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Background: Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) is a life-threatening fungal infection. Studies focusing on CAPA in low- and middle-income countries are limited. Methods: This retrospective matched case-control study was conducted at a tertiary care center in South India. Cases of CAPA were classified using the 2020 European Confederation of Medical Mycology/International Society for Human and Animal Mycology consensus criteria. A total of 95 cases were matched 1:1 with COVID-19 patients without CAPA. Matching was done based on age and period of admission. Inverse probability weighting was used to account for imbalances in COVID-19 severity and intensive care unit (ICU) admission. Data on demographics, clinical details, microbiologic and radiologic data, and treatment outcomes were collected. A predictive score for CAPA was developed from baseline risk factors. Results: The predictive score identified lymphopenia, European Organisation for Research and Treatment of Cancer risk factors, and broad-spectrum antibiotic use as the main risk factors for CAPA. Positivity for bacterial pathogens in blood or bronchoalveolar lavage samples reduced the risk of CAPA. The predictive model performed well in cross-validation, with an area under the curve value of 82%. CAPA diagnosis significantly increased mortality and shift to ICU. Conclusions: The predictive model derived from the current study offers a valuable tool for clinicians, especially in high-endemic low- and middle-income countries, for the early identification and treatment of CAPA. With further validation, this risk score could improve patient outcomes.
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BACKGROUND: In recent years, there has been an increasing prevalence of patients with papillary thyroid microcarcinoma (PTMC) without lymph node involvement in medical centers worldwide. For patients who are unable to undergo active surveillance (AS) and are afraid of postoperative complications, conformal thyroidectomy may be a suitable option to ensure both preservation of function and complete removal of the tumor. METHODS: The patients in the cohort during 2010 to 2015 were retrospectively enrolled strictly following the inclusion and exclusion criteria. The observation and control groups were defined based on the surgical approach, with patients in the observation group undergoing conformal thyroidectomy and patients in the control group undergoing lobectomy. Event-free survival (EFS), the interval from initial surgery to the detection of recurrent or metastatic disease, was defined as the primary observation endpoint. RESULTS: A total of 319 patients were included in the study, with 124 patients undergoing conformal thyroidectomy and 195 patients undergoing lobectomy. When compared to lobectomy, conformal thyroidectomy demonstrated reduced hospital stays, shorter operative times, and lower rates of vocal cord paralysis and hypoparathyroidism. Furthermore, the mean bleeding volume during the operation and the rate of permanent hypothyroidism were also lower in the conformal thyroidectomy group than in the lobectomy group. However, there was no statistically significant difference observed in the 5- and 10-year EFS between the two groups. CONCLUSIONS: Conformal thyroidectomy had advantages in perioperative management and short-term complication rates, with an EFS that was not inferior to that of lobectomy. Thus, conformal thyroidectomy is a feasible option for low-risk PTMC patients.
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Carcinoma, Papillary , Thyroid Neoplasms , Thyroidectomy , Humans , Thyroidectomy/methods , Thyroidectomy/adverse effects , Female , Male , Thyroid Neoplasms/surgery , Thyroid Neoplasms/pathology , Thyroid Neoplasms/mortality , Retrospective Studies , Middle Aged , Carcinoma, Papillary/surgery , Carcinoma, Papillary/pathology , Carcinoma, Papillary/mortality , Adult , Follow-Up Studies , Feasibility Studies , Cohort Studies , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Treatment Outcome , Operative TimeABSTRACT
We measured the levels of High-Mobility Group Box 1 (HMGB1), Receptor for Advanced Glycation Endproducts (RAGE), T Helper 17 cells (Th17), Regulatory T cells (Treg), and related cytokines in the peripheral blood of patients with severe preeclampsia (SPE) complicated with acute heart failure (AHF) to explore the expression changes in these indicators. In total, 96 patients with SPE admitted to Gansu Provincial Maternity and Child-care Hospital between June 2020 and June 2022 were included in the study. The patients were divided into SPE+AHF (40 patients) and SPE (56 patients) groups based on whether they suffered from AHF. Additionally, 56 healthy pregnant women who either received prenatal examinations or were admitted to our hospital for delivery during the same period were selected as the healthy control group. An enzyme-linked immunosorbent assay was performed to detect the expression levels of HMGB1, RAGE, interleukin (IL)-17, IL-6, transforming growth factor ß (TGF-ß), IL-10, and NT-proBNP in plasma. Flow cytometry was employed to determine the percentages of Th17 and Treg cells. Compared to the healthy control group, the SPE+AHF and SPE groups had higher plasma levels of HMGB1 and RAGE expression, higher Th17 percentage and Th17/Treg ratio, and lower Treg percentage. Compared to the SPE group, the SPE+AHF group had higher plasma levels of HMGB1 and RAGE expression, higher Th17 percentage and Th17/Treg ratio, and lower Treg percentage (P < .05). In patients with SPE with AHF, plasma HMGB1 was positively correlated with RAGE, Th17, Th17/Treg, IL-17, and IL-6 and was negatively correlated with TGF-ß and IL-10 (P < .05). Our findings revealed that patients with SPE with AHF had elevated levels of HMGB1 and RAGE while exhibiting Th17/Treg immune imbalance, suggesting that the abnormal expression of these indicators may be involved in the pathogenesis of SPE with AHF.
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HMGB1 Protein , Pre-Eclampsia , Female , Humans , Pregnancy , Cytokines , Glycation End Products, Advanced/metabolism , HMGB1 Protein/metabolism , Hypertension/metabolism , Interleukin-10/metabolism , Interleukin-6 , Pre-Eclampsia/metabolism , Receptor for Advanced Glycation End Products/metabolism , T-Lymphocytes, Regulatory/metabolism , Transforming Growth Factor beta/metabolismABSTRACT
This study reported on the intratumor genomic and immunological heterogeneity of different tumor lesions from a single patient with multiple primary colorectal cancer (MPCC). The goal of this study was to explore the molecular and microenvironment characteristics of tumor lesions from different primary sites in a patient with MPCC. A total of three tumor lesions located in the hepatic flexure of the transverse colon, sigmoid colon, and rectum were collected from a 72-year-old male patient with MPCC. All three tumor samples were examined by using whole-exome sequencing (WES) and single-cell RNA sequencing (scRNA-seq). The transcriptome data of The Cancer Genome Atlas (TCGA) colon cancer (COAD) dataset were explored to characterize the biological impacts of certain immune cells. Only three nonsynonymous mutations were shared by all of the tumor lesions, whereas a number of single nucleotide variant (SNV) and copy number variation (CNV) mutations were shared by tumor samples from the sigmoid colon and rectum. Transcriptomic analysis showed that tumor lesions derived from the transverse colon had decreased levels of RTK, ERK, and AKT pathway activity, thus suggesting lower oncogenic properties in the transverse lesion compared to the other two samples. Further immune landscape evaluation by using single-cell transcriptomic analysis displayed significant intratumor heterogeneity in MPCC. Specifically, more abundant mucosal-associated invariant T (MAIT) cell infiltration was found in transverse colon tumor lesions. Afterwards, we found that higher MAIT cell infiltration may correlate with a better prognosis of patients with colon cancer (immunohistochemical status was MSI-L/pMMR) by using a publicly available TCGA dataset.
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Colonic Neoplasms , Neoplasms, Multiple Primary , Male , Humans , Aged , Transcriptome , DNA Copy Number Variations , Gene Expression Profiling , Neoplasms, Multiple Primary/pathology , Genomics , Tumor Microenvironment/geneticsABSTRACT
Purpose To explore the diagnostic efficiency of ultrasound(US)combined with contrast-enhanced ultrasound(CEUS)in breast lesions and to analyze the related factors affecting the diagnostic accuracy.Materials and Methods From January 2022 to February 2023,the clinical data and ultrasound images of 784 patients who underwent breast US and CEUS examination with definite pathological results were retrospectively collected in the First Medical Center of the PLA General Hospital.The diagnostic efficacy of US combined with CEUS in benign and malignant breast lesions was analyzed,respectively.The independent risk factors for diagnostic errors were analyzed via Logistic regression.Results The sensitivity,specificity and accuracy of US combined with CEUS in the diagnosis of benign and malignant breast lesions were 89.2%,84.4%and 88.7%,respectively.The area under the receiver operating characteristic curve was 0.932.The results of multivariate Logistic regression analysis showed that the diagnosis error rate increased when the lesions were non-mass type(odds ratio,OR=1.927,P=0.047),complex cystic and solid(OR=3.729,P=0.000),and high-enhanced CEUS(OR=1.937,P=0.023),while the diagnosis error rate decreased when the lesions were large(OR=0.688,P=0.004)and with US-detect suspicious lymph node(OR=0.143,P=0.011).Conclusion When the breast lesions are non-mass type,complex cystic and solid lesions and hyper-enhancement,the diagnosis error rate of US combined with CEUS increased.It is necessary to further explore the enhancement patterns of different lesions.
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Purpose To explore the correlation between phosphatidylinositol 3 kinase/serine-threonine kinase(PI3K/AKT)signaling pathway and elastic characteristics of breast lesions.Materials and Methods A total of 115 breast lesions were prospectively analyzed in 114 patients who underwent surgery from May 2021 to May 2022 at Chinese PLA General Hospital.Ultrasound and shear wave elastography were performed preoperatively.Immunohistochemical staining was used to detect the expression of PI3K/AKT protein levels in the tissue specimens,and the correlation between the staining results and the elastic parameters of shear wave elastography was analyzed.Results Surgical pathology revealed benign breast lesions in 50 cases and malignant lesions in 65 cases(25 cases with axillary lymph node metastasis).The maximum modulus of elasticity(F=40.47),the average modulus of elasticity(F=45.11),the ratio of elasticity of the lesion to that of the surrounding tissue(F=48.98),the detection rate of"hard ring sign"(χ2=62.25),the expression level of PI3K/p-PI3K(F=15.19,58.95)and AKT/p-AKT(F=46.94,74.21)were found in benign and malignant lesions without axillary lymph node metastasis,malignant lesions with axillary lymph node metastasis(all P<0.05).The expression levels of PI3K/p-PI3K and AKT/p-AKT were positively correlated with the maximum elastic modulus value,the mean elastic modulus value,and the ratio of elasticity of the lesion to the surrounding tissues(r=0.475,0.475,0.451;r=0.533,0.540,0.542;r=0.371,0.402,0.445;r=0.482,0.455,0.545,all P<0.05).Conclusion The expression level of PI3K/AKT in breast lesions is correlated with elastic characteristics,suggesting that it plays an important role in the regulation of elastic characteristics of breast lesions.
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Objective To analyze the factors related to early allograft dysfunction(EAD)after liver transplantation and to construct a predictive model.Methods A total of 375 patients who underwent liver transplantation in our hospital from December 2008 to December 2021 were collected,including 90 patients with EAD and 266 patients without EAD.Thirty items of baseline data for the 2 groups were compared and analyzed.Aftergrouping in a ratio of 7∶3,univariate and multivariate logistic regression analyses were used in the training set to evaluate the factors related to EAD and construct a nomogram.Receiver operating characteristic(ROC)curve,decision curve analysis(DCA),sensitivity,specificity,positive predictive value,negative predictive value,Kappa value and other indicators were used to evaluate the model performance.Results The incidence of EAD after liver transplantation was 24%.Multivariate logistic regression analysis showed that preoperative tumor recurrence history(OR=3.15,95%CI:1.28~7.77,P=0.013)and operation time(OR=1.22,95%CI:1.04~1.42,P=0.015)were related to the occurrence of EAD after surgery.After predicting the outcome according to the cut-off point of 0.519 identified by the Youden index,the model performance in the both training set and validation set was acceptable.DCA suggested the model has good clinical applicability.Conclusion The risk factors for EAD after liver transplantation are preoperative tumor recurrence history and operation time,and the established model has predictive effect on prognosis.
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Objective To analyze the risk factors for severe illness caused by coronavirus disease 2019 in Fuzhou city.Methods The data of 4081 confirmed cases with current address in Fuzhou was collected from China Information System for Disease Control and Prevention from January 1 to June 30,2023.The epidemiological data of those cases was investigated such as the demographic characteristics,clinical manifestations and past medical history,etc.The risk factors of severe cases were analyzed by using the logistic regression.Results 4081 confirmed cases had been reported including 671 severe cases and 3410 non-severe cases.The demographic characteristics of severe cases,such as the proportion of male,age and current address in community were higher than that of non-severe cases,vaccination rate was lower than non-severe cases(59.02%vs.80.12%),the differences are statistically significant(P<0.001).The clinical manifestations such as interval time between onset and visit(P=0.001),fever(P=0.002),difficulty in breathing/shortness of breath(P=0.001)were the factors related to severe illness.The past medical histories such as history of chronic lung disease,history of heart cerebrovascular disease of severe cases,were higher than that of non-severe cases(P<0.001).Multivariate logistic regression showed that the male,the higher age,current address in community,no vaccination,the longer interval time between onset and visit,fever,difficulty in breathing/shortness of breath,the history of chronic lung disease,the history of heart cerebrovascular disease raised the risk of becoming severe cases.The healing time for severe cases was longer than that for non-severe cases(P<0.001).Conclusion Sex,age,current address,vaccination,interval time between onset and visit,fever,difficulty in breathing/shortness of breath,history of chronic lung disease,and history of heart cerebrovascular disease are the influencing factors for severe illness.
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Objective·To evaluate the relationship between body mass index(BMI)and chronic metabolic diseases.Methods·The elderly(≥60 years old)who were underwent physical examination in the Physical Examination Center of Renji Hospital,Shanghai Jiao Tong University School of Medicine from 2014 to 2021 were studied.Their results of biochemical indicators were collected.Their height,body weight,and blood pressure were measured by trained nurses.The history of chronic metabolic diseases was collected by self-reported questionnaire.Systolic blood pressure≥140 mmHg(1 mmHg=0.133 kPa),diastolic blood pressure≥90 mmHg,or self-reported hypertension history was defined as hypertension.Fasting blood glucose≥7.0 mmol/L or self-reported history of diabetes was defined as diabetes.Total cholesterol≥6.2 mmol/L,triglyceride≥2.3 mmol/L,or self-reported history of dyslipidemia was defined as dyslipidemia.The relationship between BMI and hypertension,diabetes,and dyslipidemia was evaluated by using receiver operator characteristic(ROC)curve analysis and binary logistic regression.Results·Data of 59 083 subjects were collected[30 807 men and 28 276 women,average age:(67.9±6.3)years old].The prevalence of hypertension,diabetes and dyslipidemia was 76.5%(45 219/59 083),24.1%(14 225/59 083)and 50.0%(29 544/59 083),respectively.Compared to the elderly people aged 60?74 years,those aged 75 years and above had a higher proportion of hypertension and diabetes,and a lower proportion of dyslipidemia and no metabolic abnormalities.With ROC analysis,the BMI cut-off values for hypertension,diabetes,and dyslipidemia were 24.3,23.9,and 23.9 kg/m2.The BMI cut-off values for hypertension and diabetes in elderly men were similar to those in elderly women(for hypertension:24.3 kg/m2 in elderly men vs 24.2 kg/m2 in elderly women;for diabetes:24.0 kg/m2 in elderly men vs 23.7 kg/m2 in elderly women);however,BMI cut-off value for dyslipidemia was obviously higher in elderly men than that in elderly women(24.0 kg/m2 in elderly men vs 22.5 kg/m2 in elderly women).The BMI cut-off value for chronic metabolic diseases was higher in the elderly people aged 60?74 years than that in the elderly people aged 75 years and above(24.2?24.7 kg/m2 vs 22.9?23.8 kg/m2).Conclusion·Elderly people aged 60?74 years should maintain the BMI below 24.0 kg/m2,while those aged 75 years and above should aim for the BMI below 23.0 kg/m2,so as to reduce the risk of chronic metabolic diseases.
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【Objective】 To explore the prognostic impact and clinical application value of therapeutic plasma exchange(TPE) intervention timing and liver injury periodization in patients with exertional heat stroke(EHS). 【Methods】 Data of 127 EHS patients from the First Medical Center of the General Hospital of the People′s Liberation Army from January 2011 to December 2023 were collected, then divided into the death group and the survival group based on therapeutic outcomes and into 5 stages according to the dynamic changes of ALT, AST, TBIL and DBIL. According to propensity score matching analysis, 11 patients in the survival group and 12 patients in the death group were included in the statistical analysis, and 20 of them were treated with TPE. The changes in indicators and clinical outcomes before and after TPE were observed, in order to evaluate the impact of intervention timing on prognosis. 【Results】 Among the 23 patients, 14 had no liver injury or could progress to the repair phase, resulting in 3 deaths(with the mortality rate of 21.43%), while 9 patients failed to progress to the repair phase, resulting in 9 deaths(with the mortality rate of 100%), with significant differences(P<0.05). The mortality rate of the first TPE intervention before the third stage of liver injury was 23.08%(3/13), while that of intervention after reaching or exceeding the third stage was 85.71%(6/7), and the difference was statistically significant(P<0.05). 【Conclusion】 TPE should be executed actively in EHS patients combined with liver injury before the third phase to lock its pathological and physiological processes, thereby improving prognosis and reducing mortality.
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【Objective】 To review the occurrence of allergic reactions during therapeutic plasma exchange (TPE) and to explore the risk factors of TPE allergic reactions. 【Methods】 The clinical data of 929 patients treated with TPE using plasma components by the Department of Transfusion Medicine in our medical center from 2018 to 2023 were collected. The influencing factors of allergic reactions were analyzed by univariate analysis, and the independent risk factors of allergic reactions were analyzed by logistic multivariate regression analysis. 【Results】 A total of 4 071 TPEs were performed in 929 patients.Among them, 198 patients (21.31%) experienced 349 times (8.57%) of allergic reactions, with the incidence of grade Ⅰ, Ⅱ and Ⅲ allergic reactions of 16.33%, 81.38% and 2.29%, respectively, and no deaths. The univariate analysis showed that the patient′s age, allergy history, diagnosis of immune-related diseases, ICU admission, plasma consumption, total blood volume, maximum blood flow rate and combined use of albumin were related to the occurrence of allergic reactions (P<0.05). Multivariate regression analysis showed that young patients, a history of allergy, immune-related diseases and non-ICU patients were prone to allergic reactions in TPE, but the treatment options of TPE such as substitute fluid category, plasma consumption and blood flow rate were not related to the occurrence of allergic reactions. 【Conclusion】 There are significant individual differences in the occurrence of allergic reactions for TPE, and young age, history of allergies, immune-related diseases and non-ICU patients are risk factors for allergic reactions in TPE. Identifying patients with risk factors before TPE treatment and giving corresponding preventive measures can reduce the incidence of allergic reactions.
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Elemene, derived from Curcuma wenyujin, one of the "8 famous genuine medicinal materials of Zhejiang province," exhibits remarkable antitumor activity. It has gained wide recognition in clinical practice for effectiveness on tumors. Dr. XIE Tian, introduced the innovative concept of "molecular compatibility theory" by combining Chinese medicine principles, specifically the "monarch, minister, assistant, and envoy" theory, with modern biomedical technology. This groundbreaking approach, along with a systematic analysis of Chinese medicine and modern biomedical knowledge, led to the development of elemene nanoliposome formulations. These novel formulations offer numerous advantages, including low toxicity, well-defined composition, synergistic effects on multiple targets, and excellent biocompatibility. Following the principles of the "molecular compatibility theory", further exploration of cancer treatment strategies and methods based on elemene was undertaken. This comprehensive review consolidates the current understanding of elemene's potential antitumor mechanisms, recent clinical investigations, advancements in drug delivery systems, and structural modifications. The ultimate goal of this review is to establish a solid theoretical foundation for researchers, empowering them to develop more effective antitumor drugs based on the principles of "molecular compatibility theory".
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Humans , Retrospective Studies , Antineoplastic Agents/therapeutic use , Neoplasms/drug therapy , Drugs, Chinese Herbal/therapeutic use , Sesquiterpenes/therapeutic useSubject(s)
Health Literacy , Humans , China/epidemiology , Health Status , Mental Health , Poverty , Surveys and QuestionnairesABSTRACT
BACKGROUND: Due to the increasing recognition of gastrointestinal stromal tumor (GIST), novel insights have appeared in both preclinical and clinical research and begun to reshape the field. This study aims to map the research landscape through bibliometric analysis and provide a brief overview for the future of the GIST field. METHODS: We searched the Web of Science Core Collection without publication data restrictions for GISTs and performed a bibliometric analysis with CiteSpace and VOSviewer software. RESULTS: In sum, 5,911 of 13,776 records were included, and these studies were published in 948 journals and written by 24,965 authors from 4,633 institutions in 100 countries. Referring to published reviews and bibliometric analysis, we classified the future trends in four groups. In epidemiological study, precise incidence and clinicopathological features in different regions and races might become potential hotspots. Novel therapy, such as drugs, modified strategies, radioligand therapy, was persistent hotspots in GIST fields, and ctDNA-guided diagnosis, monitoring, and treatment might meet future clinical needs. The debate over serosa surgery vs. mucosa surgery will remain active for a long time in GIST surgery, and function reserve surgery, biology-based surgery will play an important role in future. Moreover, rare GIST type, like NF-1-associated GIST, Carney triads and SDH mutant GIST, need more studies in pathogenesis and genetic mutation to provide appropriate treatment for this orphan GIST patients. CONCLUSIONS: Potential hotspots in future GIST trends might involve epidemiology, agents, resection therapy and rare type GIST, moreover, researchers could pay more attention in these four fields.
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Gastrointestinal Stromal Tumors , Humans , Gastrointestinal Stromal Tumors/epidemiology , Gastrointestinal Stromal Tumors/genetics , Gastrointestinal Stromal Tumors/therapy , Bibliometrics , MutationABSTRACT
AIM: To investigate the mechanism of pyrrolidine dithiocarbamate(PDTC)on transforming growth factor-beta 2(TGF-β2)-induced epithelial-mesenchymal transition(EMT)in human lens epithelial cells(LECs).METHODS: LECs were treated with various doses of PDTC chemicals following TGF-β2 caused EMT on these cells. Cell proliferation and lateral migration were discovered using the CCK-8 and cell scratch test. The markers of EMT, including E-cadherin, α-SMA and nuclear factor-κB(NF-κB)signaling pathway-related expression, were tested by Western Blot as well as the changes in the expression of the apoptosis-related proteins BAX, BCL-2, Caspase-3, and Cyclin D1.RESULTS: The proliferation and migration viability of cells in the TGF-β2 treated group was increased compared to the group without TGF-β2, and the expression of α-SMA increased whereas the E-cadherin expression decreased. With the effect of TGF-β2, NF-κB p65 and phosphorylated NF-κB p65 expression increased, the concentration of TGF-β2 that had the greatest capacity for proliferation and migration was 10 ng/mL(P<0.05). Mechanism study of PDTC-induced EMT reversal and apoptosis showed that cell viability and migratory capability were both significantly reduced after PDTC intervention; PDTC prevents IκB phosphorylation, thus inhibiting NF-κB nuclear translocation. Protein associated to the NF-κB signaling pathway, and protein expression of NF-κB/IκBα/p-IκBα/Iκκ-α/p-Iκκ-α was decreased(P<0.05), PDTC increased the expression of the pro-apoptotic protein BAX/Caspase-3, expression of the inhibitor of apoptosis protein BCL-2 and the cell cycle protein Cyclin D1 was reduced. The expression of NF-κB/IκB mRNA was reduced, expression of the apoptosis-related mRNA BAX increased, while BCL-2 reduced.CONCLUSION: The EMT in LECs cells induced by TGF-β2 can be significantly reversed by PDTC, which may be related to the decreased expression of NF-κB p65/IκB/Iκκ-α and activation of apoptosis-related protein. PDTC can reverse EMT by inhibiting NF-κB signaling pathway and induce apoptosis of abnormally proliferated cells, which will provide new potential therapeutic agents for posterior capsular opacification(PCO)treatment.
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Cryptococcus gattii is a kind of Cryptococcus that infects the lungs and central nervous system through the inhalation of infectious particles such as spores or Cryptococcus yeast cells. The development of clinical disease of Cryptococcus gattii may be determined by the sex, immunity and genetics of the host factors, in which immune system factors play an important role in host injury. Their defects will have serious clinical consequences. Cryptococcus gattii mainly infects the population with normal immune, and the infection of immunosuppressed population is rare. The infection mechanism, molecular types, clinical characteristics, treatment and prognosis of Cryptococcus gattii meningitis were different between the two populations. This article reviews the main differences in different immune status with Cryptococcus gattii meningitis.
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OBJECTIVE To provide feasible regulatory paths for the online sales supervision of Chinese medicinal materials from the perspective of the characteristics of new online sales and the characteristics of Chinese medicinal materials. METHODS Through the investigation of the sales form of Chinese medicinal materials on the e-commerce platform and the search of Chinese medicinal materials online dispute cases, the difficulties and existing problems in the supervision of Chinese medicinal materials under the new online sales model were analyzed, and corresponding countermeasures were proposed. RESULTS & CONCLUSIONS Clarifying the conceptual boundary between Chinese medicinal materials and their decoction pieces, agricultural products and food is the key to standardizing the online sale of Chinese medicinal materials. The regulatory criteria, which determine whether Chinese medicinal materials belong to drug management based on whether they had been included in medicinal channels, didn’t consider the diversity of online sales channels for Chinese medicinal materials, their safety and the disguised sales of Chinese herbal decoction pieces. It is necessary to establish the concept of hierarchical management of Chinese medicinal materials, strictly restrict the behavior of claiming the efficacy of Chinese medicinal materials and selling Chinese herbal decoction pieces in live streaming, improve the defining path of false propaganda of Chinese medicinal materials, implement the responsibilities and obligations of live streaming marketing subjects and platforms, and safeguard the legitimate rights of consumers.
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Objective:To explore the efficacy and safety of blinatumomab in treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL).Methods:The data of 8 patients with relapsed/refractory B-ALL treated with blinatumomab in Shanghai Zhaxin Traditional Chinese and Western Medicine Hospital from September 2020 to December 2021 were retrospectively analyzed, and their clinical characteristics, overall survival, lymphocyte subsets, cytokines, tandem transplantation and adverse reactions were analyzed.Results:The median follow-up time of 8 patients was 143 d (range: 41-534 d). Five of the 8 patients were alive; among them, 4 of 6 patients assessed to be in minimal residual disease (MRD)-negative complete remission (CR) and 1 of 2 patients assessed to be in non-remission at the time of belintuzumab discontinuation were alive. The median duration of treatment with belintuzumab was 28 d (10-56 d), and it was 23 d (10-56 d) for patients with MRD-positive at baseline and 28 d (25-31 d) for the 4 non-remission patients. Six patients achieved MRD-negative CR after treatment, of which 4 were assessed as MRD-positive at baseline and 2 were assessed as non-remission at baseline. All 4 patients with MRD-positive CR achieved MRD-negative CR after treatment with belintuzumab, including 1 patient with Philadelphia chromosome-positive (Ph +) ALL bridged to autologous hematopoietic stem cell transplantation, and 1 patient with Ph + ALL and 1 patient with Ph - ALL received sequential allogeneic hematopoietic stem cell transplantation and had persistent MRD-negative CR. Two of the 4 non-remission patients achieved MRD-negative CR after treatment with belintuzumab, including 1 patient with Ph + ALL bridged to autologous hematopoietic stem cell transplantation, and 1 patient with Ph - ALL received sequential allogeneic hematopoietic stem cell transplantation, and the 2 patients had persistent MRD-negative CR. Leukocyte counts and neutrophils decreased in both MRD-positive CR and non-remission patients after receiving belintumomab. The proportion and absolute number of CD3 + T and CD3 + CD8 + T lymphocytes in patients with MRD-positive CR were higher than those in patients without remission, and both decreased after drug administration. Median interleukin-6 (46.23, 1.42 pg/ml), interleukin-8 (17.85, 2.10 pg/ml), interleukin-10 (7.43, 1.49 pg/ml) and interferon-γ (11.82, 0.39 pg/ml) levels were elevated in MRD-positive CR and non-remission patients at week 3 of treatment. Grade 1 cytokine release syndrome occurred in 1 case with clinical manifestations of fever, which improved after drug suspension. Three cases developed infections, 2 of which were pulmonary and 1 of which was upper respiratory tract infection. No immune effector cell-associated neurotoxic syndrome was observed. Conclusions:Belintumomab is effective for MRD clearance in relapsed/refractory B-ALL with manageable adverse reactions, providing an effective therapeutic option for bridging hematopoietic stem cell transplantation to prolong the survival of patients.
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Objective To explore the residual level of FPMs in indoor dust samples in Shenzhen from 2020 and 2021, and to analyze its temporal distribution characteristics. Methods In the present study, indoor dust samples (n=193) from residential buildings in Shenzhen. were collected to analyze the temporal variation characteristics of FPMs. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was applied to determine the concentrations of FP and its four major metabolites (fipronil-sulfone, fipronil-sulfide, fipronil-desulfinyl, and fipronil-amide; abbreviated as FP-SFO, FP-SFI, FP-DES, and FP-AM) in the samples. The sum of the concentrations of FP and its four metabolites was represented as additive mass concentration (ΣFPMs). Additionaly, Wilcoxon test was performed to determine the temporal distribution differences of FPMs’ concentrations. Results From 2020 to 2021, the concentration of ΣFPMs for the in door dust samples in Shenzhen ranged from 0.51 to 4 415 ng/g (median: 18.8ng/g). FP, FP-SFO AND FP-SFI were the major target analytes in the sample with detection rates of 90.60%,86.20% and 75.40%, respectively. The detection rates of other metabolites were low (≤ 44.3%). Analysis of the temporal variation trend of FPMs’ concentrations showed that there was no significant difference in the levels of ΣFPMs between warm season(spring and summer)and cold season(autumn and winter)in the indoor dust samples from 2020 to 2021(2.38 vs 2.84ng/g , P > 0.05). However , the concentrations of FP-SFI and ΣFPMs in the indoor dust samples collected from 2021 showed an significantly increasing trend compared with 2020(1.02 vs 1.89 , 17.80vs. 20.10 ng/g , P < 0.05). Conclusion From 2020 to 2021 , the detection level of FPMs in indoor dust in Shenzhen is relatively high and shows an upward trend , with no obvious seasonal difference. However, whether the residual level of FPMs in indoor dust poses a risk to human health needs further study.