1.Treatment of Sepsis-induced Inflammatory Responses with Xijiao Dihuangtang by Modulation of PKM2-mediated One-carbon Metabolism Pathway
Qixiang YAN ; Yeyan ZHU ; Fan GE ; Qimeng SUN ; Leyao YE ; Fang TIAN ; Jun LU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(10):18-26
ObjectiveTo investigate the effects of Xijiao Dihuangtang (XJDHT) on mice with sepsis and cellular models of sepsis and explore its molecular mechanism in alleviating sepsis-induced inflammatory responses via regulating pyruvate kinase M2 (PKM2)-mediated one-carbon metabolism pathway. MethodsForty C57BL/6N mice were randomly divided into four groups: normal group, model group, low-dose XJDHT group (7.7 g·kg-1), and high-dose XJDHT group (15.4 g·kg-1). After one week of continuous gavage, sepsis was induced using cecal ligation and puncture (CLP) in groups except the normal group. 24 h after the surgery, mortality rates in all groups were recorded, and serum cytokines were measured by enzyme linked immunosorbent assay (ELISA). Lung histopathology was examined by hematoxylin-eosin (HE) staining. During the in vitro experiment, the human monocytic leukemia cell line (THP-1) was exposed to various concentrations of XJDHT and treated with lipopolysaccharide (LPS) at a final concentration of 2 mg·L-1 for 24 h. Cell apoptosis was detected using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Protein levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), B-cell lymphoma 2 (Bcl-2), and Bcl-2-associated X protein (Bax) were measured by Western blot. Transcriptome sequencing was performed to analyze differentially expressed genes in all groups and conduct gene ontology (GO) enrichment. Key genes in the one-carbon metabolism pathway, including pyruvate kinase M2 (PKM2), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR), and phosphoglycerate dehydrogenase (PHGDH), were verified by Western blot. A PKM2 inhibition model was established using shikonin for further protein expression analysis. ResultsAnimal experiments showed that compared with the normal group, the model group exhibited significantly elevated body temperature and lung pathology (P<0.01) and increased serum TNF-α and IL-1β levels (P<0.01). High-dose XJDHT reduced body temperature and lung tissue damage (P<0.01) and significantly decreased serum TNF-α and IL-1β levels (P<0.01). Low-dose XJDHT treatment showed no significant temperature change (P<0.01) but reduced serum TNF-α and IL-1β levels (P<0.01). Transcriptome sequencing and Western blot revealed significant differences in the expression of TNF-α, IL-1β, and one-carbon metabolism genes (PKM2, MTR, and PHGDH) (P<0.01). Cell experiments demonstrated that compared to the normal group, the model group showed elevated protein expressions of TNF-α and IL-1β in THP-1 cells (P<0.01), decreased Bcl-2/Bax ratio, and increased apoptosis (P<0.01). Transcriptome sequencing and Western blot revealed significant differences in the expression of TNF-α, IL-1β, and one-carbon metabolism genes (PKM2, MTR, and PHGDH) (P<0.01). Compared to the model group, high-dose XJDHT significantly increased Bax/Bcl-2 ratio and PHGDH protein expression (P<0.01) and effectively reduced cell apoptosis (P<0.01) while down-regulating protein expressions of TNF-α, IL-1β, PKM2, and MTR (P<0.01). Low-dose XJDHT moderately increased Bax/Bcl-2 ratio and PHGDH protein expression (P<0.05), reduced apoptosis (P<0.05), and decreased IL-1β and MTR protein levels (P<0.05, P<0.01), but there were no significant changes in TNF-α and PKM2 expression. After PKM2 inhibition by shikonin in THP-1 cells, the expression of protein related to one-carbon metabolism was detected. Compared with the blank group, the LPS-induced model group showed significantly upregulated PKM2 and MTR protein expression (P<0.01) and downregulated PHGDH expression (P<0.01). Compared with the model group, shikonin treatment significantly reduced PKM2 expression (P<0.05), increased PHGDH expression (P<0.01), and decreased MTR expression (P<0.05). ConclusionXJDHT can inhibit the release of inflammatory factors in sepsis, and its mechanism is related to the intervention of the PKM2-regulated one-carbon metabolism pathway in macrophages.
2.Analysis on current situation of drug use in Chinese aeromedical rescue
Aobo LI ; Wei WANG ; Yanrong ZHU ; Chunyan XIN ; Chen LI ; Xu GE
China Pharmacy 2025;36(9):1035-1039
OBJECTIVE To analyze the current situation of drug use in domestic aeromedical rescue, and provide references for the development of aeromedical rescue services and the rational use of drugs on board. METHODS All literature on aeromedical rescue in China were retrieved from the databases of SinoMed, CNKI, VIP, and Wanfang data up to September 1st, 2024. Extracting descriptive analysis were conducted on the literature screened by the inclusion and exclusion criteria. RESULTS A total of 36 literature were included. Aeromedical rescue cases had been reported in China since 1985, with a cumulative total of 5 370 cases reported. Prehospital rescue performed 861 cases, with 96.40% of them involving the use of at least 9 categories, totaling at least 10 different drugs, primarily emergency drugs. Interhospital rescue performed 4 509 cases, and 85.23% of them used over 48 kinds of drugs across 19 categories, mainly emergency drugs supplemented by specialty drugs. From the view of transportation, 5 166 air transfers were made by helicopters, of which 88.00% involved the use of drugs, and 204 cases by fixed-wing aircraft, of which 91.18% involved the use of drugs. CONCLUSIONS Drugs are frequently used in aeromedical rescue involving a wide variety of types in China. It is imperative to strengthen the focus on the equipment and rational use of drugs in aeromedical rescue, thereby facilitating the establishment of a standardized theoretical framework.
3.STAR Guideline Terminology(Ⅱ): Clinical Question Formulation, Evidence Retrieval and Appraisal, and Recommendation Development
Di ZHU ; Haodong LI ; Zijun WANG ; Qianling SHI ; Hui LIU ; Yishan QIN ; Yuanyuan YAO ; Zhewei LI ; Hongfeng HE ; Jinhui TIAN ; Long GE ; Yaolong CHEN ;
Medical Journal of Peking Union Medical College Hospital 2025;16(3):756-764
To introduce and analyze guideline terminology related to clinical question formulation, evidence retrieval and appraisal, and recommendation development. A systematic search was conducted in guideline development manuals and relevant methodological literature, covering publications up to October 25, 2024. Terminology related to the three aforementioned stages of related to guideline development was extracted from the included literature, standardized, and refined through consensus meetings to finalize a comprehensive terminology list and definitions. A total of 30 guideline development manuals and 15 methodological articles were included, and 23 core terms were identified. It is recommended to develop a standardized and scientifically sound guideline terminology system with unified naming, clear definitions, and alignment with the linguistic environment and usage habits in China. At the same time, it is essential to strengthen terminology training for both guideline developers and users based on this system, in order to deepen their correct understanding and proper application of guideline terminology.
4.Study on the current status of emergency management for severe mental disorders in Shanghai
Xiaolei GE ; Yi ZHU ; Chunmei CHEN ; Youwei ZHU ; Yanli LIU ; Jun CAI ; Weibo ZHANG ; Fei XIE
Shanghai Journal of Preventive Medicine 2025;37(3):276-281
ObjectiveTo investigate the current status of emergency management for severe mental disorders in Shanghai, and to provide countermeasures and suggestions for the establishment of a sound emergency management system for severe mental disorders and the enhancement of emergency management capability. MethodsA questionnaire survey and qualitative interviews were used to conduct an investigation into the emergency management in 17 district-level mental illness prevention and control institutions in Shanghai, which includes the basic situation of emergency management for severe mental disorders, the construction of emergency response teams and personnel, emergency preparedness drills and training, emergency management plans and rules and regulations, and problems encountered in emergency management. ResultsIn terms of emergency management mechanism and basic situation, resources such as personnel allocation, security funds and green channel were well equipped in each district-level mental illness prevention and control institution in Shanghai. However, the equipment of some hardware facilities was still insufficient to some extent. Therefore, further improvement on the emergency management mechanism for severe mental disorders was needed. With regard to the construction of emergency team and personnel allocation, the majority were those aged between 35‒<45 years old, with a bachelor’s degree, and more than 10 years of working experience. For example, 90.27% staff in district-level mental illness prevention and control institution had a bachelor’s degree or above, which was higher than that among the staff in community-level (73.60%); staff majored in clinical medicine in district-level institution accounted for the proportion at 52.71%, higher than that among the staff in community-level (28.86%); 57.24% staff in district-level institution had an intermediate professional title, higher than that among the staff in community-level (42.28%); and 69.90% staff in district-level institution had more than 10 years of working experience, higher than that among the staff in community-level (43.62%). In the aspect of emergency drills and training, all district-level mental illness prevention and control institutions in Shanghai had a high demand for emergency training, and the weak aspects mainly focused on lack of emergency service protocols, skills of addressing technical challenges, and construction of effectiveness evaluation system. Moreover, the teaching methods were primarily centered on case analysis, simulation drills, interactive discussions, and so forth. Concerning emergency management plans and rules and regulations, all districts in Shanghai had relatively established well-developed systems for emergency response plans, emergency response leadership groups, and emergency response operational task forces for severe mental disorders. About half of the institutions had established other rules and regulations related to emergency management of severe mental disorders in addition to emergency plans. ConclusionShanghai has initially established an emergency management system for severe mental disorders, but it is still fragile in specialized training for emergency management of severe mental disorders, construction of emergency management mechanisms, and the building-up of grassroots emergency teams. Further priorities should include strengthening emergency management training, enhancing the construction of emergency management personnel teams, and gradually establishing a more comprehensive and integrated emergency management mechanism for severe mental disorders.
5. Effects of low concentration atropine on macular microcirculation in children with different degrees of myopia
Wei GE ; Wenyan SHENG ; Qibin XU ; Liwei ZHU ; Qiushi LI
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(3):303-309
AIM: To investigate the effects of 0.01% atropine eye drops on macular blood flow density and retinal thickness in children with different degrees of myopia. METHODS: This was a prospective case-control study. Sixty-four patients (112 eyes) diagnosed with myopia for the first time with 0.01% atropine eye drops before and 6 months after medication were investigated with the uncorrected distance visual acuity (UCVA), axial length (AL), spherical equivalent (SE), macular ganglion cell-inner plexiform layer thicknes (mGCIPL) using slit lamp examination and optical coherence tomography (OCT), vascular density in the macular area and the area of the avascular in the fovea using optical coherence tomography angiography (OCTA) . Changes in various indicators before and after medication were compared. RESULTS: Compared with before medication, the AL of the three groups of myopia patients increased significantly (P<0.01), the difference in low to moderate myopia group was significantly smaller than that in high myopia group. Compared with before medication, SE increased in all three groups of myopia patients, yet there was no statistically significant difference in the low - grade myopia group (P>0.05). The difference was statistically significant between the moderate myopia group and the high myopia group (P< 0.01). Compared with before medication, there was no change in intraocular pressure (IOP) among the three groups of myopic patients (P>0.05). After 6 months of medication, the central circle macular vessel density (cCVD) increased in the low myopia group and moderate myopia group (P<0.01), there was no statistically significant difference in the high myopia group (P>0.05). Before and after medication, there was no significant difference in outer circle macular vessel density (oCVD), inner circle macular vessel density (iCVD), and whole circle macular vessel density (wCVD) among the three myopia groups (P>0.05). The increase in mGCIPL was statistically significant in the low myopia group (P<0.01), but there was no statistically significant difference in the moderate myopia and high myopia groups (P>0.05). There was no significant difference in foveal avascular zone (FAZ) among the three myopia groups before and after medication (P>0.05). There was no correlation between CVD, AL, and SE in the three myopia groups (P>0.01). There was a low correlation between CVD and mGCIPL in the low myopia group (r=0.442, P<0.05), there was no correlation between CVD and mGCIPL in the moderate myopia and high myopia groups (P >0.01). CONCLUSION: 0.01% atropine can significantly reduce the rate of axial and refractive growth in children with low to moderate myopia, increase the density of central macular vessels, and increase the thickness of mGCIPL in children with low to moderate myopia.
6.Analysis of cases of reinfection of past SARS-CoV-2 patients in Pudong New Area of Shanghai
Ge ZHANG ; Anran ZHANG ; Yilin JIA ; Li ZHANG ; Lipeng HAO ; Hongmei XU ; Yuanping WANG ; Chuchu YE ; Bo LIU ; Weiping ZHU ; Yixin ZHOU
Shanghai Journal of Preventive Medicine 2024;36(2):117-122
ObjectiveTo identify the rate, population characteristics, and vaccination history of repeat infections among previously infected people in the current epidemic based on the rate of repeat infection and population characteristics of different mutant strains at different times in Pudong New Area of Shanghai, and to provide reference for the prevention and control strategies of novel coronavirus repeat infections. MethodsA total of 9 250 investigated subjects were randomly selected from the new cases of asymptomatic infection and confirmed cases reported by Pudong New Area from March to May 2022. The investigation mainly focused on demographic characteristics, nucleic acid or antigen test results, and symptoms after infection. The repeat infection rates among different populations were compared, and logistic regression was used to analyze the impact of gender, age, and vaccination status on repeat infections. ResultsThe survey sample of 9 250 people had a response rate of 81.85%. There were 4 043 males (53.40%) and 3 528 females (46.60%), with a median age of 34 years old (P25, P75: 7, 61). The overall vaccine uptake rate was 59.44% (4 500/7 571). In December of 2022, there were 563 cases of repeat infection, with an infection rate of 7.44%. The lowest rate of repeat infection was seen in the 3‒ year-old group (2.86%) and the highest rate in the 30‒ year-old group (12.42%), with significant differences between different age groups. The repeated infection rate for those who had completed their vaccinations was significantly lower (6.57%) compared to those who had not (7.11%). The age groups of 3‒ years, 70‒79 years, as well as individuals who completed full vaccination and received booster shots were protective factors against repeat infections. ConclusionThe overall rate of reinfection among the infected in Shanghai during the spring of 2022 was low in the outbreak of the Omicron variant, and the rate of reinfection in the 3‒ year-old group was significantly lower than in other age groups. Completing the full course of vaccination significantly reduces the risk of reinfection. Although the reinfection rate is high in individuals who received booster shots, it remains a mitigating factor compared to those who do not receive the vaccine. It is recommended to continue monitoring reinfections in key populations and further strengthen immunization efforts.
7.Analysis on the current situation and influencing factors of occupational burnout among bus drivers in Wuhu City
Yue CUI ; Yuhua SHEN ; Fang WANG ; Wenli ZHU ; Wenjing GE
Journal of Shenyang Medical College 2024;26(2):141-145
Objective:To investigate the current situation of occupational burnout among bus drivers in Wuhu City and analyze its influencing factors.Methods:A survey was conducted in 1 388 bus drivers in Wuhu City from Sep to Nov 2022 using the general information questionnaire,the Maslach Burnout Inventory-General Survey(MBI-GS),and the Pittsburgh Sleep Quality Index(PSQI).Multivariable logistic regression analysis was used to analyze the influencing factors of occupational burnout in bus drivers.Spearman correlation analysis was used to analyze the correlation between occupational burnout and sleep quality.Results:Among 1 388 bus drivers,642(46.3%)were positive for occupational burnout,and 139(10.0%)were found to have sleep disorders.Multivariable logistic regression analysis showed that longer bus driving experience(OR=1.873,95%CI:1.325-2.648),lower monthly income(OR=0.376,95%CI:0.158-0.774),higher smoking frequency(OR=1.313,95%CI:1.188-2.163),higher drinking frequency(OR=1.342,95%CI:1.018-1.769),lower weekly physical exercise frequency(OR=0.367,95%CI:0.243-0.555),and poor sleep quality(OR=13.110,95%CI:7.284-23.594)were the influencing factors of bus driver occupational burnout(P<0.05).Spearman correlation analysis showed that the total score of occupational burnout and its dimension scores were positively correlated with the total score of sleep quality and its dimension scores(rs=0.12-0.83,P<0.01).Conclusion:The problem of occupational burnout among bus drivers in Wuhu City is relatively serious,and a part of people have sleep problems,which should be paid great attention to and active measures should be taken in time.
8.Postnatal age-related change of brain volume and its association with neurobehavior outcome in term neonates
Yuying FENG ; Linlin ZHU ; Pengxuan BAI ; Yao GE ; Miaomiao WANG ; Congcong LIU ; Xianjun LI ; Jian YANG ; Chao JIN
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(1):133-138
Objective To analyze the relationship of the volume of 87 brain regions with postnatal age and neurobehavior in full-term neonates.Methods A total of 75 full-term newborns[gestational age(39.38±1.22)weeks;male/female(51/24);postnatal age(11.11±6.67)days]without abnormalities on brain MRI(three-dimensional T1-weighted imaging,3D T1WI)at our hospital between November 2010 and September 2017 were retrospectively included.Based on the template of 87 brain regions,the neonatal brains were divided into 87 brain regions and their volumes were calculated by using V-shape Bottleneck network(VB-Net)deep learning segmentation technique,Pearson partial correlation and regression analysis were used to explore the relationship of the volume of each brain region with postnatal age and neurobehavioral scores.Results After adjusting for gestational age,birth weight,head circumference,body length and sex,66.7%of the regional brain volumes(58/87 brain regions)significantly increased with the postnatal age(correlation coefficient r:0.2-0.7,P<0.05).The volumes of gray matter in bilateral lentiform nucleus,left caudate nucleus,right occipital lobe,right inferior temporal lobe,and bilateral anterior temporal lobe strongly correlated with the postnatal age(r>0.50,P<0.05).The gray matter volume of the right occipital lobe linearly increased with age(slope:100.67),and was positively correlated with behavioral scores(r=0.324,P<0.01).Conclusion Most of regional brain volumes increase with the postnatal age during the neonatal period,and the fastest growth occurs in primary sensorimotor-related brain regions,presenting the spatial heterogeneity.Partial brain region grows with the development of behavioral ability.
9.Celecoxib inhibits thrombin-induced chondrocyte degeneration in rats
Zhiheng ZHU ; Jiaying DING ; Yangshuo GE ; Chunmeng HUANG ; Jun SHEN ; Xuezong WANG ; Yuxin ZHENG ; Daofang DING
Chinese Journal of Tissue Engineering Research 2024;28(34):5446-5451
BACKGROUND:The content of serum thrombin in patients with osteoarthritis is significantly higher than that in normal individuals,and thrombin can induce inflammatory degeneration of rat chondrocytes,suggesting that inhibiting the function of thrombin may become a method for treating osteoarthritis.Celecoxib is a common therapeutic drug for the clinical treatment of osteoarthritis.It is not yet known whether it improves chondrocyte degeneration by inhibiting the activity of thrombin. OBJECTIVE:To investigate the effect of celecoxib on thrombin-induced degeneration of rat chondrocytes. METHODS:Thrombin levels in the serum of osteoarthritis patients and normal individuals were detected by an ELISA kit.Primary chondrocytes of neonatal Sprague-Dawley rats were isolated,and all experiments were performed with cells from passage one.Chondrocytes were randomly divided into three groups:control group,thrombin group,and celecoxib group.The cell morphology of the three groups was observed under an inverted microscope,and an Edu kit was used to detect the cell proliferation.qRT-PCR was used to detect the expression of extracellular matrix components(aggrecan,elastin,cartilage oligomeric matrix proteins),inflammatory factors(interleukin-1,interleukin-6,and tumor necrosis factor-α),and chemokines(monocyte chemotactic protein 2,monocyte chemotactic protein 7,granulocyte chemotactic protein 6).The expression of type 2 collagen α1 was detected by immunofluorescence.Western blot method was used to detect the expression of catabolic metabolism genes,such as matrix metalloproteinase 9,matrix metalloproteinase 13,and cyclooxygenase 2. RESULTS AND CONCLUSION:Patients with osteoarthritis had higher levels of thrombin in the serum compared with normal individuals.Under the microscope,celecoxib was found to significantly inhibit fibroid changes in chondrocytes.Compared with the thrombin group,celecoxib inhibited the proliferation of chondrocytes.The downregulation of extracellular matrix gene expression,such as type II collagen α1,in the thrombin group was inhibited by celecoxib(P<0.05).Thrombin promoted the expression of inflammatory factors(interleukin-1,interleukin-6,and tumor necrosis factor-α),chemokines(monocyte chemotactic protein 2,monocyte chemotactic protein 7,granulocyte chemotactic protein 6),as well as catabolic genes(matrix metalloproteinase 9,matrix metalloproteinase 13,and cyclooxygenase 2),and under the intervention of celecoxib,the expression of these genes could be downregulated(P<0.05).Overall,these findings indicate that celecoxib inhibits the pro-inflammatory effects of thrombin and thereby ameliorates chondrocyte degeneration in rats.
10.Establishment of a safe disposal management program for home used sharp wastes from insulin injection among diabetic patients
Wenjie ZHANG ; Haiying ZHU ; Juan GE ; Yuqin HAN ; Limei ZHENG ; Ruihong LI
Modern Clinical Nursing 2024;23(1):70-77
Objective To establish a safe disposal management program for home used sharps waste of insulin injection so as to provide a reference for the standardised management of sharps waste after insulin.injection.Methods Based on the model of information-motivation-behavioural skills,the safe disposal management program for insulin needles used at home was developed by literature reviews and semi-structured interviews to investigate the perceptions and requirements of patients.The program was then modified and refined by two rounds of expert consultation with Delphi method.Results The effective retrieval rates of questionnaire for two rounds of expert consultations were 88.89%and 93.75%,with an expert authority coefficient at 0.93.In the second round,the mean importance scores of the items were 4.40 to 5.00,with a coefficient of variation ranged from 0 to 0.168.The established program consisted of three primary items,six secondary items,and 20 tertiary items.Conclusion The safe disposal management program for home used sharps waste of insulin injection established from the perspectives of information,motivation and behavioural skills was scientific and practical,which offered a guidance to healthcare professionals in the clinical practices.

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