1.Influencing factors of bladder management practices in patients with spinal cord injury
Zhirong LUO ; Xuyan GUO ; Qi XUE ; Xiao TAN ; Yunhua JI ; Fuxun ZHANG ; Yong JIAO ; Bo ZHANG
Journal of Modern Urology 2025;30(4):284-289
Objective: To explore the key factors affecting the selection and effectiveness of bladder management modalities in patients with spinal cord injury,so as to provide reference for the optimization of individualized bladder management strategies. Methods: The clinical and follow-up data of 78 patients with spinal cord injury treated in our hospital during Jan.1,2013 and Dec.31,2022 were retrospectively analyzed.The distribution of bladder management modalities among different grades of injuries was analyzed. Bowker symmetry test was used to evaluate the difference between bladder management modalities at discharge and at the end of follow-up. Multiple linear regression was used to explore the influencing factors of bladder management effects. Plotting Kaplan-Meier survival curves were adopted to calculate the median time of changes in bladder management. Results: At discharge,there were 9 cases of self-catheterization,19 cases of intermittent catheterization,22 cases of reflexive voiding,26 cases of long-term catheterization,and 2 cases using urinary collector.At the end of follow-up,there were 15 cases of self-catheterization,8 cases of intermittent catheterization,34 cases of reflexive voiding,14 cases of long-term catheterization,and 7 cases using urinary collector.There was a significant difference between the modalities of bladder management at discharge and at the end of follow-up (χ
=21.43,P=0.018).Multiple linear regression showed a significant decrease of 8.60 in the total neurogenic bladder symptom score (NBSS) for grade D injuries compared with grade A injuries (P=0.026). The median time to bladder management change was 7.93 months (95%CI:5.44-9.44), with approximately 50% of patients experiencing a change in bladder management within 8 months after discharge. Conclusion: The modalities of bladder management changed significantly after discharge.The grade of injury was a key factor affecting the effectiveness of bladder management.Higher grade was associated with worse effectiveness of bladder management.
2.Analysis of the causal relationship between gut microbiota and bladder cancer with Mendelian randomization
Xuyan GUO ; Zhirong LUO ; Qi XUE ; Yunhua JI ; Xiao TAN ; Yong JIAO
Journal of Modern Urology 2025;30(5):400-407
Objective: Previous observational studies have confirmed the correlation between gut microbiota and bladder cancer,but the causal relationship is still unclear.This study aimed to explore the causal relationship between them with Mendelian randomization. Methods: Genetic variation summary data of 211 gut microbiota and bladder cancer genome-wide association studies (GWAS) were obtained from the MiBioGen Consortium and Finngen database.Single nucleotide polymorphisms (SNPs) closely related to these studies were screened as instrumental variables.The causal relationship between gut microbiota and bladder cancer were analyzed with inverse variance weighting (IVW),MR-Egger,weighted median,maximum likelihood,robust adjustment feature score and MR-PRESSO,with IVW as the primary analysis method.Additionally,sensitivity analysis was used to test the heterogeneity (Cochran Q) and horizontal pleiotropy (MR-Egger intercept term and global test from MR-PRESSO estimator) to ensure the robustness of the results. Results: The IVW results indicated that Lachnospiraceae UCG004 (OR:1.42),Desulfovibrionales (Order) (OR:1.48),Eubacterium ruminantium group (OR:1.33),Olsenella (OR:1.24),Ruminococcaceae UCG002 (OR:1.39),Ruminococcaceae UCG005 (OR:1.42) and Ruminococcaceae UCG013 (OR:1.64) significantly increased the risk of bladder cancer.Conversely,Bacteroidetes (Phylum) (OR:0.61),Eubacterium brachy group (OR:0.80),Ruminococcaceae UCG004 (OR:0.73),Rikenellaceae (Family) (OR:0.67),Lachnospiraceae ND3007 group (OR:0.47), Adlercreutzia (OR:0.73) and an unknow genus (OR:0.75) were associated with a reduced risk of bladder cancer.Sensitivity analyses did not reveal any heterogeneity or horizontal pleiotropy. Conclusion: This study reveals the causal role of 14 gut microbiota in the pathogenesis of bladder cancer,among which Lachnospiraceae UCG004,Desulfovibrionales (Order),Eubacterium ruminantium group,Olsenella,Ruminococcaceae UCG002,Ruminococcaceae UCG005 and Ruminococcaceae UCG013 are risk factors for bladder cancer,while Bacteroidetes (Phylum),Eubacterium brachy group,Ruminococcaceae UCG004,Rikenellaceae (Family),Lachnospiraceae ND3007 group,Adlercreutzia and an unknown genus are the protective factors.
3.Comparison of the effects of transperineal prostate laser ablation versus transurethral resection of the prostate in the treatment of benign prostatic hyperplasia:a single center prospective randomized controlled study
Zhen YAO ; Yunhua JI ; Linmeng WANG ; Qi XUE ; Manman SHI ; Zhirong LUO ; Bo ZHANG
Journal of Modern Urology 2024;29(6):486-491
Objective To compare the clinical efficacy of transperineal prostate laser ablation(TPLA)and transurethral resection of the prostate(TURP)in the treatment of benign prostatic hyperplasia(BPH).Methods A total of 60 BPH patients diagnosed during Oct.2021 and Oct.2022 at Tangdu Hospital were selected as the research subjects and randomly divided into the TPLA group(n=30)and TURP group(n=30).The intraoperative bleeding volume,operation time,catheter indwelling time,length of hospital stay,postoperative sexual dysfunction,and surgical related complications were compared between the two groups.The international prostate symptom score(IPSS),international index of erectile function-5(IIEF-5),maximum urinary flow rate(Qmax),quality of life score(QoL),postvoid residual(PVR)and prostate volume(PV)were compared between the two groups before surgery and 1,3,and 12 months after surgery.Results The TPLA group had significantly less intraoperative bleeding volume,shorter operation time and length of hospital stay compared to the TURP group,but longer catheter indwelling time(P<0.05).Both groups showed significant improvement in IPSS and Qmax 1,3,and 12 months postoperatively compared to preoperative(P<0.05),the IPSS of the TPLA group was significantly higher than that of the TURP group 1 and 3 months after surgery(P<0.05);the Qmax of TPLA group 1,3,and 12 months after surgery was lower than that of the TURP group(P<0.05).The IIEF-5 score was significantly better in the TPLA group than in the TURP group after surgery(P<0.05).The postoperative QoL,PV,and PVR levels in both groups improved after surgery(P<0.05),the QoL of the TPLA group was lower than that of the TURP group 1 and 12 months after surgery(P<0.05),the PV and PVR of the TPLA group were higher than those of the TURP group 1,3,and 12 months after surgery(P<0.05).The incidence of surgery-related complications(3.33%vs.26.67%)and postoperative sexual dysfunction(3.33%vs.36.67%)in the TPLA group were lower than those in the TURP group(P<0.05).Conclusion TPLA shows significant efficacy in treating BPH with minimal impact on the sexual function.It provides a new approach for BPH patients and can serve as an effective complementary method in clinical practice.
4.The hemodynamic effects of ductus arteriosus on modified Blalock-Taussig shunt
Jiwen XIONG ; Qi SUN ; Jinfen LIU ; Liwei HU ; Zhirong TONG ; Jinlong LIU
Chinese Journal of Thoracic and Cardiovascular Surgery 2021;37(3):154-158
Objective:To investigate hemodynamic characteristics of the modified Blalock-Taussig shunt (MBTS) with the preservation or ligation of ductus arteriosus (DA) based on computational fluid dynamics (CFD), thus to help preoperative surgery design and postoperative prediction.Methods:A patient with pulmonary atresia and patent ductus arteriosus was included. Patient-specific three-dimensional model was reconstructed and virtual surgeries of shunt insertion and ductus ligation or preservation were performed via computer-aided design (CAD). CFD was utilized to analyze hemodynamic parameters preoperatively and postoperatively based on patient-specific anatomy and physiologic data.Results:The preservation of DA competitively reduced the shunt flow but increased total pulmonary perfusion. The shunt flow and ductal flow collided with each other, causing large and complicated turbulence in pulmonary artery where lower wall shear stress and higher oscillatory shear index were distributed, as well as higher energy loss.Conclusion:The preservation of DA is riskier in hemodynamics which may lead to pulmonary over-perfusion, inadequate systemic perfusion and heavier cardiac burden, thus increasing the risk of heart failure and it seems to bring no benefit in terms of reducing risks of thrombosis.
5.Effects of “Sweat Soaking Method ”on the Content of Genkwanin in Wikstroemia indica and Its Anti-oxidation Ability
Zhirong ZHOU ; Guo FENG ; Wei LI ; Qi Chuan ZHENG ; Qin XU ; Chenchen REN ; Lizhen PENG ; Qiaozong HUANG ; Xiaoyan XIAO
China Pharmacy 2020;31(19):2320-2325
OBJECTIVE:To compare the content changes of active/toxic ingredient genkwanin in ethanol extract from Wikstroemia indica before and after processing with “sweat soaking method ”and the effects of processing method on its anti-oxidation ability. METHODS :HPLC method was adopted to determine the content of genkwanin in W. indica before and after processing with “sweat soaking method ”. The separation was performed on Diamonsil C 18 column with 0.2% phosphoric acid solution-methanol as mobile phase (gradient elution )at the flow rate of 1 mL/min. The column temperature was 30 ℃ and detection wavelength was set at 346 nm. The sample size was 20 µL. SD rats were randomly divided into blank group ,W. indica raw product ethanol extract group (317.52 mg/kg,called“raw-product group ”as short )and W. indica processed product ethanol extract group (317.52 mg/kg,called“processed-product group ”as short ),with 6 rats in each group. Blank group was given constant volume of 1.0%CMC-Na solution intragastrically ,and administration groups were given relevant medicine suspension intragastrically;all of them were given 20 mL/kg,once a day ,for consecutive 14 days. The contents of serum oxidant stress indexes(MDA,CAT,SOD)in rats were determined by ELISA. RESULTS :The linear range of genkwanin were 0.147-27.360 μg (r=0.999 9);RSDs of precision ,reproducibility and stability tests were all lower than 3% ;average recoveries were 98.64%-98.92%(RSD<1%,n=3). Before and after processing with “sweat soaking method ”,average contents of genkwanin in W. indica were 0.377 6 and 0.234 0 mg/g. Compared with blank group ,the serum content of SOD in raw-product group was increased significantly ,while CAT content was decreased significantly (P<0.05 or P<0.01);the serum content of MDA was decreased significantly in processed-product group ,while SOD content was increased significantly (P<0.05 or P<0.01). MDA content of processed-product group was significantly lower than that of raw-product group ,while SOD content was significantly higher than raw-product group (P<0.05). CONCLUSIONS :After proce ssing with “sweat soaking method ”,the content of genkwanin in W. indica is decreased ,and antioxidant activity is increased .“Sweat soaking method ”processes certain function of “reducing toxicity and increasing efficiency ”.
6.Analysis of the clinical characteristics and related background diseases of 134 type 1 gastric neuroendocrine tumor
Yixuan ZHANG ; Yingying CHEN ; Zhirong QI ; Luohai CHEN ; Jie LUO ; Yuan LIN ; Jixi LIU ; Huangying TAN ; Jie CHEN
Chinese Journal of Digestion 2019;39(8):539-544
Objective To explore the clinical characteristics and related background diseases of type 1 gastric neuroendocrine tumor (g-NET) and to provide reference information for clinical diagnosis and treatment.Methods From Januayy 2011 to February 2019,at the First Affiliated Hospital of Sun Yat-sen University and China-Japan Friendship Hospital,the clinical features and related background diseases of type 1 g-NET patients (41 cases and 93 cases respectively)were retrospectively analyzed.The clinical symptoms,serological indicators,gastroscopic and pathological features,tumor location,metastasis and treatment,and concomitant diseases were statistically described.Results Among 134 patients with type 1 g-NET,there were 53 males (39.6%) and 81 females (60.4 %);and the mean diagnosed age was (51 ± 11) years (21 to 76 years).Main clinical manifestations were non-specific gastrointestinal symptoms.The mean level of serum chromogranin A was (237.7 ± 176.8) μg/L.The endoscopic findings of 97.8% (131/134) of the patients were polypoid or protuberant lesions at gastric fundus or gastric body.And 75.0% (96/128) of the patients had multiple tumors.65.7% (88/134) of the patients had the tumors with the maximum diameter less than 1 cm (77.2%,88/114) and the lesions mainly located in mucosa (59.8%,52/87) and submucosa (40.2%,35/87).The pathological classification of 79.3% (96/121) of the tumors was G1 grade and 20.7% (25/121) were G2 grade.The rate of local lymph node metastasis was 1.4% (1/73) and no distant metastasis was found.About 70.9% (95/134) of the patients received endoscopic treatment.Among the patients,93.6% (103/110) of the patients had chronic atrophic gastritis confirmed by endoscopy or pathology,45.6% (47/103) were confirmed by both endoscopy and pathology.Among the patients with chronic atrophy gastritis,serum gastrin levels of 93.2% (96/103) patients were twice higher than the upper limit of the normal value.The positive rates of antiparietal cells antibody (PCA) and intrinsic factor (IFA) were 78.5% (73/93) and 51.9% (14/27),respectively.The incidence of Helicobacter pylori (H.pylori) infection was 28.1% (16/57).The incidence of autoimmune atrophy gastritis was 80.6% (75/93).The percentage of patients with deficiency of serum vitamin B12 and ferritin was 70.8% (63/89) and 30.7% (27/88),respectively.Patients with anemia accounted for 27.8% (25/90).The patients with microcytic anemia,normocyticanemia and macrocytic anemia were 28.0% (7/25),56.0% (14/25) and 16.0% (4/25),respectively.46.9% (45/96) of the patients had increased thyroid autoantibodies and 17.9% (17/95) patients had changes of thyroid hormone level.Conclusions Type 1 g-NET is more common in women and mainly caused by autoimmune atrophic gastritis.The level of serum PCA and IFA increase in more than half of the patients.And it is often accompanied by vitamin B12 deficiency and autoimmune thyroid disease.
7.Survival after surgical treatment of bilateral synchronous multiple primary non-small cell lung cancers
Zhirong ZHANG ; Yousheng MAO ; Shugeng GAO ; Juwei MU ; Qi XUE ; Dali WANG ; Yushun GAO ; Jun ZHAO ; Jie HE
Chinese Journal of Oncology 2016;38(6):460-465
Objective To explore the clinical characteristics of patients with bilateral synchronous multiple primary non?small cell lung cancer ( NSCLC) and identify the prognostic indicators associated with survival. Methods From January 2010 to December 2014, clinicopathological data of 96 patients with bilateral synchronous multiple primary NSCLC, who met the modified Martini?Melamed criteria and underwent radical surgical resection, were retrospectively reviewed. Survival was estimated using the Kaplan?Meier method, and the clinical parameters associated with survival were analyzed using a log?rank test. Cox proportional hazards regression models were used to identify the risk factors for this cancer. Results Of the 96 patients, two patients who died of severe postoperative complications were excluded, and 94 patients were analyzed. Of the 94 cases, a two?stage operation was performed in 93 patients, while a single?stage bilateral surgery was performed in only one patient using video?assisted thoracic surgery ( VATS) . 79 patients had 2 tumors and the other 15 patients had 3 or more tumors. There were 82 patients with synchronous tumors located in different lobes and 12 patients had at least two tumors located in the same lobe. Seventy?six patients were found to have multiple lung adenocarcinoma and 12 patients had multiple squamous cell
carcinoma ( SCCs) . Five patients had adenocarcinoma and SCC, and one patient had adenocarcinoma and adenosquamous carcinoma simultaneously. Univariate analysis showed that the large maximum tumor diameter, highest pT stage and lymph node involvement were associated with an unfavorable DFS ( P<0.01 for all ) , while female gender, small maximum tumor diameter, early highest pT stage and pN0 were associated with a better overall survival ( OS) . Multivariate analysis showed that highest pT stage and lymph node metastasis were independent prognostic factors for DFS and OS. Patients with a lower highest pT stage and negative lymph node metastasis had longer DFS and OS ( P<0. 05 for both ) . Conclusions The diagnosis for patients with bilateral synchronous multiple primary NSCLCs should be made very carefully. Two stage surgical treatment is safe, reasonable and effective for patients with bilateral synchronous multiple primary NSCLCs in a relatively early stage. The highest pT stage and pN status are important predictors for long?term survival. Adequate pulmonary tissue resection with complete resection of multiple nodules and systematic lymphadenectomy are suggested.
8.Survival after surgical treatment of bilateral synchronous multiple primary non-small cell lung cancers
Zhirong ZHANG ; Yousheng MAO ; Shugeng GAO ; Juwei MU ; Qi XUE ; Dali WANG ; Yushun GAO ; Jun ZHAO ; Jie HE
Chinese Journal of Oncology 2016;38(6):460-465
Objective To explore the clinical characteristics of patients with bilateral synchronous multiple primary non?small cell lung cancer ( NSCLC) and identify the prognostic indicators associated with survival. Methods From January 2010 to December 2014, clinicopathological data of 96 patients with bilateral synchronous multiple primary NSCLC, who met the modified Martini?Melamed criteria and underwent radical surgical resection, were retrospectively reviewed. Survival was estimated using the Kaplan?Meier method, and the clinical parameters associated with survival were analyzed using a log?rank test. Cox proportional hazards regression models were used to identify the risk factors for this cancer. Results Of the 96 patients, two patients who died of severe postoperative complications were excluded, and 94 patients were analyzed. Of the 94 cases, a two?stage operation was performed in 93 patients, while a single?stage bilateral surgery was performed in only one patient using video?assisted thoracic surgery ( VATS) . 79 patients had 2 tumors and the other 15 patients had 3 or more tumors. There were 82 patients with synchronous tumors located in different lobes and 12 patients had at least two tumors located in the same lobe. Seventy?six patients were found to have multiple lung adenocarcinoma and 12 patients had multiple squamous cell
carcinoma ( SCCs) . Five patients had adenocarcinoma and SCC, and one patient had adenocarcinoma and adenosquamous carcinoma simultaneously. Univariate analysis showed that the large maximum tumor diameter, highest pT stage and lymph node involvement were associated with an unfavorable DFS ( P<0.01 for all ) , while female gender, small maximum tumor diameter, early highest pT stage and pN0 were associated with a better overall survival ( OS) . Multivariate analysis showed that highest pT stage and lymph node metastasis were independent prognostic factors for DFS and OS. Patients with a lower highest pT stage and negative lymph node metastasis had longer DFS and OS ( P<0. 05 for both ) . Conclusions The diagnosis for patients with bilateral synchronous multiple primary NSCLCs should be made very carefully. Two stage surgical treatment is safe, reasonable and effective for patients with bilateral synchronous multiple primary NSCLCs in a relatively early stage. The highest pT stage and pN status are important predictors for long?term survival. Adequate pulmonary tissue resection with complete resection of multiple nodules and systematic lymphadenectomy are suggested.
9.Comparison of the lymph node dissection and complications between video-assisted thoracoscopic (VATS) esophagectomy and conventional esophagectomy via right thoracotomic.
Yousheng MAO ; Jie HE ; Email: PROF.HEJIE@263.NET. ; Zhirong ZHANG ; Jingsi DONG ; Shugeng GAO ; Kelin SUN ; Guiyu CHENG ; Juwei MU ; Qi XUE ; Xiangyang LIU ; Dekang FANG ; Dali WANG ; Jun ZHAO ; Jian LI ; Yonggang WANG ; Yushun GAO ; Jinfeng HUANG
Chinese Journal of Oncology 2015;37(7):530-533
OBJECTIVEVideo-assisted thoracoscopic (VATS) esophagectomy has been performed for more than 10 years in China. However, compared with the conventional esophagectomy via right thoracotomy, whether VATS esophagectomy has more advantages or not in the lymph node (LN) dissection and prevention of perioperative complications is still controversial and deserves to be further investigated. The aim of this study was to explore whether there are significant differences in this issue between the two surgical modalities or not.
METHODSThe results of lymph node dissection and perioperative complications as well as other parameters in the patients treated by VATS esophagectomy and those by conventional esophagectomy via right thoracotomy at our department from May 1, 2009 to July 30, 2013 were compared using SPSS 16.0 in order to investigate whether there was any significant difference between these two treatment modalities in the learning curve stage of VATS esophagectomy.
RESULTSOne hundred and twenty-nine cases underwent VATS esophagectomy between May 1, 2009 and July 30, 2013, and another part 129 cases with the same preoperative cTNM stage treated by conventional esopahgectomy via right thoracotomy were selected in order to compare the results of lymph node dissection and perioperative complications as well as other parameters between those two groups of patients. There were no significant differences in the sex, age, lesion locations and cTNM stage between these two groups. The total LN metastatic rate in the VATS esophagectomy group was 35.7% and that of the conventional esophagectomy group was 37.2% (P > 0.05). The total average number of dissected lymph nodes was 12.1 vs. 16.2 (P < 0.001). The average dissected LN stations was 3.2 vs. 3.6 (P = 0.038). The total average number of dissected LN along the left recurrent laryngeal nerve was 2.0 vs. 3.7 (P = 0.012). The total average number of dissected LN along the right recurrent laryngeal nerve was 2.9 vs. 3.4 (P = 0.231). However, there was no significant difference in the total average number of dissected LN in the other thoracic LN stations, and in the perioperative complications between the two groups. The total postoperative complication rate was 41.1% in the VATS group versus 42.6% in the conventional group (P = 0.801). The cardiopulmonary complication rate was 25.6% vs. 27.1% (P = 0.777). The death rate was the same in the two groups (0.8%). The VATS group had less blood infusion (23.2% vs. 41.8%, P = 0.001) and shorter hospital stay (15.9 days vs. 19.2 days, P = 0.049) but longer operating time (161.3 min vs. 127.8 min, P < 0.01).
CONCLUSIONSIn the learning curve stage of VATS esophagectomy, compared with the conventional esophagectomy, less LN number and stations can be dissected in the VATS group due to un-skillful VATS manipulation, especially it is more difficult in the LN dissection along the left recurrent laryngeal nerve. Therefore, it is more suitable to select patients with early esophageal cancer without obvious enlarged lymph nodes for VATS esophagectomy in the learning curve stage.
China ; Esophageal Neoplasms ; pathology ; surgery ; Esophagectomy ; adverse effects ; methods ; Humans ; Learning Curve ; Length of Stay ; Lymph Node Excision ; adverse effects ; methods ; statistics & numerical data ; Lymph Nodes ; Operative Time ; Postoperative Complications ; epidemiology ; Recurrent Laryngeal Nerve ; Thoracic Surgery, Video-Assisted ; adverse effects ; Thoracotomy
10.Prevalence of atopic dermatitis, ichthyosis and filaggrin mutations in adolescents in a middle school in Shanghai
Qiufang QIAN ; Ruhong CHENG ; Ming LI ; Yifeng GUO ; Xia YU ; Zhen ZHANG ; Hong YU ; Huaishan QI ; Zhirong YAO
Chinese Journal of Dermatology 2015;(9):629-632
Objective To investigate the prevalence and progression process of atopic diseases in adolescents, and to assess their relationship with filaggrin(FLG)mutations. Methods Totally, 334 adolescents aged from 11 to 19 years in a middle school in shanghai were enrolled into this study. A clinical interview was carried out to determine the prevalence of atopic diseases (such as ichthyosis, atopic dermatitis (AD), asthma, rhinitis, etc)in these subjects. Peripheral blood samples were collected from 285 out of the 334 adolescents for screening for common FLG mutations, including 3321delA and K4671X. Five years later, these adolescents were followed up for reevaluation of clinical presentations of atopic diseases. Statistical analysis was carried out by the chi-square test with the SPSS 20.0 software. Results As the baseline survey showed, 19 (5.69%)of the 334 adolescents had AD, 14 (4.19%)had ichthyosis vulgaris, 36(10.78%)had allergic rhinitis, and 4(1.20%)had asthma. FLG mutations were observed in 24(8.42%) of the 285 adolescents. Five years later, 265 adoscents completed the follow-up, and 69 (20.66%)were lost to follow-up. Of the 265 adolescents reevaluated, 13(4.89%)had AD, 15(5.64%)had ichthyosis vulgaris, 27(10.15%)had allergic rhinitis, and 1 (0.38%)had asthma. By the time the second survey was performed, 6 out of the 19 patients initially diagnosed with AD had achieved complete regression, 13 had experienced a marked decrease in SCORing atopic dermatitis (SCORAD)score, and symptoms had disappeared in 9 of the 36 patients initially diagnosed with allergic rhinitis. The frequency of FLG mutations was 10.0%in patients with AD, 55.6%in those with ichthyosis, and 40.0%in those with both AD and ichthyosis, and the development of ichthyosis was associated with FLG mutations(P<0.001). Conclusions The frequency of common FLG mutations was 8.42%in these adolescents. FLG gene may be a semidominant gene associated with ichthyosis vulgaris, and multiple factors influence its expression.

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