OBJECTIVE: To explore the clinical significance of circulating tumor DNA (ctDNA) in response evaluation and relapse monitoring for patients with primary mediastinal large B-cell lymphoma (PMBCL). METHODS: The clinical characteristics, efficacy and survival of 38 PMBCL patients in our hospital from January 2010 to April 2020 were retrospectively analyzed. The ctDNA monitoring was conducted by targeted next-generation sequencing (NGS). RESULTS: Among the 38 patients, 26 cases were female, and 32 cases were diagnosed with Ann Arbor stage I-II. The 5-year overall survival (OS) rate and progression-free survival (PFS) rate were 74.7% and 61.7%, respectively. Males and those with high aaIPI scores (3 points) had a relatively poor prognosis. The NGS results of 23 patients showed that STAT6 (65.2%), SOCS1 (56.5%), and TNFAIP3 (56.5%) were the most common mutated genes. Patients with stable disease (SD)/progressive disease (PD) exhibited enrichment in cell cycle, FoxO, and TNF signaling pathways. A total of 29 patients underwent end-of-treatment PET/CT (EOT PET/CT), and 16 of them received ctDNA monitoring with 12 negative. Among 6 patients with EOT PET/CT positive (Deauville 4), 4 underwent ctDNA monitoring, and 3 of them were negative, being still in continuous remission without any subsequent anti-tumor therapy. CONCLUSION CtDNA may be combined with PET/CT to assess efficacy, monitor relapse, and guide treatment of PMBCL.
Humans ; Circulating Tumor DNA/blood* ; Female ; Mediastinal Neoplasms ; Male ; Retrospective Studies ; High-Throughput Nucleotide Sequencing ; Prognosis ; Lymphoma, Large B-Cell, Diffuse/genetics* ; Middle Aged ; Adult ; Aged ; Neoplasm Recurrence, Local ; Mutation

As the base of the three-tier rural health service network,primary health-care institutions are facing major bottlenecks,such as mismatches with residents'health service needs,shrinking capacity and serious patient losses.The formation of supply and demand service'stickiness'is a key path to promote patient primary care,maintain the sustainable development of the primary health service system,and improve the health of rural residents from a micro perspective,and it is also an important means to address the many challenges of the development of rural primary health care in the new era.Through the case study of X Township Health Center in Qianjiang District,Chongqing,this study found that the health centre was once caught in the difficulties of patient outflow,backward assessment and development restrictions,but in recent years,the institution has turned passivity into initiative,and gradually formed the service'stickiness'between supply and demand by optimizing the service contact process and improving the perceived quality of the residents.The formation of supply and demand'stickiness'is not only conducive to the retention of patients and the enhancement of health management,but also increases the income of primary health care institutions and promotes their sustainable development,which provides valuable practical experience for the transformation and development of primary health care.

As the base of the three-tier rural health service network,primary health-care institutions are facing major bottlenecks,such as mismatches with residents'health service needs,shrinking capacity and serious patient losses.The formation of supply and demand service'stickiness'is a key path to promote patient primary care,maintain the sustainable development of the primary health service system,and improve the health of rural residents from a micro perspective,and it is also an important means to address the many challenges of the development of rural primary health care in the new era.Through the case study of X Township Health Center in Qianjiang District,Chongqing,this study found that the health centre was once caught in the difficulties of patient outflow,backward assessment and development restrictions,but in recent years,the institution has turned passivity into initiative,and gradually formed the service'stickiness'between supply and demand by optimizing the service contact process and improving the perceived quality of the residents.The formation of supply and demand'stickiness'is not only conducive to the retention of patients and the enhancement of health management,but also increases the income of primary health care institutions and promotes their sustainable development,which provides valuable practical experience for the transformation and development of primary health care.

A liquid chromatography-tandem mass spectrometry method was established and validated for determining the concentrations of costunolide(CO), piperine(PI), agarotetrol(AG), glycyrrhizic acid(GL), vanillic acid(VA), and glycyrrhetinic acid(GA) in rat plasma. This method was then applied to the toxicokinetic study of these six compounds in rats with chronic cerebral ischemia(CCI) following multiple oral doses of Zhachong Shisanwei Pills. Finally, the effects of continuous multiple-dose administration of Zhachong Shisanwei Pills on the liver of CCI rats were investigated. The results showed that after oral administration of different doses of Zhachong Shisanwei Pills, the in vivo exposure of AG, VA, and GA was relatively high, with AUC_(0-∞) values ranging from 604.0-2 494.2, 1 305.4-4 634.5, and 2 177.5-4 045.7 h·ng·mL~(-1), respectively, while the exposure of CO, PI, and GL was relatively low, with AUC_(0-∞) values ranging from 37.8-238.2, 2.4-17.0, and 146.9-408.5 h·ng·mL~(-1), respectively. The C_(max) and AUC_(0-∞) of the six compounds were positively correlated with the administered dose. The T_(max) of PI and AG ranged from 0.3 to 2.0 h, their T_(1/2) ranged from 0.8 to 2.9 h, and their mean residence time(MRT) ranged from 1.0 to 3.7 h. The T_(max) of GL and VA was shorter(0.4-1.9 h), while their T_(1/2)(2.6-5.9 h) and MRT(2.5-8.5 h) were longer. Both CO and GA exhibited a bimodal phenomenon, with T_(max) ranging from 1.6 to 6.6 h, T_(1/2) ranging from 2.8 to 7.7 h, and MRT ranging from 4.1 to 12.9 h. Liver histopathology after 28 days of continuous multiple-dose administration of Zhachong Shisanwei Pills showed that the liver tissue remained normal at a low dose(crude drug 0.8 g·kg~(-1), approximately 5 times the clinical equivalent dose). However, as the dose increased(crude drug 1.1-3.0 g·kg~(-1), 6.9-18.8 times the clinical equivalent dose), varying degrees of liver damage were observed. Blood biochemical tests revealed no significant changes in the serum levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), alkaline phosphatase(ALP), and total bile acid(TBA) in CCI rats from administration groups 1 to 3(crude drug 0.8, 1.1, 1.5 g·kg~(-1)). However, ALT, AST, ALP, and TBA levels in groups 4 and 5(crude drug 2.1, 3.0 g·kg~(-1)) showed significant increases. This study preliminarily elucidated the toxicokinetic characteristics of the six compounds in Zhachong Shisanwei Pills and their effects on liver tissue in CCI rats, providing data as a reference for clinical use.
Animals ; Tandem Mass Spectrometry/methods* ; Rats ; Drugs, Chinese Herbal/toxicity* ; Male ; Rats, Sprague-Dawley ; Brain Ischemia/blood* ; Chromatography, Liquid/methods* ; Polyunsaturated Alkamides/blood* ; Piperidines/toxicity* ; Benzodioxoles/toxicity* ; Alkaloids/blood* ; Liquid Chromatography-Mass Spectrometry

Objective:To explore the therapeutic efficacy and prognostic factors of induction therapy for secondary central nervous system lymphoma(SCNSL).Methods:Clinical data of patients diagnosed with SCNSL from 2010 to 2021 at Guangdong Provincial People's Hospital were retrospectively collected.A retrospective cohort study was performed on all and grouped patients to analyze the efficacy and survival.Multivariate logistic regression analysis was used to explore the adverse prognostic factors.Results:Thirty-seven diffuse large B-cell lymphoma patients with secondary central involvement were included in the research.Their 2-year overall survival(OS)rate was 46.01％and median survival time was 18.1 months.The 2-year OS rates of HD-MTX group and TMZ group were 34.3％and 61％,median survival time were 8.7 and 38.3 months,and median progression-free survival time were 8.1 and 47 months,respectively.Multivariate logistic regression analysis showed that age,sex,IPI,Ann Arbor stage were correlated with patient survival time.The median survival time of patients with CD79B,KMT2D,CXCR4.ERBB2,TBL1XR1,BTG2,MYC,MYD88,and PIM1 mutations was 8.2 months,which was lower than the overall level.Conclusion:HD-MTX combined with TMZ as the first-line strategy may improve patient prognosis,and early application of gene sequencing is beneficial for evaluating prognosis.

This paper evaluates the impact of basic medical insurance on the health status of flexible employees based on the CFPS three-period balanced panel data from 2016 to 2020,using Ordered Probit Model and Two-way Fixed Effects Model.It is found that basic medical insurance significantly promotes the physical and mental health of flexible employees.Further heterogeneity analysis reveals that the health performance of basic medical insurance was particularly significant for middle-aged and old-aged,rural,east-central and better-educated flexible employees.In addition,the mediation effect analysis indicates that basic medical insurance promots the health of flexible employees through the mediation channels of improving the utilization of medical services and reducing the burden of disease costs.This paper suggests promoting the comprehensive participation of flexible employees;improving the medical insurance system for middle-aged and elderly flexible employees;accelerating the sinking of high-quality medical resources to rural and western areas;and actively exploring a new mode of participation in medical check-ups by flexible employees,with a view to lowering the incidence of serious illnesses and major illnesses among flexible employees and improving health performance.

Objective To explore the effect and prognostic factors of intravenous thrombolysis combined with Trevo stent mechanical thrombectomy in the treatment of ischemic stroke.Methods A total of 120 patients with ischemic stroke diagnosed and treated in our hospital from January 2020 to December 2022 were selected as research objects and divided into two groups according to random number table method,with 60 cases in each group.Both groups were given basic treatment,the control group was given intravenous thrombolytic therapy,and the observation group was given intravenous thrombolytic therapy combined with mechanical thrombectomy with Trevo stent.The clinical efficacy of the two groups was observed,and the patients were divided into a good prognosis group(46 cases)and a poor prognosis group(74 cases)according to the prognosis.Clinical data such as gender,age,BMI,combined hypertension,combined diabetes,smoking,treatment methods,complete vascular recirculation rate,preoperative NIHSS score and postoperative NIHSS score of the two groups were collected.The independent prognostic factors were analyzed by univariate and multivariate binary Logistic regression.Results The total effective rate of the study group was significantly higher 88.33％(53/60)than that of the control group 73.33％(44/60),and the difference was statistically significant(P＜0.05).Univariate analysis showed that there were no statistically significant differences in gender,BMI,diabetes mellitus,and preoperative NIHSS score between the two groups(P＞0.05),while there were statistically significant differences in age,hypertension,smoking,treatment style,complete vascular revasculosity,and postoperative NIHSS score between the two groups(P＜0.05).Logistic regression analysis showed that age,treatment style and complete vascular revasculopathy rate were independent factors affecting the prognosis of ischemic stroke patients(P＜0.05).Conclusion Intravenous thrombolysis combined with mechanical thrombectomy with Trevo stent can improve the clinical efficacy and prognostic quality of ischemic stroke patients in the time window of intravenous thrombolysis.In addition,the prognosis of patients with ischemic stroke is also closely related to the age of patients and the rate of complete vascular recirculation after surgery.

Objective: To explore the prognostic factors of extracellular NK/T cell lymphoma (ENKTL) treated with pegaspargase/L-asparaginase. Methods: The clinical data of 656 ENKTL patients diagnosed at 11 medical centers in the Huaihai Lymphoma Working Group from March 2014 to April 2021 were retrospectively analyzed. The patients were randomly divided into two groups: a training set (460 cases) and a validation set (196 cases) at 7∶3, and the prognostic factors of the patients were analyzed. A prognostic scoring system was established, and the predictive performance of different models was compared. Results: Patients' median age was 46 (34, 57) years, with 456 males (69.5% ) and 561 nasal involvement (85.5% ). 203 patients (30.9% ) received a chemotherapy regimen based on L-asparaginase combined with anthracyclines, and the 5-year overall survival rate of patients treated with P-GEMOX regimen (pegaspargase+gemcitabine+oxaliplatin) was better than those treated with SMILE regimen (methotrexate+dexamethasone+cyclophosphamide+L-asparaginase+etoposide) (85.9% vs 63.8% ; P=0.004). The results of multivariate analysis showed that gender, CA stage, the Eastern Cooperative Oncology Group performance status (ECOG PS) score, HGB, and EB virus DNA were independent influencing factors for the prognosis of ENKTL patients (P<0.05). In this study, the predictive performance of the prognostic factors is superior to the international prognostic index, Korean prognostic index, and prognostic index of natural killer lymphoma. Conclusion: Gender, CA stage, ECOG PS score, HGB, and EB virus DNA are prognostic factors for ENKTL patients treated with pegaspargase/L-asparaginase.
Male ; Humans ; Middle Aged ; Asparaginase/therapeutic use* ; Prognosis ; Retrospective Studies ; Lymphoma, Extranodal NK-T-Cell/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Etoposide ; Cyclophosphamide ; Methotrexate/therapeutic use* ; DNA/therapeutic use* ; Treatment Outcome

Objective: To assess the feasibility of nuclear score combined with cyclin D1 immunocytochemistry in classifying indeterminate thyroid nodules with fine-needle aspiration (FNA) cytological diagnosis of Bethesda category Ⅲ-Ⅴ. Methods: A consecutive cohort of 118 thyroid FNA specimens with indeterminate diagnosis (TBSRTC category Ⅲ-Ⅴ) and available histopathologic follow-up data were collected between December 2018 and April 2022 at the Department of Pathology, Beijing Hospital, China. These cases were subjected to cytological evaluation and cyclin D1 immunocytochemistry. The optimal cut-off points of a simplified nuclear score and the percentage of cyclin D1-positive cells for the diagnosis of malignancy or low-risk neoplasm were determined using the receiver operating characteristic (ROC) curves and area under the ROC curve (AUC). The specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) of nuclear score and cyclin D1 immunostaining were evaluated from the crosstabs based on cut-off points. The diagnostic accuracy of simplified nuclear score combined with cyclin D1 immunostaining was estimated using ROC curve analysis. Results: Nuclear grooves, intra-nuclear inclusions and chromatin clearing were more commonly found in malignancy/low-risk neoplasms than benign lesions (P=0.001, P=0.012 and P=0.001 respectively). A cut-off point of≥2 for the simplified nuclear score was sensitive for defining malignancy/low-risk neoplasm, and its PPV, NPV, sensitivity and specificity were 93.6%, 87.5%, 99.0% and 50.0% respectively. A positive cut-off point of 10% positive thyroid cells in cyclin D1 immunostaining demonstrated sensitivity of 88.5%, specificity of 100%, PPV of 100% and NPV of 53.8% for correctly detecting thyroid malignancy or low-risk neoplasm. The sensitivity and PPV of simplified nuclear score combined with cyclin D1 immunostaining were 93.3% and 100%, respectively. Both specificity and NPV were maintained at high levels (100% and 66.7%, respectively). The diagnostic accuracy of simplified nuclear score combined with cyclin D1 immunostaining in detecting thyroid malignancy/low-risk neoplasm was increased to 94.1% compared to using either of them alone. Conclusions: Combing simplified nuclear score and cyclin D1 immunostaining on FNA cytology specimens can increase the diagnostic accuracy in classifying thyroid nodules of indeterminate cytological categories. Thus, this supplementary approach provides a simple, accurate, and convenient diagnostic method for cytopathologists so that may reduce unnecessary thyroidectomies.
Humans ; Thyroid Nodule/pathology* ; Biopsy, Fine-Needle ; Cyclin D1 ; Immunohistochemistry ; Thyroid Neoplasms/pathology* ; Retrospective Studies

Objective:To establish a risk prediction model for neonatal asphyxia in cesarean section and test its application effect.Methods:This was a retrospective study. We retrospectively analyzed the clinical data of 2 244 infants (modeling group) who were delivered by cesarean section in Affiliated Hospital of Weifang Medical University from April 2021 to December 2021. Newborns were divided into asphyxia group ( n=176) and non-asphyxia group ( n=2 068) according to the occurrence of neonatal asphyxia. Logistic regression was used to screen the risk factors of neonatal asphyxia in cesarean section and a line chart model was established to predict the risk. Another 683 neonates were selected as validation group for external validation of the model from January to March in 2022. Results:Five factors including preterm birth, fetal distress, fetal growth restriction, abnormal S/D value of umbilical artery and umbilical cord around the neck were included in the prediction model. The area under ROC curve of the modeling group was 0.902, the Youden index was 0.687, the sensitivity was 0.837, and the specificity was 0.850. Hosmer-lemeshow test showed that χ2=1.79, and P=0.877. In the validation group, the area under ROC curve was 0.823, the Youden index was 0.555, the sensitivity was 0.835, and the specificity was 0.720. It showed that the model had a good fitting effect and identification validity. Conclusions:The risk prediction model has a good clinical application value in the prediction of neonatal asphyxia in cesarean section, and provides reference for obstetricians to take preventive management measures of neonatal asphyxia in time.