediction model of severe obstructive sleep apnea (OSA) risk in the general population by using nomogram in order to explore the independent risk factors of severe OSA and guide the early diagnosis and treatment. 【Methods】 We retrospectively enrolled patients who had been diagnosed by polysomnography and divided them into training and validation sets at the ratio of 7∶3. Patients were divided into severe OSA group and non-severe OSA group according to apnea hypopnea index (AHI)>30. Variables entering the model were identified by least absolute shrinkage and selection operator regression model (Lasso), and logistic regression (LR) method. Then, multivariable logistic regression analysis was used to establish the nomogram, and the area under the receiver operating characteristic curve (AUC) was used to evaluate the discriminative properties of the nomogram model. Finally, we conducted decision curve analysis (DCA) of nomogram model, STOP-Bang questionnaire and Berlin questionnaire to assess clinical utility. 【Results】 Through single factor and multiple factor logistic regression analyses, the independent risk factors for severe OSA were screened out, including moderate and severe sleepiness, family history of hypertension, history of smoking, drinking, snoring, history of suffocation, sedentary lifestyle, male, age, body mass index (BMI), waist and neck circumference. Lasso logistic regression identified smoke, suffocation time, snoring time, waistline, Epworth sleepiness scale (ESS) and BMI as predictive factors for inclusion in the nomogram. The AUC of the model was 0.795 [95% confidence interval (CI): 0.769-0.820] . Hosmer-Lemeshow test indicated that the model was well calibrated (χ2=3.942, P=0.862). The DCA results on the visual basis confirmed that the nomogram had superior overall net benefits within a wide, practical threshold probability range which displayed the nomogram was higher than that of STOP-Bang questionnaire and Berlin questionnaire, which is clinically useful. The Clinical Impact Curve (CIC) analysis showed the clinical effectiveness of the prediction model when the threshold probability was greater than 82% of the predicted score probability value. The prediction model determined that the high-risk population with severe OSA was highly matched with the actual population with severe OSA, which confirmed the high clinical effectiveness of the prediction model. 【Conclusion】 The model performed better than STOP-Bang questionnaire and Berlin questionnaire in predicting severe OSA and can be applied to screening. And it can be helpful to the early diagnosis and treatment of OSA in order to reduce social burden.
8.The efficacy of HoLEP with preservation of longitudinal urethral mucosa at 12 o’clock for benign prostatic hyperplasia with small-medium gland
Jianwen HUANG ; Zhiqiang LUO ; Nailong CAO ; Xiaoyong HU ; Jiong ZHANG ; Hui GUO ; Lujie SONG ; Qiang FU
Chinese Journal of Urology 2022;43(4):261-265
Objective:To explore the treatment experience of holmium laser enucleation of prostate (HoLEP) with preservation of longitudinal urethral mucosa at 12 o’clock for benign prostatic hyperplasia (BPH) with small-medium gland.Method:From October 2018 to April 2021, 256 patients diagnosed BPH with small-medium gland(prostate volume 30-60 ml)were retrospectively analyzed, including general information, way of operation, intraoperative parameters and follow-up data. From October 2018 to June 2020, 186 BPH patients underwent conventional HoLEP, which did not retain longitudinal urethral mucosa at 12 o’clock as a conventional operation group. From July 2020 to April 2021, 70 BPH patients underwent modified HoLEP, which retained longitudinal urethral mucosa at 12 o’clock as a modified operation group. There was no significant difference between the two groups( P>0.05) in term of the age[(70.5±4.4)years old vs.(68.5±3.2)years old], Q max[(7.5±2.8)ml/s vs.(7.5±2.1)ml/s], IPSS[(20.3±4.6)vs.(21.4±3.7)], QOL[(4.5±1.0)vs.(4.2±1.4)], postvoid residual volume[(126.9±29.36)ml vs.(132.2±32.3)ml], PSA[(1.5±1.3)ng/ml vs.(1.8±1.1)ng/ml] and prostate volume[(48.1±11.1)ml vs.(48.0±12.7)ml]. Both groups were treated with "trefoil" enucleation of prostate. The modified group was improved compared with the conventional group by retaining a 12 o’clock longitudinal urethra mucosa from the bladder neck to the apex of the prostate. The technical improvements were as follows: ①the left lobe of prostate was removed from at 5 o’clock at the verumontanum to 1 o’clock at the prostate apex along the gap between the hyperplasia gland and the surgical envelope; ②the right lobe was removed from 7 o’clock at the verumontanum to 11 o’clock at the apex; ③the urethra mucous membrane was cut vertically from 1 and 11 o’clock at the bladder neck to 1 and 11 o’clock at the apex respectively, and retaining the longitudinal mucous membrane between 11 and 1 o’clock (including 12 o’clock). Efficacy and postoperative complications of the two groups were compared. Results:The difference between the conventional group and the modified group in operation time[(36.5±10.4)min vs.(40.7±9.7)min], enucleated glandular weight[(35.5±12.2)g vs.(31.6±10.4)g], hemoglobin decline[(6.1±2.2)g/L vs.(5.6±2.5) g/L], postoperative hospitalization time [(1.2±0.2)d vs.(1.5±0.4)d]and catheter indwelling duration[(2.3±1.3)d vs.(2.0±1.0)d] were not statistically significant ( P>0.05). There were 252 patients for follow-up, including 183 cases in the conventional group and 69 cases in the modified group, and 4 cases were lost to follow-up. Mean time of follow-up was 8.4 months. In both groups, postoperative IPSS were 5.4±2.3 and 5.9±1.2 respectively, QOL1.5±0.3 and 2.0±1.0 respectively, Q max(24.3±9.2)ml/s and (22.5±11.3)ml/s respectively and postvoid residual volume (8.3±4.5)ml and (7.7±2.9)ml respectively, which were significantly different from that before the operation ( P<0.05). However, there was not significant difference between the two groups ( P>0.05). The postoperative immediate urinary continence rate of the conventional group and modified group were 85.2% (156/183), 98.6% (68/69), respectively, and two groups had statistical differences ( P<0.05). Incidence of postoperative bladder neck contraction were 4.4% (8/183) and 0 respectively in the conventional and modified group, whose difference was significant( P<0.05). Conclusions:HoLEP with preservation of longitudinal urethral mucosa at 12 o'clock is the same effective as conventional operation in the treatment of BPH with small-medium gland, likewise it could significantly improve immediate urinary continence rate and reduce the incidence of bladder neck contraction.
9.Treatment of benign prostate hyperplasia combined with mild urethra stenosis
Jianwen HUANG ; Zhiqiang LUO ; Nailong CAO ; Xiaoyong HU ; Jiong ZHANG ; Hui GUO ; Lujie SONG ; Qiang FU
Chinese Journal of Urology 2022;43(8):616-617
We retrospectively analyzed the clinical data of 21 patients diagnosed with BPH combined with mild urethra stenosis from January 2018 to December 2020. 12 patients underwent holmium laser enucleation of prostate (HoLEP). There were 3 cases of serious urethra stenosis requiring repeat surgical treatment after surgery, 9 cases of unobstructed voiding, 4 cases of reverse ejaculation and 2 cases of temporary urinary incontinence. 9 patients underwent laparoscopic simple prostatectomy (LSP) and all patients had unobstructed voiding. There were no cases of severe urethral stricture, temporary urinary incontinence and retrograde ejaculation in LSP group. LSP has reduced the risk of a repeat urethral surgery because of transurethral operation increasing the degree of urethra stenosis.
10.Scientific Characterization of Traditional Softening Method of Corydalis Rhizoma
Xinrui ZHANG ; Jing YANG ; Yao ZHANG ; Ailing ZHANG ; Hanfeng YUAN ; Zhongming CAO ; Xiaojian LUO ; Feng WANG ; Xiaoyong RAO
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(18):108-116
ObjectiveModern scientific methods and techniques were used to scientifically characterize the traditional softening process of Corydalis Rhizoma, so as to clarify the scientificity and rationality of the traditional process, and provide reference for inheriting the processing methods and experience of traditional Chinese medicine. MethodLow-field nuclear magnetic resonance imaging (LF-NMR/MRI) was used to characterize the water types and distribution in the softening process of Corydalis Rhizoma. Samples during the softening process was cut into thick slices and its section was observed by stereoscopic microscope. High performance liquid chromatography (HPLC) was employed to determine the content change of tetrahydropalmatine during the softening process with the mobile phase of methanol-0.1% phosphoric acid solution (60∶40, triethylamine regulated to pH 6.5) and detection wavelength at 280 nm. The determination method of softening endpoint of Corydalis Rhizoma was simulated by texture analyzer (hand pinch method), and the softening degree of the finished products was determined after optimizing the relevant parameters. ResultLF-NMR/MRI showed that the water could penetrate through the core and distribute evenly in Corydalis Rhizoma softened by Zhangbang method. The water first entered into the medicinal material from the epidermis and stem marks in the soaking stage as the form of free water, and then penetrated into the inner core to achieve redistribution in the moistening stage. Under stereoscopic microscope, it was observed that Corydalis Rhizoma softened by the Zhangbang method could be sliced well, but the core bursting slices were easy to appear if the softening time was not enough, and the softening of samples was caused by the keratine-like powder after absorbing water. HPLC measurement showed that the loss of tetrahydropalmatine in the softening method was small, its content decreased about 5% in the soaking process, and its content was almost unchanged during the moistening process. The softening degree of Corydalis Rhizoma could be quantified by the texture analyzer, and the optimum parameters were 2 mm·s-1 of speed before test, test speed and speed after test, 20 g of the trigger force, 20% of compression degree. The compressive force of the qualified softened Corydalis Rhizoma was 12.75-15.69 N with the relative standard deviation (RSD) of 6.8%. ConclusionModern scientific methods and techniques can characterize the scientificity and rationality of the traditional processing methods, and confirm that the Zhangbang softening method has the advantages of high efficiency, convenience and small loss of index components. The texture analyzer can simulate the softening endpoint judgment method (hand pinch method), and realize the goal from subjective experience judgment to objective technology quantification, which has a good demonstration role for the modern inheritance of traditional processing technology.

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