1.Hepatic T cell subtypes and functional analysis among alveolar echinococcosis patients using single-cell RNA sequencing
Si CHEN ; Xiangqian WANG ; Wanzhong JIA ; Qigang CAI ; Xueyong ZHANG ; Qiang ZHANG ; Haibo ZHENG ; Linghong ZHU ; Bing LI ; Wei WANG ; Xiumin HAN
Chinese Journal of Schistosomiasis Control 2024;36(5):481-493
Objective To investigate T cell subtypes and their functions in liver immune microenvironments among patients with alveolar echinococcosis (AE) using single-cell RNA sequencing (scRNA-seq). Methods Four AE patients that were admitted to Qinghai Provincial People’s Hospital in 2023 for hepatic surgery for the first time were enrolled, and liver specimens were sampled 1 cm (peri-lesion, PL group) and > 5 cm from AE lesions (distal lesion, DL group) among each patient. Finally, a total of eight liver specimens were sampled from four AE patients for scRNA-seq analysis. Genome and transcriptome data of liver specimens were processed using the software Cell Ranger and R package. Differentially expressed genes (DEGs) and their biological functions were analyzed using gene ontology (GO) enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis, and the primary intercellular communication patterns and interaction mechanisms were identified among T cell subtypes in liver specimens using the CellChat package. In addition, the developmental stages of T cells were subjected to trajectory analysis with the monocle package to investigate the expression of genes associated with cell growth and tumor transformation, and to predict the developmental trajectories of T cells. Results All four AE patients were female, with a mean age of (25.00 ± 9.06) years, and there were three cases from Jiuzhi County, Golog Tibetan Autonomous Prefecture and one case from Chengduo County, Yushu Tibetan Autonomous Prefecture, Qinghai Province. The viability of single-cell samples from eight liver specimens was 90.41% to 96.33%, and a total of 81 763 cells were analyzed, with 19 cell types annotated. Of these cell types, 13 were immune cells (87.60%), and T cells (33.13%), neutrophils (15.40%), and natural killer cells (11.92%) were the three most common cell types. Re-clustering of 27 752 T cells and proliferative T cells identified 10 distinct T cell subtypes, with CD8+ cytotoxic T cells (23.43%), CD8+ naive T cells (12.80%), and CD4+ effector memory T cells (17.73%) as dominant cell types. The proportions of T helper 2 (Th2) cells (5.19% vs. 3.63%; χ2 = 38.35, P < 0.01) and CD4+ effector memory T cells (21.59% vs. 13.67%; χ2 = 244.70, P < 0.01) were significantly higher in liver specimens in the PL group than in the DL group, and the proportion of CD4+ helper T cells was significantly lower in the PL group than in the DL group (7.50% vs. 14.75%; χ2 = 330.52, P < 0.01). KEGG pathway analysis revealed that Th2 cells were significantly enriched in cell apoptosis and multiple cancer-associated pathways, and CD4+ effector memory T cells were significantly enriched in the regulation of cytokines and chronic inflammation, while CD4+ helper T cells were significantly enriched in immune responses regulation. Trajectory analysis of T cells showed that CD4+ helper T cells were at an earlier developmental stage relative to Th2 cells and CD4+ effector memory T cells, and the expression of inhibitor of DNA binding 3 (ID3), thioredoxin interacting protein (TXNIP), Bcl2-associated athanogene 3 (BAG3) and heat shock protein family B (small) member 1 (HSPB1) genes appeared a tendency towards a decline over time. Conclusions CD4+ effector memory T cells and CD8+ cytotoxic T cells are primary interacting cells in the liver specimens of AE patients. Reduced expression of Th2 cells and CD4+ helper T cells contributes to an inhibitory immune microenvironment, which promotes immune evasion by Echinococcus multilocularis, and Th2 cells are significantly enriched in multiple cancer-associated pathways, which may be linked to the invasive growth of E. multilocularis.
2.Clinical efficacy of neoadjuvant immunochemotherapy versus neoadjuvant chemotherapy for local advanced gastric adenocarcinoma
Lei WANG ; Linghong WAN ; Tao WANG ; Zhongyi QIN ; Fan LI ; Wenkang LIU ; Bin WANG
Journal of Army Medical University 2024;46(20):2313-2321
Objective To evaluate the therapeutic efficacies of neoadjuvant immunochemotherapy (NAIC )and neoadjuvant chemotherapy (NAC )for local advanced gastric adenocarcinoma and analyze the clinicopathological characteristics.Methods A retrospective cohort study was conducted on 243 patients with locally advanced gastric cancer admitted in Army Medical Center of PLA (Daping Hospital)and the First Affiliated Hospital of China Medical University from January 2017 to July 2023. After balancing the confounding factors by inclusion and exclusion criteria and propensity score matching (PSM),the tumor pathological regression (TRG)rate and safety of the 2 neoadjuvant treatment regimens were analyzed,and the clinical pathological characteristics were analyzed to find clinical pathological characteristics related to efficacy.Results After using PSM to balance the baseline characteristics of the 2 groups of patients,53 subjects in each group were included in the analysis.In terms of TRG,the pathological complete response (pCR)rate in the NAIC group (13 patients,25%)was significantly higher than that in the NAC group (2 patients,3.8%,P<0.05 ).Similar results were observed in terms of major pathological response (MPR),with 23 patients (43%)in the NAIC group achieving MPR,while 9 patients (17%)in the NAC group achieved MPR (P<0.05 ).In terms of safety,the incidence of treatment-related adverse events (TRAEs) of any grade in the NAIC group and the NAC group was comparable (96.2% and 96.2%,respectively).In an exploratory subgroup analysis of tumor pathological regression,the patients with clinicopathological features such as age<65 years,male,stage Ⅲ~Ⅳ A of American Joint Committee on Cancer (AJCC)staging,histological type of adenocarcinoma,high-moderate differentiated,intestinal-type gastric cancer,stage T3~4 of clinical T-staging,and stage N2~3 of clinical N-staging were more likely to benefit from NAIC.Conclusion NAIC results in a higher rate of pathological regression and a comparable incidence of adverse events when compared with chemotherapy alone for patients with local advanced gastric adenocarcinoma.
3.Predictive analysis and risk assessment of Kümmell's disease in patients with osteoporotic vertebral compression fractures
Zengjing LIU ; Linghong WU ; Jiarui CHEN ; Mingbo WANG ; Xianglong ZHUO ; Xiaozhong PENG ; Xiangtao XIE
Chinese Journal of Orthopaedics 2024;44(11):756-763
Objective:To analyze predictive risk indicators associated with the development of Kümmell's disease (KD) in patients with osteoporotic vertebral compression fractures (OVCFs).Methods:A 1∶1 frequency-matched case-control study design was employed, selecting patients who visited the Department of Spine Surgery at Liuzhou Workers' Hospital from January 2021 to June 2023. Patients were divided into case and control groups based on whether they progressed to Kümmell's disease (KD). Detailed demographic information, comorbidities, and laboratory data were collected, and baseline characteristics of the two groups were compared. Initial predictive variables significantly associated with the target variable were preliminarily screened through univariate analysis. A correlation heatmap was then constructed to assess collinearity among these variables, followed by further selection of potential predictors using the Lasso regression model. Finally, a multivariable logistic regression model was used for the prediction and analysis of KD-related risk indicators.Results:Univariate analysis identified significant predictors of Kümmell's disease, including patient age, bone mineral density, kyphotic Cobb angle, and multiple vertebral fractures. These were included in the subsequent Lasso regression analysis, which identified key predictors with non-zero coefficients: age, bone density, Cobb angle, multiple vertebral fractures, platelet count (PLT), aspartate aminotransferase/alanine aminotransferase (AST/ALT), albumin (Alb), albumin/globulin ratio (Alb/Glb), alkaline phosphatase (ALP), urea (UREA), serum uric acid (SUA), fibrinogen (Fn), blood glucose (BG), and C-reactive protein (CRP). The correlation heatmap revealed the correlation and collinearity risks between these variables, with ALT and AST/ALT showing a high correlation ( r=0.750) and PLT and Alb showing a low correlation ( r=-0.110). Multivariable logistic regression indicated that the presence of multiple vertebral fractures [ OR=2.078, 95% CI (1.072, 4.025), P=0.030], increased Cobb angle [ OR=1.033, 95% CI (1.008, 1.058), P=0.009], elevated levels of ALP [ OR=1.013, 95% CI(1.004, 1.023), P=0.006], and SUA [ OR=1.004, 95% CI (1.000, 1.007), P=0.043] were associated with an increased risk of KD in patients with OVCFs. Conversely, decreased levels of Fn [ OR=0.996, 95% CI (0.992, 0.999), P=0.008] were linked to an increased risk of KD. Conclusion:Multiple vertebral fractures, increased Cobb angle, elevated levels of ALP and SUA, along with decreased levels of Fn, can be used as early-warning indicators to predict whether patients with OVCFs will develop KD. Monitoring these indicators is crucial for the early detection and intervention in these patients.
4.Intelligent transportation service based on the " Didi" mode in a certain hospital
Kun CAO ; Shuangning CAI ; Minxi ZHENG ; Linghong MAO ; Fei WANG ; Jiya CHEN
Chinese Journal of Hospital Administration 2024;40(6):464-467
Transportation service is an important part of hospital logistics management. In 2023, a tertiary hospital centered on patient service and guided by lean management, launched an intelligent transportation service in the " Didi" mode on the basis of the medical internet of things platform. This practice investigated the status of hospital transportation services and developed an intelligent transportation system that includes three subsystems: task reception and generation, dispatch and command of transportation center, and handheld computer accepting order. At the same time, standardized business processes were developed and transportation service performance evaluations were implemented. This practice had gradually piloted and achieved intelligent management of hospital transportation services. As of December 2023, the hospital had completed a total of about 310 thousand transportation tasks, of which 70% were intelligent system dispatching tasks. The timely delivery service rate had increased from 58% in 2022 to 98% in 2023. This practice had improved the quality and efficiency of transportation services, promoted the high-quality development of hospital logistics management, which could provide references for other hospitals to improve logistics management efficiency.
5.Clinical characteristics of cryptococcal meningitis patients with anti-granulocyte-macrophage colony-stimulating factor autoantibodies
Yu LUO ; Rongsheng ZHU ; Jiahui CHENG ; Linghong ZHOU ; Wenjia QIU ; Juntian HUANG ; Yingkui JIANG ; Xuan WANG ; Huazhen ZHAO ; Liping ZHU
Chinese Journal of Infectious Diseases 2023;41(8):495-501
Objective:To investigate the clinical characteristics and prognosis of cryptococcal meningitis patients with anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies.Methods:A total of 216 non-acquired immunodeficiency syndrome (AIDS) related cryptococcal meningitis cases with positive cultures of Cryptococcus, hospitalized at Huashan Hospital, Fudan University during January 2014 and December 2021, were retrospectively included. The serum anti-GM-CSF autoantibodies were detected by enzyme linked immunosorbent assay, and the clinical characteristics and prognosis were compared between patients with and without anti-GM-CSF autoantibodies. Statistical comparisons were mainly performed using the chi-square test or Fisher′s exact test. Cox proportional-hazards model was used to analyze the risk factors associated with prognosis. Results:Among 216 enrolled patients, 23 patients were positive of anti-GM-CSF autoantibodies, with a positive rate of 10.6%. Among 23 patients, seven cases were infected with Cryptococcus gattii, and 16 cases were infected with Cryptococcus neoformans. In the group with positive anti-GM-CSF autoantibodies, 30.4%(7/23) of the patients were infected with Cryptococcus gattii, which was higher than that of 1.6%(3/193) in the group with negative anti-GM-CSF autoantibodies, and the difference was statistically significant ( χ2=38.82, P<0.001). In the group with positive anti-GM-CSF autoantibodies, 30.0% (6/20) had mass lesions with a diameter greater than three centimeters in the lungs, and the one-year all-cause mortality rate was 50.0% (10/20), which were both higher than those of 3.4%(5/145) and 16.1% (29/180) in the negative group, respectively. The differences were both statistically significant (both Fisher′s exact test, P<0.01). Age≥60 years (hazard ratio ( HR)=4.146, P=0.002), predisposing factors ( HR=3.160, P=0.021), epilepsy ( HR=6.129, P=0.002), positive anti-GM-CSF autoantibodies ( HR=2.675, P=0.034), white blood cell count of cerebrospinal fluid (CSF)<100 ×10 6/L ( HR=2.736, P=0.039), the titers of cryptococcal capsular polysaccharide antigen of CSF≥1∶1 280 ( HR=4.361, P=0.009) were independent risk factors for one-year all-cause mortality in patients with cryptococcal meningitis. Conclusions:In non-AIDS related cryptococcal meningitis patients, the positive rate of serum anti-GM-CSF autoantibodies is as high as 10.6%. Patients with anti-GM-CSF autoantibodies could be infected with both Cryptococcus neoformans and Cryptococcus gattii, and they have higher proportion of lung mass lesions than patients with negative anti-GM-CSF autoantibodies. The one-year survival rate decreases significantly in patients with anti-GM-CSF autoantibodies, which is an independent risk factor for the prognosis of cryptococcal meningitis.
6.Efficacy and safety of high-dose caspofungin in the treatment of invasive pulmonary aspergillosis
Linghong ZHOU ; Xuan WANG ; Ruiying WANG ; Huazhen ZHAO ; Yingkui JIANG ; Jiahui CHENG ; Jingyun YE ; Liping HUANG ; Liping ZHU
Chinese Journal of Infectious Diseases 2019;37(3):139-143
Objective To investigate the clinical efficacy and safety of high-dose caspofungin (70 mg/d)as initial or salvage treatment for invasive pulmonary aspergillosis.Methods Twenty-one patients with proven or probable invasive pulmonary aspergillosis from June 2014 to October 2017 in Huashan Hospital,Fudan University were retrospectively reviewed.According to the anti-fungal treatment before high-dose caspofungin application,patients were divided into initial treatment group and salvage treatment group.Patients' clinical data and laboratory data were collected.The characteristics,clinical efficacy,adverse reactions,one-year survival rate and the overall effective rate were evaluated.The prognosis of the two groups was compared by Kaplan-Meier analysis.Results Twenty of the 21 patients opportunistic acquired invasive pulmonary aspergillosis during the treatment of underlying diseases.Five patients were initially treated with high-dose caspofungin for 68 (62) days.At week 12,one patient achieved complete response,3 patients achieved partial response,and the overall effective rate was 80% (4/5).Sixteen patients received caspofungin as salvage therapy for 66.50 (58) days,of which one patient got complete response at week 12,10 had partial response,and the overall effective rate was 68.75% (11/16).One-year follow-up showed that no patient died in the initial treatment group,and the one-year survival rate was 100% (5/5).In salvage treatment group,3 patients died of pulmonary bacterial infections and the one-year survival rate was 81.25% (13/16).During treatment,one patient had elevated total bilirubin,which was possibly associated with high-dose caspofungin.Conclusions High-dose caspofungin regimen has good efficacy and safety,both for initial treatment and salvage therapy in patients with invasive pulmonary aspergillosis.
7.Rrelationship between liver volume atrophy rate,liver stiffness measurements and Child-Turcotte-Pugh value with Laennec histopathological classification in patients with hepatitis B cirrhosis
Qincheng LIU ; Ning LIU ; Xiaoyu HAN ; Linghong GUO ; Chunming WANG ; Caixian LIAO
Chongqing Medicine 2018;47(14):1870-1873,1877
Objective To explore the relationship between the liver volume atrophy rate,liver stiffness measurements(LSM) and Child-Turcotte-Pugh(CTP) value with the Laennec histopathological classification in the patients with hepatitis B cirrhosis and its value in the quantitative diagnosis of liver cirrhosis degree.Methods The clinicopathological data of liver biopsy tissue pathological slides,FibroScan,CT examination and hematological detection in 32 cases of hepatitis B cirrhosis were retrospectively analyzed.Liver cirrhosis was divided into mild,moderate and severe according to the Laennec liver cirrhosis histopathological classification.Then the relationship between the liver volume atrophy rate,LSM and CTP score with liver cirrhosis histopathological.Results Among 32 cases,9 cases(28.12%) were mild,12 cases(37.50%) were moderate and 11 cases(34.38%) were severe.The liver volume atrophy rates of mild,moderate and severe groups were (16.75±2.20)%,(23.11±6.67)% and(35.55±5.70)% respectively;LSM were(14.96±3.36),(20.21± 3.07),(37.03 ± 16.44) kPa respectively,the difference among 3 groups was statistically significant (P< 0.01).The CTP scores had no statistical difference among the 3 groups were(P>0.05).The cirrhosis histopathological grade had the positive correlation with the liver volume atrophy rate and LSM(r=0.93,0.74,P<0.01),however had no obvious correlation with the CTP scores(r=0.27,P>0.05);the liver volume atrophy rate was positively correlated with LSM and CTP score(r=0.90,0.91,P<0.01);while LSM had no obvious correlation with CTP score (r =0.15,P > 0.05).Conclusion The more severe the cirrhosis histoathological grade,the bigger the liver volume atrophy rate and the higher the FibroScan detection value;the liver volume atrophy rate and LSM may serve as the quantitative diagnosis indicators of liver fibrosis histopathological severity.
8.Investigation on the Ethical Cognition of Clinical Research among Medical Staff in Hospitals of Qinghai Province
Linghong ZHU ; Xiumin HAN ; Jingni ZHANG ; Pei HNA ; Li JI ; Bo WANG ; Qiang ZHANG
Chinese Medical Ethics 2017;30(6):753-756
Objective:To investigate the ethical cognition of clinical research among medical staff working at different grades of hospitals in Qinghai Province and thus to provide references for the construction of medical ethics organization in hospitals.Methods:A questionnaire survey was conducted to investigate the knowledge of hospital ethics among medical staff from 11 hospitals of different grades in Qinghai Province.Results:Among the 611 med-ical staff,329 (53.8%) received medical ethics education in continuing education and 378 (61.9%) knew that the ethics committee had been set up in their hospitals.The medical staff in different grades of hospitals showed a statistical difference (P < 0.05) in the medical behavior cognition of ethical laws and regulations and the need for ethical review.Conclusion:Hospitals in Qinghai province need to strengthen the training of medical ethics knowl-edge,improve medical staff's awareness of ethics committee,and promote the efficient operation of hospital ethics.
9.A retrospective review of 46 cases of chronic invasive fungal rhinosinusitis
Huimin XU ; Linghong ZHOU ; Qian LI ; Yuekai HU ; Haoxiang ZHU ; Yanli QIN ; Zhongqing CHEN ; Xuan WANG ; Liping ZHU
Chinese Journal of Infectious Diseases 2017;35(9):537-540
Objective To investigate the clinical characteristics of chronic invasive fungal rhinosinusitis.Methods Clinical features and outcomes of 46 proven cases of chronic invasive fungal rhinosinusitis admitted in Huashan Hospital,Fudan University from January 2009 to December 2016 were retrospectively reviewed.Results Of the 46 patients enrolled,left sphenoid sinus,ethmoid sinus and maxillary sinus were affected in 24,23 and 20 cases,respectively,while right maxillary sinus,ethmoid sinus and sphenoid sinus were affected in 18,16 and 15 eases,respectively.Left and right frontal sinus were affected in 9 and 6 cases,respectively.The central nervous system and orbit were the most commonly affected sites in external nasal involvements,noted in 22 cases respectively.Left sphenoid (17 cases) and ethmoid sinus (15 cases) involvements were most common in central nervous system affected patients.Left sphenoid (14 cases) and ethmoid sinus (13 cases) involvements were most common in orbit affected patients.Aspergillus species were the primary pathogens observed in 42 eases.Zygomycete,candida and dark filamentous fungus were observed in two,one and one case,respectively.Pathologically,37 of the cases were chronic nongranulomatous type and the left 9 were chronic granulomatous type who were all immunocompetent hosts.The initial symptoms usually included headache,dizziness and nasal discomforts including nasal obstruction and purulent secretion.The chief complaints usually included headache,dizziness,and visual disturbances including blurred vision,vision loss or even blindness.Antifungal treatment combined with surgical interventions for removal or drainage focus lesions achieved significant effect,and 42 patients were cured.Conclusions Chronic invasive fungal rhinosinusitis should be taken into consideration in the presence of nasal discomforts or nonspecific symptoms such as headache and dizziness.The possibility of chronic invasive fungal rhinosinusitis should be cautious after the emergence of vision abnormalities.
10.Analysis of the clinical effect of methylprednisolone in the treatment of patients with acute myelitis
Linghong WANG ; Juxiu HUANG ; Yuping LI ; Litong JIN
Chinese Journal of Primary Medicine and Pharmacy 2016;23(3):397-399
Objective To study the clinical curative effect and complication of methylprednisolone in the treatment of patients with acute myelitis.Methods 42 patients with acute myelitis were selected and randomly divid-ed into two groups,21 cases in each group.The control group was treated with dexamethasone,the observation group was treated with methylprednisolone.After treatment,the clinical parameters and effect of the two groups were com-pared.Results The total effective rate of the observation group was 85.7%,which was higher than 42.9% of the control group (χ2 =2.41,P <0.05).The improvement of muscle strength,restore micturition,walk on their own time in the observation group were (10.1 ±4.1)d,(7.1 ±3.4)d,(16.1 ±4.2)d,respectively,which were better than (23.4 ±7.3)d,(10.2 ±3.1)d,(22.6 ±7.3)d in the control group(t =3.15,1.69,1.97,all P <0.05).The total incidence of gastrointestinal reaction and complication rates of the observation group was 4.8%,which was lower than 19.0% of the control group (χ2 =6.37,P <0.05).Conclusion In treatment of patients with acute myelitis,methyl-prednisolone has good effect,which should be used in clinical practice.

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