1.Functionalized Cadmium-Metal Organic Framework Materials with Azo Bonds for Highly Sensitive Electrochemical Detection of 4-Aminophenol
Lu XU ; Tian-Tian MA ; Yi-Yan BAI ; Jing SU ; Yun-Long FU ; Hai-Ying YANG ; Wen-Juan JI
Chinese Journal of Analytical Chemistry 2024;52(4):587-596
The presence of 4-aminophenol(4-AP)in wastewater from the pharmaceutical industry is a common occurrence due to its role as a byproduct or intermediate during the hydrolysis process of paracetamol metabolism,resulting in significant water pollution.Therefore,it is crucial to employ a straightforward and reliable analytical approach for detecting 4-AP in the environment.In this study,a specific type of metal-organic framework(MOF)material called[Cd4(ABTC)2(H2O)12]n(SXNU-4-Cd,H4ABTC=3,3′,5,5′-azobenzene tetracarboxylic acid)was successfully synthesized,which exhibited a unique two-dimensional layered structure consisting of three intertwined spiral chains forming a distinctive″twist braid″.These layers underwent π-π stacking,creating three-dimensional channels with azo bonds decorating the channel walls.This p-π interaction significantly enhanced the adsorption capacity of SXNU-4-Cd towards 4-AP,thereby improving its recognition sensitivity.The fabricated SXNU-4-Cd/GCE sensor showed high sensitivity towards 4-AP in the linear concentration range of 0.1-130 μmol/L,with a detection limit of 8.6 nmol/L,and also exhibited good anti-interference capability,reproducibility and stability.The SXNU-4-Cd/GCE sensor was successfully used for detecting 4-AP in lake water sample,with spiked recoveries of 95.9%-102.8%.This study introduced a novel technique that utilized pure Cd-MOFs to develop electrochemical sensor capable of effectively detecting 4-AP in water samples.
2.Quality standard for Zhujieshen Formula Granules based on standard decoction
Chen-Hui YE ; Hai-Ming TANG ; Cheng-Fu YUAN ; Jia-Long GUO ; Ji-Hong ZHANG ; Ding YUAN ; Yu-Min HE
Chinese Traditional Patent Medicine 2024;46(9):2863-2869
AIM To establish the quality standard of the zhujieshen Formula Granules based on standard decoction.METHODS The contents and transfer rates of ginsenoside Ro and chikusetsu saponin Ⅳa in standard decoction and formula granules were determined by HPLC,after which the transfer rates were calculated.The HPLC characteristic chromatograms of standard decoctions were established,after which cluster analysis and principal component analysis were adopted.Then the HPLC characteristic chromatograms of formula granules were established.RESULTS Nine common peaks were found in the HPLC characteristic chromatograms of seventeen batches of standard decoctions with the similarities of more than 0.9(except for S6,S12),which were clustered into two categories,and the accumulative variance contribution rate of three principal components reached 86.7%.The contents of ginsenoside Ro in three batches of formula granules were 83.1-88.6 mg/g,and the transfer rates were 53.1%-55.5%.The contents of chikusetsusaponin Ⅳa were 14.8-15.0 mg/g,and the transfer rates were 47.4%-48.1%.Nine common peaks were found in the HPLC characteristic chromatograms of three batches of formula granules with the similarities of 0.998,0.998 and 0.999,respectively.CONCLUSION This reasonable and reliable method can comprehensively evaluate the quality of Zhujieshen Formula Granules,and provide a reference for the quality control.
3.Free PSA performs better than total PSA in predicting prostate volume in Chinese men with PSA levels of 2.5-9.9 ng ml-1.
Ma-Ping HUANG ; Ping TANG ; Cliff S KLEIN ; Xing-Hua WEI ; Wei DU ; Jin-Gao FU ; Tian-Hai HUANG ; Hui CHEN ; Ke-Ji XIE
Asian Journal of Andrology 2023;25(1):82-85
This study investigated whether free prostate-specific antigen (fPSA) performs better than total PSA (tPSA) in predicting prostate volume (PV) in Chinese men with different PSA levels. A total of 5463 men with PSA levels of <10 ng ml-1 and without prostate cancer diagnosis were included in this study. Patients were classified into four groups: PSA <2.5 ng ml-1, 2.5-3.9 ng ml-1, 4.0-9.9 ng ml-1, and 2.5-9.9 ng ml-1. Pearson/Spearman's correlation coefficient (r) and receiver operating characteristic (ROC) curves were used to evaluate the ability of tPSA and fPSA to predict PV. The correlation coefficient between tPSA and PV in the PSA <2.5 ng ml-1 cohort (r = 0.422; P < 0.001) was markedly higher than those of the cohorts with PSA levels of 2.5-3.9 ng ml-1, 4.0-9.9 ng ml-1, and 2.5-9.9 ng ml-1 (r = 0.114, 0.167, and 0.264, respectively; all P ≤ 0.001), while fPSA levels did not differ significantly among different PSA groups. Area under ROC curve (AUC) analyses revealed that the performance of fPSA in predicting PV ≥40 ml (AUC: 0.694, 0.714, and 0.727) was better than that of tPSA (AUC = 0.545, 0.561, and 0.611) in men with PSA levels of 2.5-3.9 ng ml-1, 4.0-9.9 ng ml-1, and 2.5-9.9 ng ml-1, respectively, but not at PSA levels of <2.5 ng ml-1 (AUC: 0.713 vs 0.720). These findings suggest that the relationship between tPSA and PV may vary with PSA level and that fPSA is more powerful at predicting PV only in the ''gray zone'' (PSA levels of 2.5-9.9 ng ml-1), but its performance was similar to that of tPSA at PSA levels of <2.5 ng ml-1.
Male
;
Humans
;
Prostate-Specific Antigen
;
Prostate
;
East Asian People
;
Prostatic Neoplasms/diagnosis*
;
ROC Curve
4.Establishment and validation of a nomogram-based predictive model for idiopathic aldosteronism.
Juan FEI ; Hang SHEN ; Shu Min YANG ; Zhi Peng DU ; Jin Bo HU ; Hai Bin WANG ; Gui Jun QIN ; Hong Fei JI ; Qi Fu LI ; Ying SONG
Chinese Journal of Internal Medicine 2023;62(6):693-699
Objective: To establish and validate a nomogram-based predictive model for idiopathic hyperaldosteronism (IHA). Methods: This cross-sectional study was conducted with the collected clinical and biochemical data of patients with primary aldosteronism (PA) including 249 patients with unilateral primary aldosteronism (UPA) and 107 patients with IHA, who were treated at the Department of Endocrinology of the First Affiliated Hospital of Chongqing Medical University from November 2013 to November 2022. Plasma aldosterone concentration (PAC) and plasma renin concentration (PRC) were measured by chemiluminescence. Stepwise regression analysis was applied to select the key predictors of IHA, and a nomogram-based scoring model was developed. The model was validated in another external independent cohort of patients with PA including 62 patients with UPA and 43 patients with IHA, who were diagnosed at the Department of Endocrinology, First Affiliated Hospital of Zhengzhou University. An independent-sample t test, Mann-Whitney U test, and χ2 test were used for statistical analysis. Results: In the training cohort, in comparison with the UPA group, the IHA group showed a higher serum potassium level [M(Q1, Q3), 3.4 (3.1, 3.8) mmol/L vs. 2.7 (2.1, 3.1) mmol/L] and higher PRC [4.0 (2.1, 8.2) mU/L vs. 1.5 (0.6, 3.4) mU/L] and a lower PAC post-saline infusion test (SIT) [305 (222, 416) pmol/L vs. 720 (443, 1 136) pmol/L] and a lower rate of unilateral adrenal nodules [33.6% (36/107) vs. 81.1% (202/249)]; the intergroup differences in these measurements were statistically significant (all P<0.001). Serum potassium level, PRC, PAC post-SIT, and the rate of unilateral adrenal nodules showed similar performance in the IHA group in the validation cohort. After stepwise regression analysis for all significant variables in the training cohort, a scoring model based on a nomogram was constructed, and the predictive parameters included the rate of unilateral adrenal nodules, serum potassium concentration, PAC post-SIT, and PRC in the standing position. When the total score was ≥14, the model showed a sensitivity of 0.65 and specificity of 0.90 in the training cohort and a sensitivity of 0.56 and specificity of 1.00 in the validation cohort. Conclusion: The nomogram was used to successfully develop a model for prediction of IHA that could facilitate selection of patients with IHA who required medication directly.
Humans
;
Hyperaldosteronism/diagnosis*
;
Nomograms
;
Hypertension
;
Cross-Sectional Studies
;
Aldosterone
;
Saline Solution
;
Renin
;
Potassium
5.Research progress on organ protective effects and mechanisms of dexmedetomidine
Yun-Ying DING ; Fu-Hai JI ; Ke PENG
Medical Journal of Chinese People's Liberation Army 2023;48(11):1267-1275
Dexmedetomidine is a highly selective α2 adrenergic receptor agonist,exerting anti-sympathetic,sedative,analgesic and anti-anxiety effects,with minimal impact on respiration.In recent years,dexmedetomidine has been widely used in clinical anesthesia,perioperative treatment,and intensive care.Organ-protection is an important focus of anesthesia and perioperative medicine,with clinical significance in reducing complications and improving short-and long-term outcomes.Increasing clinical evidence and basic research have shown that the application of dexmedetomidine could protect the heart,brain,lung,kidney,liver,gastrointestinal tract and other important organs.The mechanism may be related to dexmedetomidine's effects of anti-inflammation,anti-oxidation,anti-apoptosis,and autophagy regulation.From our perspectives,clinical use should follow the principle of individualization,and the dose should be adjusted in time according to patients'responses,so as to avoid adverse reactions such as hypotension and bradycardia while protecting the organs.Moreover,more strictly designed clinical studies and in-depth mechanistic investigations are needed for the optimal dexmedetomidine therapy and better organ protection during the perioperative course.In order to facilitate better understanding of clinicians,this paper reviews the organ-protective effects and underlying mechanisms of dexmedetomidine.
6.A prospective cohort study on the clinical value of pelvic peritoneal reconstruction in laparoscopic anterior resection for middle and low rectal cancer.
Li Qiang JI ; Zheng LOU ; Hai Feng GONG ; Jin Ke SUI ; Fu Ao CAO ; Guan Yu YU ; Xiao Ming ZHU ; Nan Xin ZHENG ; Rong Gui MENG ; Wei ZHANG
Chinese Journal of Gastrointestinal Surgery 2022;25(4):336-341
Objective: To investigate the safety and efficacy of pelvic peritoneal reconstruction and its effect on anal function in laparoscopy-assisted anterior resection of low and middle rectal cancer. Methods: A prospective cohort study was conducted. Consecutive patients with low and middle rectal cancer who underwent laparoscopy-assisted transabdominal anterior resection at Naval Military Medical University Changhai Hospital from February 2020 to February 2021 were enrolled. Inclusion criteria: (1) the distance from tumor to the anal verge ≤10 cm; (2) laparoscopy-assisted transabdominal anterior resection of rectal cancer; (3) complete clinical data; (4) rectal adenocarcinoma diagnosed by postoperative pathology. Exclusion criteria: (1) emergency surgery; (2) patients with a history of anal dysfunction or anal surgery; (3) preoperative diagnosis of distant (liver, lung) metastasis; (4) intestinal obstruction; (5) conversion to open surgery for various reasons. The pelvic floor was reconstructed using SXMD1B405 (Stratafix helical PGA-PCL, Ethicon). The first needle was sutured from the left anterior wall of the neorectum to the right. Insertion of the needle was continued to suture the root of the sigmoid mesentery while the Hemo-lok was used to fix the suture. The second needle was started from the beginning of the first needle, after 3-4 needles, a drainage tube was inserted through the left lower abdominal trocar to the presacral space. Then, the left peritoneal incision of the descending colon was sutured, after which Hemo-lok fixation was performed. The operative time, perioperative complications, postoperative Wexner anal function score and low anterior resection syndrome (LARS) score were compared between the study group and the control group. Three to six months after the operation, pelvic MRI was performed to observe and compare the pelvic floor anatomical structure of the two groups. Results: A total of 230 patients were enrolled, including 58 who underwent pelvic floor peritoneum reconstruction as the study group and 172 who did not undergo pelvic floor peritoneum reconstruction as the control group. There were no significant differences in general data between the two groups (all P>0.05). The operation time of the study group was longer than that of control group [(177.5±33.0) minutes vs. (148.7±45.5) minutes, P<0.001]. There was no significant difference in the incidence of perioperative complications (including anastomotic leakage, anastomotic bleeding, postoperative pneumonia, urinary tract infection, deep vein thrombosis, and intestinal obstruction) between the two groups (all P>0.05). Eight cases had anastomotic leakage, of whom 2 cases (3.4%) in the study group were discharged after conservative treatment, 5 cases (2.9%) of other 6 cases (3.5%) in the control group were discharged after the secondary surgical treatment. The Wexner score and LARS score were 3.1±2.8 and 23.0 (16.0-28.0) in the study group, which were lower than those in the control group [4.7±3.4 and 27.0 (18.0-32.0)], and the differences were statistically significant (t=-3.018, P=0.003 and Z=-2.257, P=0.024). Severe LARS was 16.5% (7/45) in study group and 35.5% (50/141) in control group, and the difference was no significant differences (Z=4.373, P=0.373). Pelvic MRI examination 3 to 6 months after surgery showed that the incidence of intestinal accumulation in the pelvic floor was 9.1% (3/33) in study group and 46.4% (64/138) in control group (χ(2)=15.537, P<0.001). Conclusion: Pelvic peritoneal reconstruction using stratafix in laparoscopic anterior resection of middle and low rectal cancer is safe and feasible, which may reduce the probability of the secondary operation in patients with anastomotic leakage and significantly improve postoperative anal function.
Anastomotic Leak/surgery*
;
Humans
;
Intestinal Obstruction/surgery*
;
Laparoscopy
;
Postoperative Complications/surgery*
;
Prospective Studies
;
Rectal Diseases/surgery*
;
Rectal Neoplasms/surgery*
;
Retrospective Studies
;
Syndrome
;
Treatment Outcome
7.Preclinical study of T cell receptor specifically reactive with KRAS G12V mutation in the treatment of malignant tumors.
Xiao Jing CHENG ; Dong JIANG ; Lian Hai ZHANG ; Jiang Hua WANG ; Ya Zhen LI ; Jia Hui ZHAI ; Bao Qi YAN ; Lu Lu ZHANG ; Xing Wang XIE ; Zi Yu LI ; Jia Fu JI
Journal of Peking University(Health Sciences) 2022;54(5):884-895
OBJECTIVE:
KRAS gene is one of the most common mutations of proto-oncogenes in human tumors, G12V is one of the most common mutation types for KRAS. It's challenging to chemically acquire the targeted drug for this mutation. Recent studies reported that this mutation peptides can form a neoepitope for T cell recognition. Our study aims to clone the T cell receptor (TCR) which specifically recognizes the neoepitope for KRAS G12V mutation and constructs TCR engineered T cells (TCR-T), and to investigate if TCR-Ts have strong antitumor response ability.
METHODS:
In this study, tumor infiltrating lymphocytes were obtained from one colorectal cancer patient carrying KRAS G12V mutation. Tumor-reactive TCR was obtained by single-cell RT-5' rapid-amplification of cDNA ends PCR analysis and introduced into peripheral blood lymphocytes to generate TCR-Ts.
RESULTS:
We obtained a high-affinity TCR sequence that specifically recognized the HLA-A*11:01-restricted KRAS G12V8-16 epitope: KVA11-01. KVA11-01 TCR-T could significantly kill various tumor cells such as PANC-1, SW480 and HeLa (overexpressing HLA-A*11:01 and KRAS G12V), and secreting high levels of interferon-γ (IFN-γ). Non-specific killing experiments suggested KVA11-01 specifically recognized tumor cells expressing both mutant KRAS G12V and HLA-A*11:01. In vivo assay, tumor inhibition experiments demonstrated that infusion of approximately 1E7 KVA11-01 TCR-T could significantly inhibit the growth of subcuta-neously transplanted tumors of PANC-1 and HeLa (overexpressing HLA-A*11:01 and KRAS G12V) cells in nude mice. No destruction of the morphologies of the liver, spleen and brain were observed. We also found that KVA11-01 TCR-T could significantly infiltrate into tumor tissue and had a better homing ability.
CONCLUSION
KVA11-01 TCR-T cells can effectively target a variety of malignant tumor cells carrying KRAS G12V mutation through in vitro and in vivo assay. KVA11-01 TCR-T cells have excellent biological activity, high specificity of target antigen and homing ability into solid tumor tissue. KVA11-01 TCR-T is expected to be an effective treatment for patients with KRAS G12V mutant solid malignancies.
Animals
;
DNA, Complementary
;
Epitopes
;
HLA-A Antigens
;
Humans
;
Interferon-gamma
;
Mice
;
Mice, Nude
;
Mutation
;
Neoplasms
;
Proto-Oncogene Proteins p21(ras)/genetics*
;
Receptors, Antigen, T-Cell/genetics*
8.Peripheral zone PSA density: a predominant variable to improve prostate cancer detection efficiency in men with PSA higher than 4 ng ml
Cheng WANG ; Yue-Yang WANG ; Shi-Yuan WANG ; Ji-Xiang DING ; Mao DING ; Yuan RUAN ; Xiao-Hai WANG ; Yi-Feng JING ; Bang-Min HAN ; Shu-Jie XIA ; Chen-Yi JIANG ; Fu-Jun ZHAO
Asian Journal of Andrology 2021;23(4):415-420
To improve the diagnostic efficiency of prostate cancer (PCa) and reduce unnecessary biopsies, we defined and analyzed the diagnostic efficiency of peripheral zone prostate-specific antigen (PSA) density (PZ-PSAD). Patients who underwent systematic 12-core prostate biopsies in Shanghai General Hospital (Shanghai, China) between January 2012 and January 2018 were retrospectively identified (n = 529). Another group of patients with benign prostatic hyperplasia (n = 100) were randomly preselected to obtain the PSA density of the non-PCa cohort (N-PSAD). Prostate volumes and transition zone volumes were measured using multiparameter magnetic resonance imaging (mpMRI) and were combined with PSA and N-PSAD to obtain the PZ-PSAD from a specific algorithm. Receiver operating characteristic (ROC) curve analysis was used to assess the PCa detection efficiency in patients stratified by PSA level, and the area under the ROC curve (AUC) of PZ-PSAD was higher than that of PSA, PSA density (PSAD), and transition zone PSA density (TZ-PSAD). PZ-PSAD could amend the diagnosis for more than half of the patients with inaccurate transrectal ultrasonography (TRUS) and mpMRI results. When TRUS and mpMRI findings were ambiguous to predict PCa (PIRADS score ≤3), PZ-PSAD could increase the positive rate of biopsy from 21.7% to 54.7%, and help 63.8% (150/235) of patients avoid unnecessary prostate biopsy. In patients whose PSA was 4.0-10.0 ng ml
9.Expression and clinicopathological significance of Bcl - 2 and Bax genes in colorectal cancer patients complicated with schistosomiasis
Xing-Guang YANG ; Ji-Wu YANG ; Peng-Ju ZHAO ; Wei CHENG ; Hai-Bin SHI ; Bin ZHANG ; Qi-Chun FU ; Yi LI
Chinese Journal of Schistosomiasis Control 2021;33(2):148-153
Objective To investigate the expression and clinicopathological significance of Bcl-2 and Bax genes in colorectal cancer (CRC) patients complicated with schistosomiasis. Methods The CRC patients receiving surgical treatment in the First Affiliated Hospital of Dali University from June 2016 to June 2020 were recruited as the study subjects, and 30 subjects were randomly sampled from the CRC patients complicated with schistosomiasis (CRC-S group) and 30 subjects were randomly sampled from the CRC patients without schistosomiasis (CRC group) using a random number table method. The cancer specimens were sampled from subjects in the CRC-S and CRC groups, and the peri-cancer specimens were sampled from subjects in the CRC group. The Bcl-2 and Bax expression was quantified in cancer and peri-cancer specimens using a real-time fluorescent quantitative PCR (qPCR) assay and immunohistochemistry at transcriptional and translational levels, and the cell apoptosis was detected in cancer specimens using HE staining. Results A total of 60 subjects were enrolled, including 30 cases in the CRC group and 30 cases in the CRC-S group. There were no significant differences between the two groups in terms of gender distribution (χ2 = 0.271, P > 0.05), mean age (t = -0.596, P > 0.05), tumor growth pattern (χ2 = 0.275, P > 0.05), tumor location (χ2 = 4.008, P > 0.05), tumor invasion depth (χ2 = 0.608, P > 0.05), degree of tumor differentiation (χ2 = 0.364, P > 0.05), or presence of vascular metastasis (χ2 = 1.111, P > 0.05), while significant differences were seen between the two groups in terms of histological type, presence of lymph node metastasis and TMN staging (χ2 = 5.963, 8.297 and 5.711, all P values < 0.05). qPCR assay and immunohistochemistry quantified significantly higher Bcl-2 and Bax expression in cancer specimens from the CRC and CRC-S groups than in the peri-cancer specimens from the CRC group at both translational and transcriptional levels (all P values < 0.05), and higher Bcl-2 and lower Bax expression were seen in the cancer specimens from the CSC-S group than that from the CRC group (all P values < 0.05). In addition, the cell apoptotic rate was significantly greater in the cancer specimens in the CRC group than in the CRC-S group (42.00% vs. 23.35%; χ2 = 41.500, P = 0.000). Conclusion Schistosomiasis may be involved in the development and progression of CRC through affecting Bcl-2 and Bax gene expression in the apoptosis signaling pathway.
10.Epidemiological investigation of allergic rhinitis in central cities and countrysides of Inner Mongolia region.
Zhuo Yi DENG ; Xiao Jia LIU ; Ri Na SA ; Hai Xia XU ; Qiang FU ; Dong Yue XU ; Xiao Bo CUI ; Ji LIU ; Bo Long SONG ; Ming ZHENG ; Yu Hui OUYANG ; Xiang Dong WANG ; Xiao Ling LIU
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2021;56(6):635-642
Objective: To investigate the prevalence of allergic rhinitis (AR) in 3 central cities (Chifeng, Hohhot, Ordos) and the surrounding rural areas of Inner Mongolia region, and to look for possible risk factors related to the disease. Methods: From March to October of 2019, a multi-stage stratified random sampling epidemiological survey was conducted in Chifeng, Hohhot, Ordos and rural areas. The AR-related factors of the population were obtained in the form of face-to-face questionnaire survey, and the skin prick test (SPT) was taken for the participants. AR disease was diagnosed according to the "Guidelines for the Diagnosis and Treatment of Allergic Rhinitis (2015, Tianjin)". The daily airborne pollen situation in the three regions was monitored during the same period. SPSS 23.0 was used to analyze all survey results. Results: A total of 6 818 questionnaires were recovered, with 6 393 valid questionnaires. The self-reported prevalence of AR was 27.72% (1 772/6 393) and the confirmed prevalence of AR was 17.10% (1 093/6 393). The prevalence of perennial AR was 1.83% (117/6 393) while the prevalence of seasonal AR was 15.27% (976/6 393). The prevalence of AR diagnosed in females was higher than that in males (19.19% vs 15.34%, χ²=16.594, P<0.001) and the prevalence of females in the two age groups of 36-45 years and 46-55 years was significantly higher than that of males (18.17% vs 9.73%, 14.13% vs 7.25%, χ2 value was 23.848, 18.772, respectively, all P<0.001). The prevalence of confirmed diagnoses in ethnic minorities was higher than that of Han nationality, and the prevalence of confirmed diagnoses in urban areas was higher than that in rural areas (23.13% vs 16.20%, 27.27% vs 9.71%, χ2 value was 24.516, 336.024, respectively, all P<0.001). The main nasal symptoms of AR patients were sneezing (91.31%), nasal congestion (85.91%) and nasal itching (85.00%). The most common concomitant disease of AR was allergic conjunctivitis (73.99%). Asthma (OR=6.629), food allergy (OR=3.236), drug allergy (OR=1.786), application of antibiotics (OR=1.553), recent home decoration (OR=2.307), and smoking (OR=1.322) were the AR related risk factors. The highest proportion of SPT positive reactions was Artemisia annua (80.15%). The peak period of clinical symptoms of AR patients in Inner Mongolia region was July to September, which was consistent with the second peak period of airborne pollen monitoring. Conclusions: The prevalence of AR in central cities and the surrounding rural areas of Inner Mongolia region is 17.10%, and Artemisia species is the most important pollen allergen in this area. History of asthma, food allergy, drug allergy, antibiotic use, home decoration and smoking history are the related risk factors for AR.
Adult
;
Allergens
;
China/epidemiology*
;
Female
;
Humans
;
Male
;
Middle Aged
;
Pollen
;
Prevalence
;
Rhinitis, Allergic/epidemiology*
;
Rhinitis, Allergic, Seasonal
;
Urbanization

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