1.Cerebral endothelial 3-mercaptopyruvate sulfurtransferase improves ischemia-induced cognitive impairment via interacting with protein phosphatase 2A.
Li ZHU ; Yi HUANG ; Jing JIN ; Rongjun ZOU ; Rui ZUO ; Yong LUO ; Ziqing SONG ; Linfeng DAI ; Minyi ZHANG ; Qiuhe CHEN ; Yunting WANG ; Wei WANG ; Rongrong HE ; Yang CHEN
Acta Pharmaceutica Sinica B 2025;15(1):314-330
The catalytic activity of 3-mercaptopyruvate (3MP) sulfurtransferase (MPST) converts 3MP to hydrogen sulfide (H2S). However, the regulatory mechanisms governing MPST and its impact on the brain remain largely unexplored. Our study reveals the neuroprotective role of endothelial MPST-generated H2S, regulated by protein phosphatase 2A (PP2A). Bioinformatics analysis and RNA sequencing demonstrated that endothelial PP2A is associated with neurodegenerative disease pathways. Cerebral ischemic mice exhibited significant inactivation of endothelial PP2A, evidenced by the reduction of PP2Acα in the brain endothelium. Mice with endothelium-specific null PP2A (PP2AEC-cKO) exhibited neuronal loss, cognitive dysfunction, and long-term potentiation deficits. Postnatal inactivation of endothelial PP2A also contributes to cognitive dysfunction and neuronal loss. However, regaining endothelial PP2A activity by overexpressing Ppp2ca rescued neuronal dysfunction. Mechanistically, PP2A deficiency is intricately linked to the MPST-H2S signaling pathway. A robust reduction in endothelial MPST-dependent H2S production followed PP2A deficiency. Exogenous H2S treatment and AAV-mediated overexpression of MPST in brain endothelial cells significantly mitigated neuronal dysfunction in PP2AEC-cKO mice. Furthermore, PP2A deficiency promotes an increase in calcium influx and calpain2 phosphorylation, subsequently leading to MPST degradation. The PP2A activator (FTY720) and MPST activator (3MP sodium) both remarkably restored endothelial MPST-dependent H2S production, subsequently rescuing ischemia-induced neurological deficits. In conclusion, our study demonstrates that endothelial PP2A deficiency leads to MPST degradation by activating calpain2, thus damaging neuronal function.
2.Engineering cellular dephosphorylation boosts (+)-borneol production in yeast.
Haiyan ZHANG ; Peng CAI ; Juan GUO ; Jiaoqi GAO ; Linfeng XIE ; Ping SU ; Xiaoxin ZHAI ; Baolong JIN ; Guanghong CUI ; Yongjin J ZHOU ; Luqi HUANG
Acta Pharmaceutica Sinica B 2025;15(2):1171-1182
(+)-Borneol, the main component of "Natural Borneol" in the Chinese Pharmacopoeia, is a high-end spice and precious medicine. Plant extraction cannot meet the increasing demand for (+)-borneol, while microbial biosynthesis offers a sustainable supply route. However, its production was extremely low compared with other monoterpenes, even with extensively optimizing the mevalonate pathway. We found that the key challenge is the complex and unusual dephosphorylation reaction of bornyl diphosphate (BPP), which suffers the side-reaction and the competition from the cellular dephosphorylation process, especially lipid metabolism, thus limiting (+)-borneol synthesis. Here, we systematically optimized the dephosphorylation process by identifying, characterizing phosphatases, and balancing cellular dephosphorylation metabolism. For the first time, we identified two endogenous phosphatases and seven heterologous phosphatases, which significantly increased (+)-borneol production by up to 152%. By engineering BPP dephosphorylation and optimizing the MVA pathway, the production of (+)-borneol was increased by 33.8-fold, which enabled the production of 753 mg/L under fed-batch fermentation in shake flasks, so far the highest reported in the literature. This study showed that rewiring dephosphorylation metabolism was essential for high-level production of (+)-borneol in Saccharomyces cerevisiae, and balancing cellular dephosphorylation is also helpful for efficient biosynthesis of other terpenoids since all whose biosynthesis involves the dephosphorylation procedure.
3.Analysis of individual dose monitoring results of occupational external radiation in radiation workers of non-medical institutions in Shanghai
Tong HUANG ; Hong XIAO ; Xuesong ZHOU ; Minpeng HUANG ; Fajian LUO ; Aijun QIAN ; Linfeng GAO
Journal of Environmental and Occupational Medicine 2025;42(12):1504-1509
Background With the widespread application of ionizing radiation technology in non-medical fields, the number of non-medical radiation workers has steadily increased over the years. Individual dose monitoring serves as a crucial measure to safeguard the occupational health of non-medical radiation workers, as it can accurately identify occupational health risks and optimize radiation protection strategies. Objective To analyze the individual monitoring data of radiation workers from partial non-medical sectors in Shanghai from 2016 to 2023, to obtain the status of occupational radiation exposure and to provide a reference basis for non-medical radiation hygiene supervision and protection management. Methods The study subjects consisted of radiation workers from non-medical institutions in Shanghai who recieved individual dose monitoring at a Class-A radiation health technical service institution between 2016 and 2023. Under the Specifications for individual monitoring of occupational external exposure (GBZ 128-2019), thermoluminescence dosimetry was used for measuring personal dose equivalent, Hp(10), of various occupations encompassing industrial irradiation, industrial radiography, radioisotope production, accelerator operation, other industrial applications, education, and veterinary medicine. Kruskal-Wallis H test was used for comparison among multiple groups, Bonferroni method was adopted for pairwise comparison, and Mann-Kendall test was conducted for trend analysis to analyze the per-capita annual effective dose and its variation over time across different occupational categories of radiation workers. Results A total of
4.Application of machine learning models in predicting renal function decline following robot-assisted partial nephrectomy
Jing LI ; Linfeng WANG ; Gaojie ZHANG ; Yong HUANG ; Yingying GAO ; Rui SUN ; Yang CAO ; Qiuchen LI ; Hao HE ; Ziling WEI ; Jiayu LIU
Journal of Chongqing Medical University 2025;50(4):457-462
Objective:To compare the efficacy of various machine learning models in predicting renal function decline after robot-assisted partial nephrectomy(RAPN),and to provide evidence for clinical risk stratification.Methods:This study retrospectively in-cluded the clinical data of 733 patients with renal cell carcinoma undergoing RAPN at the Urology Department of The First Affiliated Hospital of Chongqing Medical University from January 2019 to December 2023.Demographic characteristics,laboratory indicators,and perioperative parameters were integrated to construct seven machine learning models.Key predictors were interpreted using Shap-ley additive explanations(SHAP).Model performance was evaluated using the area under the receiver operating characteristic curve(AUC).Results:The random forest model demonstrated the best predictive performance(AUC=0.84).SHAP analysis identified neutrophil-to-lymphocyte ratio,tumor diameter,the international normalized ratio of prothrombin time,white blood cell count,and in-traoperative blood loss as significant factors influencing postoperative renal function decline.Conclusion:This study provides a poten-tial predictive tool for clinical practice,aiding in identifying high-risk patients and optimizing postoperative management strategies.
5.Correlation between body mass index and short-term prognosis in patients with acute myocardial infarction complicating cardiogenic shock
Jing CHEN ; Linfeng XIE ; Yuanzhu LI ; Suxin LUO ; Bi HUANG
Chongqing Medicine 2025;54(2):405-412
Objective To assess the correlation between the body mass index(BMI)and short-term prognosis in the patients with acute myocardial infarction complicating cardiogenic shock(AMI-CS).Methods A total of 262 patients with diagnosed AMI-CS hospitalized in this hospital from January 2013 to February 2022 were selected as the study subjects,and a total of 255 patients with AMI-CS were included after excluding the patients with incomplete clinical data,no coronary angiography,loss to follow-up and low BMI(<18.5 kg/m2).Among them,those with BMI of 18.5-<24.0 kg/m2 were included in the normal BMI group(n=150),and those with BMI of≥24.0 kg/m2 were included in the overweight or obese group(n=105).The baseline data,auxiliary examinations and treatment measures of the patients were collected,and the patients who did not die at the time of discharge were followed up by telephone on 30 d after AMI onset,and the survival status of the patients,whether having major adverse cardiovascular events(MACE)occurrence and the occurrence time were obtained.The correlation between BMI and endpoint events was assessed by the COX regression model.Results The proportion of complicating atrial fibrillation,BNP and urea levels in the overweight or obesity group were lower than those in the normal BMI group,the BMI and Hb levels were higher than those in the normal BMI group,and the differences were statistically significant(P<0.05).There was no statistically significant difference in the results of cardiovascular examination between the two groups(P>0.05).The use rate of β-receptor blockers in the overweight or obese group was higher than that in the normal BMI group,and the difference was statistically significant(P<0.05).On 30 d of follow-up,the all-cause mortality rate in the overweight or obese group was 39.0%,which was lower than 44.0%in the normal BMI group,but the difference was not statistically significant(P=0.430);there was no statistically signifi-cant difference in the incidence rate of each MACE event and the total incidence rate of MACE between the two groups(P>0.05).The BMI normal group served as the control,the risk of death and the occurrence risk of MACE events in the overweight or obese group had no significant increase(P>0.05).The short-term prognosis had no significant interaction between BMI and the patients in different subgroups(P>0.05).Con-clusion The short-term prognosis has no significant difference between the overweight/obese AMI-CS pa-tients and normal BMI AMI-Cs patients.
6.Mutual facilitation of Alzheimer disease and sarcopenia:roles of myokines,amyloid proteins,and other factors
Linfeng CHEN ; Mengxia GUO ; Zhong LI ; Xiaoyun HUANG
Chinese Journal of Pathophysiology 2024;40(1):172-179
Increasing age is the most important factor for cognitive impairment.Alzheimer disease(AD)and sarcopenia are significant causes of frailty and disability in older adults.It is important to have an in-depth understanding of the relationship between sarcopenia and AD.Studies have reported that sarcopenia often disturbs the secretion of muscle factors,which may increase the risk of developing dementia.In turn,the pathological feature of dementia,such as the de-position of amyloid β-protein(Aβ),amyloid precursor protein(APP)and tau protein in peripheral neurons,may be related to a decline in muscle function.In particular,the deposition of Aβ and APP may eventually lead to movement disorders and disability.Therefore,we hypothesize that AD and sarcopenia may mutually promote each other's pathological develop-ment.This results in exacerbation of clinical and pathological damage,in which myokine and amyloid proteins play impor-tant roles.However,the interrelationship based on amyloid protein and myokine production has not been discussed in de-tail in other reviews.In this paper,we reference and discuss the studies on this topic,and review the common risk factors for sarcopenia and AD and the potential and mechanisms for mutual improvement.
7.Donor plasma reinfusion flushing of the LRS chamber to prevent CD4+ and CD8+ T lymphopenia
Fanhai LI ; Xiaowen CHEN ; Linfeng ZHOU ; Jieting HUANG ; Xiaofan LI ; Bi ZHONG ; Mei XIAO ; Huaqin LIANG
Chinese Journal of Blood Transfusion 2024;37(9):1058-1062
【Objective】 To explore the effectiveness of using donor plasma reinfusion to flush the leukoreduction system (LRS) chamber during the final reinfusion phase with the Trima Accel automated blood collection system in preventing the reduction of CD4+ and CD8+ T lymphocytes. 【Methods】 A longitudinal and cross-sectional study was designed. CD4+ count<200 cells/μL and CD8+ count<125 cells/μL were considered as the criteria for deficiency. Eighteen first-time platelet donors were followed up. The lymphocyte count was measured at 0, 3-6 and 7-14 times of blood donation in the last 300 days. 170 healthy blood donors who have not donated blood were selected as the control group. According to the cut-off point(October 2021), 88 blood donors who mainly used automatic blood collection system to donate platelet apheresis in the last 365 days(median blood donation times ≥17.5)were divided into three groups(A, B and C)and blood samples were obtained. The time for Groups A, B and C started donating platelet apheresis were as follows: Group A: before October 2019, Group B: from October 2019 to September 2021, Group C: after October 2021. Blood samples were analyzed to obtain blood counts including CD4 + and CD8 + T lymphocytes. Blood samples were analyzed to obtain blood cell counts including CD4+ and CD8+ T lymphocytes. Through a comparative analysis, this study aimed to determine if there are any statistical differences in the detection indices between the follow-up groups with varying frequencies of blood donation, the control group, and groups A, B, and C. This approach was employed to infer the efficacy of donor plasma reinfusion in flushing the leukoreduction system (LRS) chamber for preventing the decline of CD4+ and CD8+ T lymphocytes. 【Results】 Eighteen first-time blood donors who were converted to regular platelet apheresis donors did not show a decrease of CD4 + and CD8 + T lymphocytes in the 5 th and 11 th blood donation (median number of blood donation), and there was no significant difference between the above indexes and those in the 0 th blood donation. Among the previous frequent blood donors, the CD4+ and CD8+ T lymphocyte counts in Group B and Group C are both higher than the standard value, showing no statistical difference from the control group. Among regular blood donors, the CD4+ and CD8+ T lymphocyte counts in groups B and C were higher than the criteria values, and had no statistical difference compared to the control group.The CD4+ T lymphocyte count in Group A was normal, with only one donor in Group A having a CD8+ T lymphocyte count below 125 cells/μL. This donor has donated 281 times of platelet apheresis, and the group he belongs to has started blood donation 2-21 years(median of 5 years) before the adjustment of reinfusion mode. The CD4+ and CD8+ T lymphocyte counts in Group A showed significant differences compared to the control group, with median counts (Group A/Control Group) of 359/521 and 257/372, respectively, P<0.001. In Group A, 0%(0/35) had a CD4+ count below 200 cells/μL, and 2.85%(1/35) of donors had a CD8+ count below 125 cells/μL, which was far lower than the proportion of CD4+ and CD8+ T cell deficiency found in regular apheresis donors by John M. Gansner and Mahboubeh Rahmani. The study showed that the adjustment of the plasma reinfusion mode did not further reduce the T lymphocyte counts in blood donors, but instead further restored the T lymphocyte counts in regular blood donors. This indicated that after the adjustment of plasma reinfusion mode, blood donors might not have lost CD4+ and CD8+ T lymphocytes during blood donation, or only lost a small amount, and can recover even if they donate platelet apheresis frequently. 【Conclusion】 Trima Accel automated blood collection system has a good effect on preventing CD4 + and CD8 + T lymphocytes from being reduced by flushing the LRS chamber with donor plasma.
8.Total α and β radioactivity levels of source water in two areas of Shanghai from 2012 to 2022
Minpeng HUANG ; Aijun QIAN ; Fajian LUO ; Linfeng GAO
Shanghai Journal of Preventive Medicine 2024;36(6):566-569
ObjectiveThe purpose was to understand the background level of environmental radioactivity in the surrounding area of Qinshan Nuclear Power Plant and accumulate historical monitoring data of radioactivity in the environment, in order to detect and deal with radioactive risk in water sources earlier. MethodsAccording to the requirements of the "Shanghai environmental radioactivity background monitoring plan", the area 1 closest to the Qinshan Nuclear Power Plant was selected as the monitoring point, and the area 2 far from the nuclear power plant was selected as the blank control point. Considering the seasonal characteristics of high water, low water, and normal water periods, the establishment of sampling points, and population density and other comprehensive factors, a model of sampling from the disease control centers in these two regions was established, with the supervision and quality control by Shanghai disease control center. The water samples were collected once a quarter, with a sampling volume of 5 L each time, and the samples were sent to Shanghai Municipal Center for Disease Control and Prevention for processing and measurement. Since 2012, water samples from the two sources have been collected for more than ten years for the total α and total β monitoring of radioactive levels. Results2012‒2022 Area 1 total α radioactivity, total β radioactivity concentration ranges were 1.83×10-2‒3.93 ×10-2 Bq·L-1 and 6.05×10-2‒23.73 ×10-2 Bq·L-1, respectively. Total α radioactivity and total β radioactivity concentration ranges in Area 2 were 1.63×10-2‒4.46 ×10-2 Bq·L-1, and 9.60×10-2‒25.33 ×10-2 Bq·L-1,respectively. ConclusionThe radioactive levels in the source water of Area 1 and Area 2 are within the normal background range, which meets the requirements of the "Standard test methods for drinking water - radioactive indicators" (GB/T 5750.13‒2006).
9.Intercomparison of institutions providing individual external exposure monitoring services in Shanghai from 2021 to 2023
Aijun QIAN ; Xuexin WEN ; Linfeng GAO ; Qiaochu YANGFAN ; Jie YAO ; Minpeng HUANG
Journal of Environmental and Occupational Medicine 2024;41(10):1162-1166
Background The monitoring of external radiation individual doses for radiation workers is a statutory task and serves as an important basis for the diagnosis of occupational diseases in this occupational group. Ensuring the accuracy and reliability of monitoring data is crucial for safeguarding the health of radiation workers. Objective To evaluate and compare the capabilities and levels of external radiation individual dose monitoring conducted by radiation hygiene service institutions in Shanghai, to standardize relevant workflows, and to improve the accuracy and reliability of the monitoring service. Methods From 2021 to 2023, annual intercomparisons of external radiation individual dose monitoring capabilities were organized for radiation hygiene service institutions in Shanghai. The study subjects were 19 to 21 radiation hygiene service institutions registered in Shanghai for each year and they all participated in the intercomparisons. The monitoring subjects included 16 district-level centers for disease control and prevention (CDCs) and 13 third-party testing agencies. Monitoring capabilities were analyzed based on single-group performance, comprehensive performance, and Q-value. In the intercomparison, a thermoluminescent dosimetry system was used to perform irradiation tests on thermoluminescence dosimeter [made of lithium fluoride (magnesium, copper, phosphorus), LiF (Mg, Cu, P)], and monitoring data for X-rays and γ-rays at different doses and radiation conditions were analyzed following a standard procedure specified by GBZ 207−2016. Statistical methods included t-test and Kolmogorov-Smirnov test, with statistical significance set at P<0.05. Results From 2021 to 2023, the number of participating institutions was 19, 21, and 19, respectively, with an overall pass rate of 94.9% (56/59). Two institutions failed in 2022 and one in 2023. The number of institutions meeting the excellent standard in single-group and comprehensive performance was 9, 12, and 13, respectively, and the number of institutions ultimately rated as excellent was 3, 7, and 8,respectively, with an overall excellence rate of 30.5% (18/59) and an excellence conversion rate of 52.9%. The pass rates for single-group and comprehensive performance were both 98.3%. The number of groups with negative deviation was 1.86 times that of groups with positive deviation for X-rays, and 1.10 times for γ-rays. For X-rays, there was a statistically significant deviation between doses of less than 1.0 mSv and more than 1.0 mSv (P=0.01), while there was no significant difference in the single-group performance deviation between X-rays and γ-rays at the same dose. There was a statistically significant difference between the reported and reference values for X-rays in 2021 and 2022 (P<0.05), but no significant difference in 2023 (P>0.05); there was no significant difference between the reported and reference values for γ-rays over the three years (P>0.05). Conclusion Over the past three years, the external radiation individual dose monitoring capability intercomparison results of radiation hygiene service institutions in Shanghai have shown that the pass rate remains at a high level, with the excellence rate increasing year by year. However, some institutions still need to improve their monitoring capabilities, and further cooperation among institutions and training for technical staff are needed to enhance the capabilities and standardization of external radiation individual dose monitoring in Shanghai.
10.Study on the predictive value of the CT pulmonary angiography parameters from the 2022 ESC/ERS guidelines for chronic thromboembolic pulmonary hypertension
Wenqing XU ; Haoyu YANG ; Anqi LIU ; Mei DENG ; Linfeng XI ; Qiang HUANG ; Wanmu XIE ; Min LIU
Journal of Practical Radiology 2024;40(7):1056-1061
Objective To assess the predictive value of computed tomography pulmonary angiography(CTPA)cardiovascular parame-ters for chronic thromboembolic pulmonary hypertension(CTEPH)under the 2022 European Society of Cardiology/European Respiratory Society(ESC/ERS)guidelines,and to compare with the 2021 Chinese guidelines.Methods A total of 201 suspected CTEPH patients were retrospectively selected.All patients underwent right heart catheterization(RHC)and CTPA evaluation.According to the Euro-pean guidelines,they were divided into three groups:mean pulmonary artery pressure(mPAP)≤20 mmHg control group(63 cases)(1 mmHg=0.133 kPa),mPAP>20 mmHg CTEPH group(138 cases),and mPAP≥25 mmHg CTEPH group(123 cases).Inter-group comparison of CTPA cardiovascular parameters was performed,and receiver operating characteristic(ROC)curve analysis was performed for each parameter.Results Under the 2022 European guidelines,the diagnostic efficacy of the diameter of the main pulmonary artery trunk(MPAd)was the highest[area under the curne(AUC)was 0.933].The binary logistic regression analysis revealed that the MP Ad,right ventricular free wall thickness(RVWT),and interventricular septal angle(IVSA)were inde-pendent risk factors for the diagnosis of CTEPH(P<0.05).Under both the Chinese and European guidelines,the MPAd,the transverse diameter and area of the right atrium,the transverse diameter and area of the bi-ventricle,the RVWT,and the IVSA showed significant statistical differences in CTEPH and control groups(P<0.05).Conclusion Under both the Chinese and European guidelines,the MP Ad measured by CTPA has the highest diagnostic efficacy for CTEPH,while the IVSA has the strongest correlation with clinical prognostic indicators.The right atrium structure also has evaluation value.

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