1.Personalized treatment of well-differentiated gastric neuroendocrine tumors based on clinicopathological classification and grading: A multicenter retrospective study
Ju HUANG ; Huimin LIU ; Dekun YANG ; Tianming XU ; Jing WANG ; Jingnan LI
Chinese Medical Journal 2024;137(6):720-728
Background::The incidence of well-differentiated gastric neuroendocrine tumors (G-NET) is increasing annually, and while they have a good prognosis and low mortality rate, their high recurrence rate makes treatment options controversial. This study aims to determine the relationship between individualized treatment plans and the recurrence of G-NET.Methods::We performed a multicenter, retrospective study of 94 patients with highly differentiated G-NET and treated at Peking Union Medical College Hospital, Yantai Yuhuangding Hospital, and Beijing Zhong-Neng-Jian Hospital from November 2015 to September 2023. Risk factors for recurrence of G-NETs were investigated using chi-squared test and multifactorial logistic regression analysis.Results::After a median follow-up of 49 months, the overall recurrence rate among the 94 G-NET patients was 14% (13/94). The recurrence rates of endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), somatostatin analog (SSA) therapy, and surgery were 43% (6/14), 10% (5/49), 5% (1/22), and 11% (1/9), respectively. Post-treatment recurrence rates were significantly different ( P = 0.014) among four treatments (EMR, ESD, SSA, and surgery), and further subgroup comparisons revealed lower recurrence rates in the ESD and SSA groups than in the EMR group. From the second month onward, SSA therapy considerably reduced the gastrin levels from 1081.0 (571.5, 2472.8) pg/mL to 461.5 (255.3, 795.0) pg/mL ( Z = -3.521, P <0.001). Both chi-squared test and multifactorial logistic regression analysis suggested that among the clinicopathological parameters studied, only the pre-treatment gastrin level ( P = 0.018 and 0.005) and the type of treatment ( P = 0.014 and 0.017) were significantly associated with G-NET recurrence. Conclusions::Individualized treatment strategies may reduce the risk of relapse after G-NET treatment. Long-term SSA therapy may be a secure and efficacious treatment option for type 1 G-NET with more than six lesions, and it substantially decreases the incidence of post-treatment recurrence.
2.Observation of mechanism of electroacupuncture on nerve repair in mice with neuropathic pain based on PKC-P2X3 signal pathway
Li WANG ; Shiping CHENG ; Xingqian YI ; Pingsheng ZHOU ; Jing LIU ; Tianming TAO ; Li CHEN
Chinese Journal of Immunology 2024;40(6):1178-1182,1188
Objective:To observe the mechanism of electroacupuncture on nerve repair in mice with neuropathic pain based on the protein kinase C(PKC)-purinergic receptor P2X ligand-gated ion channel 3(P2X3)signal pathway.Methods:A total of 48 mice were randomly divided into sham group,model group,acupuncture group and electroacupuncture group,with 12 mice in each group.Except the sham group,the other mice were constructed with chronic constriction injury(CCI)model.On the 8th day after operation,acupuncture group and electroacupuncture group received acupuncture and electroacupuncture interventions for 7 days.Mechanical withdrawal threshold(MWT)and thermal withdrawal latency(TWL)were measured before operation and 3rd,5th,7th,10th,12th and 14th day after operation.All mice were killed 15 days after operation.The histomorphology of sciatic nerve was ob-served by HE staining.The levels of IL-1β and TNF-α in spinal cord were detected by ELISA.PKC and P2X3 levels in spinal cord tis-sue were detected by Western blot.PKC and P2X3 expressions in spinal cord neurons were detected by Immunofluorescence.Results:In the sham group,the neuronal cells were of different sizes,the cell membrane was intact,the cytoplasm was fine and granular,the nucleus was large and round,and the nucleolus was clearlyvisible in the middle.Atrophic neurons could be seen in the model group,myelinated nerve fibers were disordered,axons were swollen,and spaces were formed between neurons.Compared with the model group,the number of atrophic neurons decreased in the acupuncture group and the electroacupuncture group(P<0.05),the arrange-ment of myelinated nerve fibers improved and the improvement in the electroacupuncture group was more obvious than that in the acu-puncture group.Compared with the sham group at the same time point,on the 3rd,5th,7th,10th,12th and 14th day after opera-tion,the MWT and TWL values of the model group,acupuncture group and electroacupuncture group decreased significantly(P<0.05),while the expressions of IL-1β,TNF-α,PKC,P2X3,the numbers of PKC and P2X3 positive cells and the average optical den-sity increased(P<0.05).Compared with the model group,the values of MWT and TWL in the acupuncture group and electroacupunc-ture group increased significantly on the 10th,12th and 14th day after operation(P<0.05),while the expression of IL-1β,TNF-α,PKC,P2X3,the number of PKC and P2X3 positive cells and the average optical density decreased(P<0.05).Compared with the acu-puncture group,the values of MWT and TWL in the electroacupuncture group increased significantly on the 10th,12th and 14th day after operation(P<0.05),while the expressions of IL-1β,TNF-α,PKC,P2X3,the numbers of PKC and P2X3 positive cells and the average optical density decreased(P<0.05).Conclusion:Electroacupuncture can reduce the neuroinflammatory reaction of CCI model mice,reduce the expression levels of PKC and P2X3,improve the morphology of sciatic nerve cells and the arrangement of myelinated nerve fibers,reduce the gap between neurons,increase the values of MWT and TWL,and relieve the degree of neuropathic pain.
3.Exploration of the Application of Blockchain Technology in the Future Medical Service System
Huan WANG ; Tao LIU ; Jing WANG ; Yanan GAO ; Xin LI ; Liyuan HU ; Zihang FENG ; Zhiyong ZHAO ; Qingyang HUANG ; Quanyu MENG ; Xiaojuan ZHANG ; Hexuan CUI ; Tianming CHEN
Journal of Medical Informatics 2024;45(11):91-94,103
Purpose/Significance To explore the feasibility of applying blockchain technology to the current healthcare system of hos-pitals,and to achieve the purpose of protecting patients'privacy to the greatest extent possible at a lower cost.Method/Process 505 questionnaires are randomly distributed and collected from people of different age groups in Beijing,Tianjin,Shanghai and Shenzhen who have a certain degree of understanding of blockchain technology,and the results are analyzed.Result/Conclusion Different age groups are highly concerned about personal privacy and privacy protection,and are willing to accept blockchain as an emerging technology.There is a greater demand and acceptance for the application of blockchain technology in the primary health care systems.
4.Growth and Development Trend of Lateral Plaques and Subsequent Plaques in Bifurcated Vessels:A Dynamic Simulation
Zhao LIU ; Hao SUN ; Keyi TAO ; Tianming DU ; Yanping ZHANG ; Shengwen LIU ; Jiling FENG ; Aike QIAO
Journal of Medical Biomechanics 2024;39(5):838-845
Objective To investigate vascular remodeling and low-density lipoprotein(LDL)deposition,the growth and development trends of lateral branch plaques in bifurcated vessels,and the potential locations of subsequent plaque growth due to the presence of plaques.Methods An idealized model of bifurcated vessels was established and the distribution of wall shear stress before and after the growth of edge-branch plaques was obtained using computational fluid dynamics.Seven sections were intercepted in the areas of low shear stress:planes 1-3 were the low shear stress areas on the lateral branch before plaque formation,planes 4-5 were the proximal and distal edges of the plaque,and planes 6-7 were the lower shear stress areas of the plaque.Vascular remodeling and LDL deposition in the cross section were simulated.The growth and development trends of plaques are also discussed.Results Among planes 1-3,plane 2 produced obvious negative remodeling and the highest concentration of LDL deposition(102.266 mmol/L),thereby indicating that this was the initial location of the atherosclerotic plaque.Compared to plane 4,plane 5 produced more pronounced vascular remodeling,lumen narrowing,and the highest deposition concentration(110.17 mmol/L)after plaque formation,which indicated that the patch had a tendency for eccentric growth downstream.Compared to plane 6,plane 7(blood flow separation reattachment site)produced more negative remodeling and the highest deposition concentration(93.851 mmol/L),thereby indicating the possibility of new plaque formation near the reattachment point of blood flow separation.Conclusions Obvious vascular remodeling at low shear stress in the lateral branches leads to lumen stenosis and high LDL deposition,thus,forming atherosclerotic plaques.The lateral wall of the bifurcated blood vessels is the initial location of atherosclerotic plaque growth.After growth,the plaque tends to develop downstream,and subsequent plaques may form at the flow separation and reattachment points.
5.Targeting cAMP in D1-MSNs in the nucleus accumbens, a new rapid antidepressant strategy.
Yue ZHANG ; Jingwen GAO ; Na LI ; Peng XU ; Shimeng QU ; Jinqian CHENG ; Mingrui WANG ; Xueru LI ; Yaheng SONG ; Fan XIAO ; Xinyu YANG ; Jihong LIU ; Hao HONG ; Ronghao MU ; Xiaotian LI ; Youmei WANG ; Hui XU ; Yuan XIE ; Tianming GAO ; Guangji WANG ; Jiye AA
Acta Pharmaceutica Sinica B 2024;14(2):667-681
Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.
6.Expert opinions on operation rules of Morita therapy outpatient service
Jiangbo LI ; Zucheng WANG ; Yuhua CUI ; Yingzhi LU ; Weijie QU ; Haiyin ZHANG ; Fuqiang MAO ; Fengqing QIE ; Wanghong SHI ; Qinfeng ZHANG ; Lingyi PAN ; Ling ZHANG ; Jianzhong LI ; Guangcheng CUI ; Tongxian CHEN ; Xiuqing MA ; Wei RONG ; Jianjun ZHANG ; Qingfang ZHONG ; Yanchi ZHANG ; Boquan ZHANG ; Xinrui WANG ; Wenyou MA ; Qingtao REN ; Yongfa JING ; Huanzhong LIU ; Zhenjian YU ; Laitian ZHAO ; Tianming HAN ; Xue HAN
Chinese Mental Health Journal 2024;38(1):68-72
Morita therapy has been bom for more than 100 years.Inpatient Morita therapy is highly oper-able and easy to master.It can improve many refractory neuroses through four-stage treatment.But more neuroses are treated in outpatient clinics,and Morita therapy cannot be used in hospitalized patients.Therefore,the formula-tion of expert opinions on outpatient operations is particularly important.This paper is based on domestic and for-eign references,and after many discussions by domestic Morita therapy experts,and then drew up the first version of the expert opinions on operation of outpatient Morita therapy.Meanwhile the operation rule of Morita therapy in three stages of outpatient treatment was formulated:in the etiological analysis stage,under the theoretical guidance of Morita therapy,analyze the pathogenic factors,to improve treatment compliance and reduce resistance;during the operating stage,guide patients to engage in constructive and meaningful actions,realizing the achievement of letting nature take its course principle;in the cultivating character and enriching life stage,pay attention to positive infor-mation,expanding the scope and content of actions,improving the ability to adapt to complex life,and preventing recurrence caused by insufficient abilities.It will lay a foundation for the promotion of Morita therapy in domestic outpatient clinics,so that more patients with neurosis and other psychological diseases could receive characteristic Morita therapy treatment in outpatient clinics.
7.Potential application value of FilmArray ? meningitis/encephalitis panel in children with suspected central nervous system infections
Xue NING ; Muhan LI ; Xin GUO ; Huili HU ; Lingyun GUO ; Bing HU ; Tianming CHEN ; Gang LIU
Chinese Journal of Applied Clinical Pediatrics 2024;39(7):519-522
Objective:To explore the clinical application and effect of FilmArray ? meningitis/encephalitis (ME) panel in identifying pathogens of central nervous system (CNS) infections in children. Methods:Molecular biology study.Cerebrospinal fluid (CSF) samples were prospectively obtained through lumbar puncture from children with suspected CNS infections admitted to the Department of Infectious Diseases at Beijing Children′s Hospital, Capital Medical University from May to November 2019.These samples were subjected to both routine clinical pathogen testing and FilmArray ME panel testing.Polymerase chain reaction was used to validate all samples.Independent sample t-test or Mann-Whitney U-test was used for comparative analysis of the results and influence factors obtained by the two detection methods. Results:A total of 113 cases of suspected CNS infections were enrolled.Routine clinical testing yielded 17 cases, with a positive rate of 15.0%, including 4 positive CSF cultures, with a positivity rate of 3.5%.FilmArray ME panel detected 23 positive cases, with a positive rate of 20.4%.FilmArray ME panel detected bacteria in 7 cases, viruses in 13 cases, fungi in 1 case, and both viruses and bacteria in 2 cases.Among the common pathogens detected, FilmArray ME panel obtained the results on average 2.7 days in advance.Conclusions:Compared with CSF culture, FilmArray ME panel has the advantages of shorter detection period, higher positive detection rate, and higher virus detection rate.
8.A multicenter study on the effects of congenital cytomegalovirus infection on hearing loss
Bofei HU ; Xinxin LIU ; Canyang ZHAN ; Tianming YUAN ; Lihua CHEN ; Jianfeng LIANG ; Jing SUN ; Meifang LIN ; Man HE ; Suling WEI ; Jiening ZHANG ; Jiajun ZHU ; Yinghu CHEN
Chinese Journal of Pediatrics 2024;62(8):721-726
Objective:To assess the clinical features and effectiveness of antiviral therapy in newborns with sensorineural hearing loss (SNHL) caused by congenital congenital cytomegalovirus (cCMV) infection, and to speculate the risk factors for poor hearing outcomes.Methods:A multicenter prospective cohort study wasconducted, enrolling 176 newborns diagnosed with cCMV at four research centers in Zhejiang Province from March 1, 2021, to April 30, 2024. Clinical characteristics at birth were recorded and hearing was followed up. The children were divided into groups based on their condition at birth, specifically into asymptomatic, mild symptom, and moderate to severe symptom groups. Additionally, they were divided into SNHL and normal hearing groups based on the results of air conduction brainstem audiometry at birth. And they were also divided into treatment and untreated groups according to antiviral treatment. Mann Whitney U test, and chi square test were used for inter group comparison to analyze the differences in clinical features between different disease groups, and to analyze the effects of clinical features, antiviral therapy, and other factors on hearing improvement. Logistic regression analysis was employed to identify the risk factors influencing hearing outcomes. Results:Among the cohort of 176 children diagnosed infection with cCMV, 90 cases were male and 86 cases were female. Of these, 79 cases were asymptomatic, 12 cases classified as mild cCMV and 85 cases as moderate to severe cCMV. Fifty cases belonged to SNHL group, with different degrees of severity, including 30 cases of mild, 9 cases of moderate, 5 cases of severe, and 6 cases of extremely severe SNHL. Among the 121 cases in the normal hearing group, 2 cases (1.7%) exhibited late-onset hearing loss despite having normal hearing at birth. Among 81 cases (46.0%) who completed the hearing follow-up, 71 cases (87.7%) had good hearing outcomes and 10 cases (12.3%) had poor hearing outcomes. Among the 81 children, 29 cases (35.8%) had SNHL at birth. During follow-up, the hearing threshold improved in 19 cases (65.5%), remained stable in 7 cases (24.1%) and progressed in 3 cases (10.3%). A total of 26 cases in the treatment group and 55 cases in the untreated group completed the hearing follow-up assessment. The rate of hearing improvement in the treatment group was found to be higher compared to the untreated group (13 cases (50.0%) vs. 6 cases (10.9%), χ2=15.00, P<0.01), with individuals in the treatment group having a 4.58 times greater likelihood of experiencing hearing improvement ( RR=4.58,95% CI 1.96-10.70, P<0.05). However, no statistically significant difference was observed in hearing outcomes between the antiviral treatment group and the untreated group ( RR=0.90, 95% CI 0.57-1.41, P=0.517). Multivariate analysis further confirmed SNHL ( OR=11.58, 95% CI 2.10-63.93, P=0.005) and preterm birth ( OR=4.98, 95% CI 1.06-23.41, P=0.042) as independent risk factors for poor hearing outcomes. Conclusions:SNHL resulting from cCMV infection presents symptoms at birth and can be improved by antiviral therapy. Poor hearing outcomes are associated with SNHL and prematurity.
9.Mechanism of Glycyrrhizae Radix et Rhizoma Alleviating Tripterygium wilfordii Polyglycoside Tablets-induced Liver Injury
Minghong ZHAO ; Tianming LU ; Li LIU ; Qixin WANG ; Tong YANG ; Na LIN ; Chong QIU ; Tianyu ZHONG ; Qiuyan GUO ; Jigang WANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(5):24-31
ObjectiveTo investigate the protective effect of cytochrome P4502D6 (CYP2D6) and cytochrome P4503A4 (CYP3A4), key enzymes of drug metabolism in liver, on acute liver injury in water extract of Glycyrrhizae Radix et Rhizoma (WEOGRR). MethodHealthy male Kunming mice were divided into normal group, model group, WEOGRR low-, medium- and high-dose groups (5, 10, 15 g·kg-1·d-1) and positive drug group (diammonium glycyrrhizinate, 75 mg·kg-1·d-1), with 10 in each group. One week after preventive administration, acute liver injury model was induced by single intragastric administration of 270 mg·kg-1 Tripterygium Glycosides tablets, and samples were collected after 18 h. The pathological changes of liver were observed by hematoxylin-eosin (HE) staining. Serum liver function indexes including alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptadase (γ-GT), alkaline phosphatase (ALP), and total bilirubin (TBIL) as well as the levels of oxidative stress indexes including malondialdehyde (MDA) and superoxide dismutase (SOD) in hepatocytes were determined by biochemical method. Real-time polymerase chain reaction (Real-time PCR) and Western blot were performed to detect the mRNA and protein expression levels of CYP2D6 and CYP3A4, respectively. ResultCompared with normal group, model group had significant hepatocyte swelling and inflammatory cell infiltration (P<0.01), increased AST, ALT, γ-GT, ALP and TBIL (P<0.05), elevated MDA and decreased SOD (P<0.01) as well as down-regulated mRNA and protein expression levels of CYP2D6 and CYP3A4 (P<0.05). Compared with the model group, the normal group had intact liver structure without obvious abnormality, and the WEOGRR groups and positive drug group presented alleviated hepatocyte swelling and inflammatory cell infiltration (P<0.01), reduced AST, ALT, γ-GT, ALP and TBIL (P<0.01), lowered MDA and increased SOD (P<0.01) as well as up-regulated expression levels of CYP2D6 and CYP3A4 (P<0.01). ConclusionThe protective effect of WEOGRR on acute liver injury induced by Tripterygium glycosides tablets may be related to reducing the contents of AST, ALT, γ-GT, ALP and TBIL in serum, inhibiting MDA and increasing the activity of SOD in liver cells, and enhancing the activities of CYP2D6 and CYP3A4, thus accelerating the metabolism of toxic substances.
10.Clinical prediction model for complicated appendicitis in children under five years old
Tianming WANG ; Guoqin ZHANG ; Tingjun LI ; Jiahu HUANG ; Zhagen WANG ; Huiwen TANG ; Zhujun GU ; Jian LIU ; Xingyuan LIU
Chinese Pediatric Emergency Medicine 2023;30(4):286-290
Objective:To retrospectively analyze the independent risk factors of complicated appendicitis(CA)in children under five years old and establish a clinical prediction model, and to evaluate the clinical application of this model.Methods:A retrospective analysis was performed on children under five years old who underwent appendectomy at Children′s Hospital of Shanghai Jiao Tong University School of Medicine from January 2018 to December 2021.The children were divided into CA group and uncomplicated appendicitis group according to whether there was sign of perforation or gangrene in appendiceal tissue after operation.The differences in clinical features and preoperative laboratory test results between two groups were compared.The independent risk factors of CA were identified and a clinical prediction model was established.The clinical prediction model was verified by receiver operating characteristic curve.Results:A total of 140 children were enrolled in this study, including 84 cases in the CA group and 56 cases in uncomplicated appendicitis group.Univariate and binary Logistic regression analysis showed that the duration of symptoms>23.5 h( OR=6.650, 95% CI 2.469-17.912, P<0.05), abdominal muscle tension( OR=3.082, 95% CI 1.190-7.979, P<0.05) and C-reactive protein>41 mg/L ( OR=3.287, 95% CI 1.274-8.480, P<0.05) were independent risk factors for CA( P<0.05). The clinical prediction model of CA was constructed by the above mentioned three independent risk factors.The area under the receiver operating characteristic curve of the clinical prediction model was 0.881(95% CI 0.825-0.936), the sensitivity was 77.4%, the specificity was 87.5%, the positive predictive value was 91.3% and the negative predictive value was 70.0%. Conclusion:Acute appendicitis in children under five years old is more likely to progress to CA if the duration of symptoms>23.5 h, the level of C-reactive protein is increased, and the abdominal muscle tension is accompanied.The clinical prediction model of CA constructed by common clinical information in pediatric clinics has good prediction efficiency, which provides a simple and feasible reference method for clinicians to distinguish CA from uncomplicated appendicitis.

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