1.Retrospective analysis of a tuberculosis outbreak among junior high school students in Chongqing
LI Jianqiong, ZHANG Ting, CHEN Aihua, WANG Qingya, ZHANG Ya, CHEN Jian, TANG Jie, LI Liang
Chinese Journal of School Health 2026;47(5):741-746
Objective:
To analyze changes in tuberculosis infection among junior high school students before and after tuberculosis exposure, so as to provide a reference for improving school tuberculosis prevention and control measures and policy formulation.
Methods:
Retrospectively collect data on a tuberculosis outbreak that occurred in a grade of a junior high school in Chongqing in 2025, including tuberculosis screening records of students in this grade upon their enrollment in 2022 (1 156 students) and after two tuberculosis outbreaks in 2023 (206 students) and 2025 (171 students). The Wilcoxon signed rank test for paired design was used to compare the induration diameters of the subjects, and the Chi square test was adopted to analyze the rate of tuberculosis infection among students.
Results:
In the tuberculosis outbreak in 2023, the rate of tuberculosis infection among close contacts ( 11.84 %) and the rate of tuberculosis infection among freshrman at school enrollment (12.89%) showed no statistically significant difference ( χ 2=0.25, P >0.05). The rate of tuberculosis infection of close contacts in the 2025 tuberculosis outbreak (55.56%) was higher than that in the 2023 outbreak (11.84%) ( χ 2=30.42, P <0.01). Among the 106 students included in the cohort analysis, the median induration diameter was 3.50 (1.50, 7.50) mm in 2023 and 8.75 (4.25, 11.50) mm in 2025, with a statistically significant difference ( Z=-5.76, P <0.01). There was no statistically significant difference between the infection rate in 2022 (16.98%) and that in 2023 (10.38%) ( χ 2=1.96, P =0.16). The infection rate in 2025 (43.40%) was higher than those in 2022 and 2023 ( χ 2=17.55, 29.39, both P <0.017). The seroconversion rate of students in the same class in 2025 ( 58.00 %) was higher than that of students in different classes (16.07%), with a statistically significant difference ( χ 2=20.19, P <0.01). All 72 individuals with latent tuberculosis infections identified during the pandemic in 2023 and 2025 refused to undergo prophylactic treatment.
Conclusions
The lack of preventive treatment may be the underlying cause of the successive outbreaks during the epidemic. Early detection of infection sources and standardized outbreak management are crucial to controlling the spread of the epidemic.
2.Pollution levels and health risk assessment of nitrosamines in pipeline direct drinking water from primary and secondary schools in Shanghai
Ting WANG ; Chaoye SHEN ; Zhe CHEN ; Jian CHEN ; Yi SU
Journal of Environmental and Occupational Medicine 2026;43(5):637-642
Background Nitrosamines (NAms), emerging as disinfection by-products in drinking water, are highly carcinogenic. Given the significant NAms contamination reported in various regions of China, evaluating the contamination levels and health risks of NAms in terminal direct drinking water is of great urgency. Objective To investigate the concentration levels of NAms in piped direct drinking water at primary and secondary schools in Shanghai, and to assess the potential health risks posed to different age groups through this exposure pathway. Methods A total of 198 water samples were collected from 66 primary and secondary schools across five districts in Shanghai from May to June 2023. The mass concentrations of eight major NAms were quantified using solid-phase extraction coupled with gas chromatography-mass spectrometry (GC-MS). A carcinogenic health risk model was employed to evaluate the lifetime cancer risks associated with NAms exposure via direct drinking water for various age groups. Results Among the 198 samples, NAms were detected in 196 samples, with concentrationsranging from below the limit of detection (LOD) to 106.06 ng·L−1. The average concentration of total NAms was 21.30 ng·L−1, with N-nitrosodimethylamine (NDMA) exhibiting the highest detection rate at 98.5%. Significant differences in NAms concentrations were observed among water treatment systems utilizing ultrafiltration (UF), nanofiltration (NF), and reverse osmosis (RO) as core processes (P<0.05). The lifetime cancer risks for different age groups ranged from 1.38×10−6 to 1.11×10−5, with NDMA contributing the most to the overall risk (82.1%). The carcinogenic risk for adults (1.08×10−5) was higher than that for children and adolescents (1.38×10−6 to 2.61×10−6). Among children and adolescents under 18 years of age, the risk decreased as age increased. Conclusion Trace levels of NAms, primarily NDMA, are detected in the piped direct drinking water at primary and secondary schools in Shanghai, with concentrations vary significantly depending on the water treatment process. The carcinogenic risks of NAms exposure via direct drinking water for all age groups are below the acceptable level (1×10−4) recommended by the U.S. Environmental Protection Agency (EPA).
3.Pollution levels and health risk assessment of nitrosamines in pipeline direct drinking water from primary and secondary schools in Shanghai
Ting WANG ; Chaoye SHEN ; Zhe CHEN ; Jian CHEN ; Yi SU
Journal of Environmental and Occupational Medicine 2026;43(5):637-642
Background Nitrosamines (NAms), emerging as disinfection by-products in drinking water, are highly carcinogenic. Given the significant NAms contamination reported in various regions of China, evaluating the contamination levels and health risks of NAms in terminal direct drinking water is of great urgency. Objective To investigate the concentration levels of NAms in piped direct drinking water at primary and secondary schools in Shanghai, and to assess the potential health risks posed to different age groups through this exposure pathway. Methods A total of 198 water samples were collected from 66 primary and secondary schools across five districts in Shanghai from May to June 2023. The mass concentrations of eight major NAms were quantified using solid-phase extraction coupled with gas chromatography-mass spectrometry (GC-MS). A carcinogenic health risk model was employed to evaluate the lifetime cancer risks associated with NAms exposure via direct drinking water for various age groups. Results Among the 198 samples, NAms were detected in 196 samples, with concentrationsranging from below the limit of detection (LOD) to 106.06 ng·L−1. The average concentration of total NAms was 21.30 ng·L−1, with N-nitrosodimethylamine (NDMA) exhibiting the highest detection rate at 98.5%. Significant differences in NAms concentrations were observed among water treatment systems utilizing ultrafiltration (UF), nanofiltration (NF), and reverse osmosis (RO) as core processes (P<0.05). The lifetime cancer risks for different age groups ranged from 1.38×10−6 to 1.11×10−5, with NDMA contributing the most to the overall risk (82.1%). The carcinogenic risk for adults (1.08×10−5) was higher than that for children and adolescents (1.38×10−6 to 2.61×10−6). Among children and adolescents under 18 years of age, the risk decreased as age increased. Conclusion Trace levels of NAms, primarily NDMA, are detected in the piped direct drinking water at primary and secondary schools in Shanghai, with concentrations vary significantly depending on the water treatment process. The carcinogenic risks of NAms exposure via direct drinking water for all age groups are below the acceptable level (1×10−4) recommended by the U.S. Environmental Protection Agency (EPA).
4.Exploring schizophrenia pathogenesis and treatment from the perspective of spirit,soul,and inferior spirit
Yuling WANG ; Xiaonan XU ; Ting FANG ; Han XU ; Shuran ZHOU ; Xiangning CUI ; Jian WANG
Journal of Beijing University of Traditional Chinese Medicine 2025;48(10):1352-1357
Schizophrenia is a prevalent mental-behavioral disorder characterized by perceptual disturbances,affective dysregulation,and behavioral abnormalities.In traditional Chinese medicine,it is classified under"manic depressive psychosis"according to its symptomatology.The concepts of"spirit,soul,and inferior spirit"originate from Lingshu·Benshen.Drawing on the concept of"spirit governs the soul and inferior spirit"from Lei Jing,this study explored schizophrenia pathogenesis and treatment from the perspective of the three-level regulation of spirit,soul,and inferior spirit.The core pathogenesis involves failure of spirit to govern as the root cause,disruption of soul homing as the pathodynamic process,and the loss of inferior spirit's somatic functional expression as the manifestation.The pathological locations are the heart,liver,and lungs.Therapeutic strategies are developed according to the pathological transmission pattern"spirit derangement,soul floating,inferior spirit dissipation,"forming a treatment system that emphasizes"calming the heart and tranquillization,restoring its control to solidify the root;suppressing the liver soul and regulating the central mechanism to pacify excess to stop mania;purifying the lungs and calming the inferior spirit to restore its clarity and regulate sensory perception and restore cognition."The treatment emphasizes the synergistic use of"calming the spirit,stabilizing the soul,and soothing the inferior spirit,"and combines acupuncture and repetitive transcranial magnetic stimulation and other treatments to treat both the manifestation and root cause of schizophrenia.Exploring the syndrome differentiation and treatment of schizophrenia from the perspective of spirit,soul,and inferior spirit,aiming to provide a theoretical basis for the treatment of schizophrenia with traditional Chinese medicine.
5.The impact of early enteral nutrition on intestinal function in patients with complicated intra-abdominal infection
Shuang-Shuang QIU ; Yan-Hua WANG ; Qiao-Hong HONG ; Cui-Ping ZENG ; Jian-Ting CHEN ; Jian-She SHI
Parenteral & Enteral Nutrition 2025;32(2):95-100
Objective:To investigate the effect of early enteral nutrition on intestinal function in patients with complicated intra-abdominal infection.Methods:In this study,a prospective single-center randomized controlled trial was used to select 88 patients with severe abdominal infections in the surgical intensive care ward from January 2021 to December 2023.Among them,65 patients were eligible and were randomly divided into 33cases in the intervention group(who received early enteral nutrition),and 32cases in the control group(who did not receive early enteral nutrition).The clinical baseline characteristics of the two groups,conditions such as abdominal distension and diarrhea during enteral nutrition,intra-abdominal pressure,the time to reach the standard of complete enteral nutrition,and the indexes of pre-albumin,CRP,and leukocyte count on the third and the seventh day postoperative day were observed.The t-test was used to compare between groups for normally distributed measures.The Mann-Whitney U test was used to compare between groups for skewed measures.The χ2 test or continuity-corrected χ2 test was used to compare the count data between groups.Repeated measures data were analyzed by repeated measures ANOVA.Results:The clinical baseline characteristics of the two groups were completely matched;There were significant differences in the changes of intra-abdominal pressure over time between the two groups(Fgroup=9.665,P=0.004),There were significant differences in the changes of intra-abdominal pressure over time between the two intervention group(Ftime=64.124,P<0.001)and the control group.and the trend of intra-abdominal pressure reduction in the intervention group was more significant than that in the control group(Finteractive=3.938,P=0.023);The time required for the recovery of bowel sounds was significantly shorter in the experimental group than in the control group[(19.5±3.5)h vs(35.3±4.5)h,P<0.001,t=15.829];there was no significant difference in the frequency of abdominal distention,vomiting and aspiration between the two groups(P>0.05),and the difference in the frequency of diarrhea was statistically significant(P=0.003);The time to reach the standard of enteral nutrition in the intervention group was shorter than that in the control group[(6.3±1.2)d vs(7.4±1.5)d,P=0.002];The total hospital stay of the intervention group was significantly shorter than that of the control group[(11±3.2)d vs(14±4.1)d,P=0.007].The prealbumin(0.21±0.2,0.28±0.2)g/L,CRP(175.5±23.6,45.4±14.5)mg/L,and white blood cell count(11.7±2.9,9.1±3.5)109/L of the intervention group on the 3rd and 7th days after surgery were significantly improved compared with those of the control group(P<0.05).Conclusion:Early enteral nutrition can effectively promote the recovery of intestinal function in patients with complicated intra-abdominal infection.
6.Compound Xishu Granules Inhibit Proliferation of Hepatocellular Carcinoma Cells by Regulating Ferroptosis
Yuan TIAN ; Yuxi WANG ; Zhen LIU ; Yuncheng MA ; Hongyu ZHU ; Xiaozhu WANG ; Qian LI ; Jian GAO ; Weiling WANG ; Wenhui XU ; Ting WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):37-45
ObjectiveTo study the mechanism of compound Xishu granules (CXG) in inhibiting the proliferation of hepatocellular carcinoma cells by regulating ferroptosis. MethodsThe transplanted tumor model of human Huh7 was established with nude mice and the successfully modeled mice were randomized into model, Fufang Banmao (0.21 g·kg-1), low-dose (1.87 g·kg-1) CXG, medium-dose (3.74 g·kg-1) CXG, and high-dose (7.49 g·kg-1) CXG groups. Mice were administrated with drinking water or CXG for 28 days, and the body weight and tumor volume were measured every 4 days. Hematoxylin-eosin staining was employed to observe the histopathological changes of tumors. The cell-counting kit-8 (CCK-8) was used to examine the survival rate of Huh7 cells treated with different concentrations (0, 31.25, 62.5, 125, 250, 500, 1 000 mg·L-1) of CXG for 24 h and 48 h. CA-AM, DCFH-DA, and C11-BODIPY581/591 fluorescent probes were used to determine the intracellular levels of ferrous ion (Fe2+), reactive oxygen species (ROS), and lipid peroxide (LPO), respectively. The colorimetric method was employed to measure the levels of glutathione (GSH) and superoxide dismutase (SOD). Western blot was employed to determine the protein levels of glutathione peroxidase 4 (GPX4), transferrin receptor 1 (TFR1), and ferritin heavy chain 1 (FTH1), respectively. ResultsIn the animal experiment, compared with the model group, the drug treatment groups showed reductions in the tumor volume from day 12 (P<0.01). After treatment, the Fufang Banmao and low-, medium-, and high-dose CXG groups had lower tumor volume, relative tumor volume, and tumor weight than the model group (P<0.05), with tumor inhibition rates of 48.99%, 79.93%, 91.38%, and 97.36%, respectively. Moreover, the CXG groups had lower tumor volume and relative tumor volume (P<0.05 in all the three dose groups) and lower tumor weight (P<0.05 in medium-dose and high-dose groups) than the Fufang Banmao group. Compared with the model group, the drug treatment groups showed reduced number of tumor cells, necrotic foci with karyopyknosis, nuclear fragmentation, and nucleolysis, and the high-dose CXG group showed an increase in the proportion of interstitial fibroblasts. In the cell experiment, compared with the blank group, CXG reduced the survival rate of Huh7 cells in a dose-dependent manner after incubation for 24 h and 48 h (P<0.05). Compared with the blank group, the RSL3 group and the low-, medium-, and high-dose CXG groups showed a decrease in the relative fluorescence intensity of CA-AM and increases in the fluorescence intensity of DCFH-DA and fluorescence ratio of C11-BODIPY581/591, which indicated elevations in the levels of Fe2+ (P<0.01), ROS (P<0.05), and LPO (P<0.01), respectively. Compared with the blank group, the RSL3 and low-, medium-, and high-dose CXG groups showed lowered levels of GSH and SOD (P<0.05). In addition, the RSL3 group and the medium- and high-dose CXG groups showed down-regulated expression of GPX4 and FTH1 (P<0.05), and the low- and high-dose CXG groups presented up-regulated expression of TFR1 (P<0.05). ConclusionCXG suppresses the proliferation of hepatocellular carcinoma cells by inducing ferroptosis via downregulating the GSH-GPX4 signaling axis and increasing intracellular Fe2+and LPO levels.
7.Effects of Jiedu Yizhi Formula on neuroinflammation in a mouse model of Alzheimer's disease via PI3K/Akt/mTOR signaling pathway
Jie WANG ; Jian LIU ; Xiao-ting ZHU ; Yun-qiang LI ; Xin-yue ZHANG ; Fan LI ; Jia-li WU ; Wei LI ; Ming-quan LI
Chinese Traditional Patent Medicine 2025;47(6):1843-1852
AIM To investigate the mechanism of Jiedu Yizhi Formula on cognitive function and neuroinflammation in a mouse model of Alzheimer's disease(AD).METHODS 50 APP/PS1 double transgenic mice were randomly divided into the model group,the donepezil group,and the low-dose,moderate-dose,and high-dose Jiedu Yizhi Formula group(1.78,3.56 and 7.12 g/kg),with 10 mice in each group,in contrast to the 10 WT mice of the blank group.Following anesthesia administration and 8-week oral gavage regimen with respective drugs,all mice underwent final tissue sample collection.The mice had their learning and memory ability assessed by Morris water maze and nesting behavior scores;their pathology of brain tissue and Aβ expression observed using HE,Nissl and IHC staining;their polarization of microglia and the expression of inflammatory factors in hippocampal tissue detected by IF and ELISA;their hippocampal expression of PI3K/Akt/mTOR signaling pathway detected by RT-qPCR and Western blot.RESULTS Compared with the blank group,the model group had lower scores in total swimming distance,frequency in crossing the platform,residence time in the target quadrant,and nesting behavior scores(P<0.05,P<0.01);prolonged evasion latency(P<0.01);more disorganized arrangement of pyramidal cells,solidification and deep staining,unclear demarcation,irregular cell shapes,reduction of Nyctinidia,and increased Aβ deposition in the brain tissue(P<0.01);elevated expression of hippocampal microglia M1-type markers CD16/32 and lba-1(P<0.01);decreased levels of M2-type marker CD206(P<0.05);elevated levels of TNF-α and IL-1β(P<0.01);decreased expressions of IL-13 and IL-4(P<0.01);and decreased levels of PI3K,Akt and mTOR mRNA,and reduced p-PI3K,p-Akt and p-mTOR protein expressions(P<0.01).Compared to the model group,the donepezil group and the Jiedu Yizhi Formula groups showed statistically significant improvements in the aforementioned indexes(P<0.05,P<0.01),with the magnitude of improvement being higher in the high-dose Jiedu Yizhi Formula group.CONCLUSION Jiedu Yizhi Formula suppresses microglia Ml-type polarization while enhancing M2-type polarization via activation the PI3K/Akt/mTOR signaling pathway,which subsequently reduces inflammatory cytokine secretion.This mechanism attenuates Aβ deposition in brain tissues and ameliorates cognitive dysfunction in AD mouse models.
8.Study on the occlusal stability after three years of full-mouth occlusal reconstruction in maximum intercuspal position
Yuxuan WANG ; Tongkai XU ; Jian LI ; Ting JIANG
Chinese Journal of Stomatology 2025;60(2):132-139
Objective:To observe the stability of vertical dimension of occlusion (VDO) and mandibular position in full-mouth occlusal reconstruction subjects by means of digital occlusal analysis.Methods:Six subjects who had completed full-mouth occlusal reconstruction by intraoral functional generated path technique for more than three years in the Department of Prosthodontics, Peking University School and Hospital of Stomatology were enrolled for follow-up observation, all six patients were male, with an age of (53.6±8.4) years. The digital dentition model and occlusal contact at baseline and three years follow-up review after restoration were recorded by intraoral laser scanning, and the changes in occlusal surface morphology, occlusal contact area and mandibular position (mandibular overall deviation and mandibular reference plane average angle deviation) were measured in reverse engineering software. The Wilcoxon signed rank test was used to statistically analyze the changes of horizontal and vertical overbite of anterior teeth and VDO of posterior teeth between baseline and three years follow-up after reconstruction.Results:The prosthesis in the 6 subjects were intact at the time of follow-up, and there was no significant change in occlusal morphology compared with that at the baseline right after restoration delivery, and the occlusal contact in maximum intercuspid position was stable. The overall deviation of the lower jaw was (0.19±0.06) mm, and the angular deviation of the mandibular reference plane was 0.72°±0.38°. The chromatic scale of occlusal contact showed that the occlusal contact in some areas was heavier during the three years post-delivery, and the overbite of anterior teeth and the VDO of posterior teeth showed no statistical difference compared with that in the baseline (all P>0.05). Conclusions:This study suggests that the occlusal contact distribution and jaw position relationship can be maintained after 3 years of full-mouth occlusal reconstruction, and there is no significant change in the anterior overbite and VDO.
9.Effects of Jiedu Yizhi Formula on neuroinflammation in a mouse model of Alzheimer's disease via PI3K/Akt/mTOR signaling pathway
Jie WANG ; Jian LIU ; Xiao-ting ZHU ; Yun-qiang LI ; Xin-yue ZHANG ; Fan LI ; Jia-li WU ; Wei LI ; Ming-quan LI
Chinese Traditional Patent Medicine 2025;47(6):1843-1852
AIM To investigate the mechanism of Jiedu Yizhi Formula on cognitive function and neuroinflammation in a mouse model of Alzheimer's disease(AD).METHODS 50 APP/PS1 double transgenic mice were randomly divided into the model group,the donepezil group,and the low-dose,moderate-dose,and high-dose Jiedu Yizhi Formula group(1.78,3.56 and 7.12 g/kg),with 10 mice in each group,in contrast to the 10 WT mice of the blank group.Following anesthesia administration and 8-week oral gavage regimen with respective drugs,all mice underwent final tissue sample collection.The mice had their learning and memory ability assessed by Morris water maze and nesting behavior scores;their pathology of brain tissue and Aβ expression observed using HE,Nissl and IHC staining;their polarization of microglia and the expression of inflammatory factors in hippocampal tissue detected by IF and ELISA;their hippocampal expression of PI3K/Akt/mTOR signaling pathway detected by RT-qPCR and Western blot.RESULTS Compared with the blank group,the model group had lower scores in total swimming distance,frequency in crossing the platform,residence time in the target quadrant,and nesting behavior scores(P<0.05,P<0.01);prolonged evasion latency(P<0.01);more disorganized arrangement of pyramidal cells,solidification and deep staining,unclear demarcation,irregular cell shapes,reduction of Nyctinidia,and increased Aβ deposition in the brain tissue(P<0.01);elevated expression of hippocampal microglia M1-type markers CD16/32 and lba-1(P<0.01);decreased levels of M2-type marker CD206(P<0.05);elevated levels of TNF-α and IL-1β(P<0.01);decreased expressions of IL-13 and IL-4(P<0.01);and decreased levels of PI3K,Akt and mTOR mRNA,and reduced p-PI3K,p-Akt and p-mTOR protein expressions(P<0.01).Compared to the model group,the donepezil group and the Jiedu Yizhi Formula groups showed statistically significant improvements in the aforementioned indexes(P<0.05,P<0.01),with the magnitude of improvement being higher in the high-dose Jiedu Yizhi Formula group.CONCLUSION Jiedu Yizhi Formula suppresses microglia Ml-type polarization while enhancing M2-type polarization via activation the PI3K/Akt/mTOR signaling pathway,which subsequently reduces inflammatory cytokine secretion.This mechanism attenuates Aβ deposition in brain tissues and ameliorates cognitive dysfunction in AD mouse models.
10.Optimization Study of Rat Models for Sequelae of Pelvic Inflammatory Disease
Zhen LIU ; Wei-ling WANG ; Yun-cheng MA ; Yu-xi WANG ; Yuan TIAN ; Qian LI ; Xiao-zhu WANG ; Xiao-yao LIU ; Mei JIANG ; Wen-hui XU ; Jian GAO ; Ting WANG
Progress in Modern Biomedicine 2025;25(12):1921-1930
Objective:To establish a stable rat model of sequelae of pelvic inflammatory disease(SPID)with clinical characteristics,and to provide a reliable experimental model for the study of the pharmcological effect and mechanism of SPID.Methods:Twenty-four 7-week-old SD rats were divided into sham operation group,model-A(108 cfu/mL mixed bacterial solution,0.2 mL),model-B(109 cfu/mL mixed bacterial solution 0.2 mL),and model-C(108 cfu/mL E.coli 0.2 mL).The weight of the rat's uterine was weighed and the uterine index was calculated.The automatic hematology analyzer was used to detect the blood routine;hematoxylin-eosin staining(HE)and masson staining were used to detect uterine pathlogical changes in rats.Enzyme-linked immunosorbent assay(ELISA)was used to detect interleukin-1β(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in rat uterine tissue homogenates.Western blot was used to detect the expression of proteins related to NF-κB signaling pathway.Results:Compared with the sham operation group,the uterine index of model-A,model-B,and model-C were significantly increased(P<0.05,P<0.01).The levels of WBC and NE in the model-A increased significantly(P<0.01).The level of LY in model-B decreased significantly(P<0.01).The levels of IL-1β,TNF-α in model-A,model-B,and model-C were significantly increased(P<0.01).The levels of IL-6 in model-A and model-B were significantly increased(P<0.05,P<0.01).The collagen volume fraction of model-A and model-B were significantly increased(P<0.01).Mechanism study indicates that the expression levels of p-IKKβ/IKKβ,p-IκBα/IκBα and p-p65/p65 in model-A were significantly increased(P<0.01),and the expression levels of IκBα/β-actin were significantly decreased(P<0.01).The expression level of p-IKKβ/IKKβ in model-B was significantly increased(P<0.01).Conclusions:A stable rat model of SPID that conforms to clinical characteristics can be successfully constructed by combining 0.2 mL of mixed bacterial solution with a concentration of 108 cfu/mL and mechanical injury.This modeling method intervened in the expression of the NF-κB inflammatory signaling pathway.


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