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Tenofovir disoproxil fumarate （TDF） is a first-line treatment for chronic hepatitis B. With increasing use worldwide， the adverse events of renal injury caused by this drug have also attracted industry attention. This article reports a 61- year-old patient with liver cancer complicated with hepatitis B virus （HBV） infection. The patient started using TDF in mid-March 2022 and developed kidney injury after 2 months of treatment， during which he received 2 courses of donafenib combined with sintilimab chemotherapy and irregular administration of diclofenac for pain relief. In this paper， Naranjo’s assessment scale was used to evaluate the drugs that may be associated with renal injury， including TDF and sintilimab， and the drugs that are suspected to be associated with renal injury are donafenib and diclofenac. The renal injury caused by TDF can be judged according to the changes in the patient’s condition， the incidence of drug-induced renal injury， clinical manifestations， occurrence time， occurrence mechanism， drug combination， and high-risk factors. The changes of serum creatinine in patients with liver cancer complicated with HBV infection after TDF should be dynamically monitored in the clinic， and the dose of antiviral drugs should be adjusted if necessary and other antiviral drugs with less impact on renal function can be selected， to provide individualized medication recommendations for tumor patients， reduce the incidence of TDF-related renal injury.
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@#Objective To compare the safety and efficacy of the da Vinci robot and thoracoscopic subxiphoid approach for the treatment of anterior mediastinal tumors. Methods The clinical data of patients who underwent anterior mediastinal tumor resection through the subxiphoid approach admitted to the same medical group in the Department of Thoracic Surgery of the First Hospital of Lanzhou University between June 2020 and April 2022 were retrospectively analyzed. According to the surgery approach, the patients were divided into a robot-assisted thoracoscopic surgery (RATS) group and a video-assisted thoracoscopic surgery (VATS) group. The perioperative data and the incidence of postoperative complications were compared between the two groups. Results A total of 79 patients were enrolled. There were 41 patients in the RATS group, including 13 males and 28 females, with an average age of 45.61±14.99 years. There were 38 patients in the VATS group, including 14 males and 24 females, with an average age of 47.84±15.05 years. All patients completed the surgery successfully. Hospitalization cost and operative time were higher or longer in the RATS group than those in the VATS group, and the difference was statistically significant (P<0.05). Intraoperative bleeding, postoperative hospital stay, postoperative water and food intake time, postoperative off-bed activity time, white blood cell count, neutrophil percentage and visual analogue scale (VAS) score on the first postoperative day, white blood cell count and neutrophil percentage on the third postoperative day, duration of analgesic pump use, the number of voluntary compressions of the analgesic pump, and mediastinal drainage volume were all superior to those in the VATS group (P<0.05). The differences in VAS scores on the third postoperative day, duration of drainage tube retention and postoperative complication rates were not statistically different between the two groups (P>0.05). Conclusion RATS subxiphoid anterior mediastinum tumor resection is a safe and feasible surgical method with less injury and higher safety, which is conducive to rapid postoperative recovery and has wide clinical application prospects.
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Objective: To investigate the clinicopathological features, diagnosis and differential diagnosis of adrenal cortical carcinoma (ACC) in children. Methods: Twenty-five children with ACC diagnosed in the Department of Pathology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China from March 2014 to August 2022 were retrospectively analyzed. The related literature was reviewed. Results: A total of 25 children with ACC were collected, including 11 males and 14 females, with a male to female ratio of 1.0∶1.3. The patient ages ranged from 8 months to 14 years (median, 4 years). Eighteen cases with clinical data had functional tumors (18/22, 81.8%) presenting with virilization or precocious puberty (15/18), symptoms related to hypercortisolism (8/18) or endocrine symptoms mixed with both (5/18), while 3 cases (3/22, 13.6%) had unknown clinical data. The clinical manifestations of four patients with nonfunctional tumors were an abdominal mass and/or abdominal pain, walking instability and others. Grossly, the average maximum diameter of the tumor was 9.4 cm. Most of the tumors were nodular and partially encapsuled. The cut surfaces were gray or gray brown, soft with hemorrhage. Histologically, the tumor cells were diffusely distributed, separated by a vascular-rich network. The tumor cells were large, with distinct nucleoli, abundant eosinophilic or clear cytoplasm, and round or oval nuclei. The mitotic index was high, and atypical mitoses were common. Necrosis, calcification, capsule invasion or/and venous invasion were present. In some cases, the tumor invaded the surrounding soft tissues or kidneys. Immunohistochemically, the tumor cells were diffusely positive for syn and SF1 and focally positive for α-inhibin, Melan A and Calretinin, but negative for CgA. Ki-67 proliferation index ranged from 2%-90%. TP53 gene status was examined in 7 cases, in which mutations were detected in 4 cases. Follow-up data was obtained in 21 patients, among whom 18 received chemotherapy and 3 received radiotherapy. Distant metastasis occurred in 13 patients. Median progression-free survival (PFS) was 11.2 months and median overall survival (OS) was 54.7 months. Patients aged less than 5 years had a better prognosis for OS (P<0.05) than the older ones (≥5 years), but a similar PFS (P>0.05). Male patients and Ki-67 proliferation index <15% had a better prognosis tendency for OS, but there was no statistically significant difference (P>0.05). Conclusions: ACC in children is a rare, often functional tumor associated with Li-Fraumeni genetic syndrome and has a poor prognosis. Diagnosis and differential diagnosis require a combination of morphological, phenotypic and clinical analysis.
Subject(s)
Child , Humans , Male , Female , Infant , Adrenocortical Carcinoma , Retrospective Studies , Ki-67 Antigen , China , Adrenal Cortex NeoplasmsABSTRACT
The FRUITFULL (FUL) gene belongs to the AP1/ FUL subfamily of the plant MADS-box family and has functions in regulating flowering time, floral meristem differentiation and fruit development. PfFUL gene sequence was derived from the perilla transcriptome data, and the basic physicochemical properties of PfFUL were analyzed by bioinformatics methods. Evolutionary relationships of PfFUL with other species of FUL were analyzed by phylogenetic tree. Plant expression vector 35S::PfFUL was constructed and used to transform wild type Col-0 and mutant ful-7 Arabidopsis to obtain overexpression 35S::PfFUL/ Col-0 and complemented mutation 35S::PfFUL / ful-7 plants respectively. Comparative phenotypic analysis was performed to preliminarily clarify the function of PfFUL gene in plant flowering and fruit development. The functions of the PfFUL gene during flowering and angular fruit development of the plants were initially clarified. The CDS of PfFUL gene is 738 bp and encodes 245 amino acids. Phylogenetic tree showed that the perilla PfFUL was closely related to Solanum lycopersicum, Salvia splendens and Salvia hispanica, but far related to Arabidopsis thaliana, Nicotiana tabacum and Vitis vinifera. Compared to Col-0 and ful-7, the transgenic plants showed early flowering (P0. 05), and the amount of wrinkled seed was significantly reduced (P<0. 01). In addition, phenotypic observations revealed that the transgenic plants also exhibited increased internode length and narrowed and curled cauline leaves. In conclusion, this study confirmed that the PfFUL gene regulates early flowering and fruit development in plants and participates in nutritional growth.
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Objective To study whether bergapten (BG) protects PC12 cells from oxygen-glucose deprivation (OGD) induced cell injury by regulating long non-coding RNA (lncRNA) opioid receptor gene (Oprm1) expression. Methods PC12 cells were divided into control (Con) group, OGD group, OGD+ low concentration BG (BG-L) group, OGD+medium concentration BG (BG-M) group, OGD + high concentration BG (BG-H) group, OGD + pcDNA group, OGD+pcDNA-Oprm1 group, OGD+BG+si-NC group, OGD+BG+si-Oprm1 group. The malondialdehyde (MDA) content, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were measured by the kits. Cell apoptosis rate was analysed by flow cytometry. The expression level of Oprm1 was analysed by Real-time PCR. Results Compared with the Con group, the apoptosis rate and MDA content of PC12 cells in OGD group increased significantly, whereas Oprm1 expression, SOD and GSH-Px activity decreased significantly (P < 0. 05). Compared with the OGD group, the apoptosis rate and MDA content of PC12 cells in the OGD + BG-L group, OGD + BG-M group, OGD + BG-H group were significantly reduced, whereas the Oprm1 expression, SOD and GSH-Px activities increased significantly (P < 0. 05). Compared with the OGD+pcDNA group, the apoptosis rate and MDA content of the PC12 cells in the OGD+pcDNA-Oprm1 group reduced significantly, whereas the SOD and GSH-Px activities increased significantly (P<0. 05). Compared with the OGD+BG+si-NC group, the apoptosis rate and MDA content of PC12 cells in the OGD+BG+si-Oprm1 group increased significantly, whereas the SOD and GSH-Px activities decreased significantly (P < 0. 05). Conclusion Bergapten may alleviate OGD-induced PC12 cell injury, which is correlated to the up-regulation of lncRNA Oprm1 expression.
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Energy imbalance is eonsidered an important driver of human diseases. As an important energy sensor, AMPK plays a central role in maintaining energy homeostasis, making it a key target for disease prévention and treatment. As a new type of cell death, ferroptosis is related to the pathophysiologieal process of many diseases, and AMPK-related signaling pathway is an important way to regulate iron death. Understanding which pathway AMPK induces or inhibits ferroptosis will provide new ideas for the treatment of diseases in the future and provide new targets for new drug research. In this paper, we review the related litera-tures and explore the signaling pathways of AMPK regulating ferroptosis, wïth a brief description of the application of AMPK-mediated ferroptosis related signaling pathways in diseases, hoping to provide reference for later research.
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Objective: To identify BRAF V600E mutations in adult Wilms tumor (WT) with overlapping histologic features of metanephric adenoma (MA) and to investigate the clinicopathological features of adult WT. Methods: The clinical features of adult WT diagnosed at the Fudan University Shanghai Cancer Center, Shanghai, China from 2012 to 2021 were reviewed. HE-stained slides of all cases were reviewed by 2 expert pathologists. Representative tissues were selected for BRAF V600E immunohistochemical (IHC) staining and gene sequencing. Results: In adult WT with MA-like areas (cohort Ⅰ, n=6), 5 of the 6 cases were composed of epithelial-predominant and were positive for WT-1 and CD56, respectively, and all were positive for CD57. All 6 cases revealed highly variable Ki-67 indices, ranging from 1% in some areas to 60% in others. 5 of the 6 cases harbored a BRAF V600E mutation. All cases in cohort I were followed up for 23 to 71 months, and all survived. In classical adult WT without MA-like areas cohort (cohort Ⅱ, n=13), all 7 cases with available material were negative for BRAF by IHC and none of them had any BRAF mutation. Conclusions: BRAF V600E mutations are frequently present in adult WT with overlapping morphologically features of MA, but not in those without. More importantly, adult WTs with overlapping histologic features of MA may be an intermediate entity between typical MA and WT that may have a favorable prognosis and possible therapeutic targets.
Subject(s)
Adult , Humans , Proto-Oncogene Proteins B-raf/genetics , China , Wilms Tumor/genetics , Kidney Neoplasms/pathology , Mutation , Adenoma/genetics , Biomarkers, Tumor/geneticsABSTRACT
OBJECTIVE@#This work explores the impact of electroacupuncture (EA) on acute postoperative pain (APP) and the role of stimulator of interferon genes/type-1 interferon (STING/IFN-1) signaling pathway modulation in the analgesic effect of EA in APP rats.@*METHODS@#The APP rat model was initiated through abdominal surgery and the animals received two 30 min sessions of EA at bilateral ST36 (Zusanli) and SP6 (Sanyinjiao) acupoints. Mechanical, thermal and cold sensitivity tests were performed to measure the pain threshold, and electroencephalograms were recorded in the primary somatosensory cortex to identify the effects of EA treatment on APP. Western blotting and immunofluorescence were used to examine the expression and distribution of proteins in the STING/IFN-1 pathway as well as neuroinflammation. A STING inhibitor (C-176) was administered intrathecally to verify its role in EA.@*RESULTS@#APP rats displayed mechanical and thermal hypersensitivities compared to the control group (P < 0.05). APP significantly reduced the amplitude of θ, α and γ oscillations compared to their baseline values (P < 0.05). Interestingly, expression levels of proteins in the STING/IFN-1 pathway were downregulated after inducing APP (P < 0.05). Further, APP increased pro-inflammatory factors, including interleukin-6, tumor necrosis factor-α and inducible nitric oxide synthase, and downregulated anti-inflammatory factors, including interleukin-10 and arginase-1 (P < 0.05). EA effectively attenuated APP-induced painful hypersensitivities (P < 0.05) and restored the θ, α and γ power in APP rats (P < 0.05). Meanwhile, EA distinctly activated the STING/IFN-1 pathway and mitigated the neuroinflammatory response (P < 0.05). Furthermore, STING/IFN-1 was predominantly expressed in isolectin-B4- or calcitonin-gene-related-peptide-labeled dorsal root ganglion neurons and superficial laminae of the spinal dorsal horn. Inhibition of the STING/IFN-1 pathway by intrathecal injection of C-176 weakened the analgesic and anti-inflammatory effects of EA on APP (P < 0.05).@*CONCLUSION@#EA can generate robust analgesic and anti-inflammatory effects on APP, and these effects may be linked to activating the STING/IFN-1 pathway, suggesting that STING/IFN-1 may be a target for relieving APP. Please cite this article as: Ding YY, Xu F, Wang YF, Han LL, Huang SQ, Zhao S, Ma LL, Zhang TH, Zhao WJ, Chen XD. Electroacupuncture alleviates postoperative pain through inhibiting neuroinflammation via stimulator of interferon genes/type-1 interferon pathway. J Integr Med. 2023; 21(5): 496-508.
Subject(s)
Rats , Animals , Rats, Sprague-Dawley , Neuroinflammatory Diseases , Electroacupuncture , Pain, Postoperative , InterferonsABSTRACT
Rheumatoid arthritis （RA） is a refractory autoimmune disease that can cause symmetrical polyarticular disease. The key mechanism of its occurrence and development is the dysequilibrium of helper T cell 17 （Th17）/regulatory T cell （Treg） balance. Therefore， reconstructing Th17/Treg balance may be a new strategy for the treatment of RA. Traditional Chinese medicine has significant advantages in the treatment of RA such as integrity， multi-target， multi-link and multi-path. This paper summarizes the basic and clinical studies on the regulation of Th17/Treg balance in the treatment of RA by traditional Chinese medicine in the past five years， and finds that the active components/sites of traditional Chinese medicine such as flavonoids， alkaloids and terpenes have unique advantages in the regulation of Th17/Treg balance. The traditional Chinese medicine compound formula interferes with Th17/Treg balance by exerting the effects of dispelling wind， dehumidifying， removing blood stasis， unblocking collaterals， relieving pain， dispersing cold and strengthening health. The effect of external treatment of traditional Chinese medicine is obvious and can be used as a clinical adjuvant therapy for RA； related mechanisms of action include regulating the production of inflammatory factors， regulating the expression of transcription factors and interfering with the activation of signaling pathways. However， the existing research has the shortcomings of insufficient mechanism research， few clinical research， limited external treatment research of traditional Chinese medicine， and lack of combination therapy research， which need to be improved by follow- up research.
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Ferroptosis is a new type of programmed cell death different from other cell death pathways such as apoptosis,autophagy,necrosis,and pyroptosis in terms of initiation,mechanisms,and molecular characteristics.As the accumulation of phospholipid hydroperoxides is the hallmark of ferroptosis,the balance between oxidative damage and antioxidant defense is critical to the regulatory mechanism of ferroptosis.In cancer,the upregulation of antioxidant defense pathways can inhibit ferroptosis,thereby promoting cancer cells to survive the oxidative stress and develop drug resistance.This review systematically introduces the main features and regulatory mechanisms of ferroptosis.In addition,we summarize the role of ferroptosis in the progression and drug resistance of malignant tumors,providing novel implications for further research on the pathogenesis of malignant tumors and discovery of new targets for anti-cancer therapy.
Subject(s)
Humans , Ferroptosis , Antioxidants , Apoptosis , Neoplasms , AutophagyABSTRACT
This study aimed to explore the expression changes of VASA gene in sheep testis development and to construct VASA gene knock-in vector to prepare for the study on the differentiation of sheep germ cells in vitro. The testicular tissues of 3-month-old (3M) and 9-month-old (9M) sheep which represent immature and mature stages, respectively, were collected. The differential expression of VASA gene was analyzed by quantitative real-time PCR (qPCR) and Western blotting, and the location of VASA gene was detected by immunohistochemistry. The sgRNA targeting the VASA gene was designed and homologous recombination vectors were constructed by PCR. Subsequently, plasmids were transferred into sheep ear fibroblasts. The VASA gene was activated in combination with CRISPR/dCas9 technology to further verify the efficiency of the vector. The results showed that the expression level of VASA gene increased significantly with the development of sheep testis (P < 0.01), and was mainly located in spermatocytes and round spermatids. The knock-in vector of VASA gene was constructed by CRISPR/Cas9 system, and the Cas9-gRNA vector and pEGFP-PGK puro-VASA vector were transfected into ear fibroblasts. After CRISPR/dCas9 system was activated, ear fibroblasts successfully expressed VASA gene. The results suggest that VASA gene plays a potential function in sheep testicular development and spermatogenesis, and the VASA gene knock-in vector can be constructed in vitro through the CRISPR/Cas9 system. Our results provided effective research tools for further research of germ cell development and differentiation.
Subject(s)
Male , Animals , Sheep/genetics , CRISPR-Cas Systems/genetics , Gene Knock-In Techniques , RNA, Guide, CRISPR-Cas Systems , Plasmids , Germ CellsABSTRACT
OBJECTIVES@#To investigate the cerebral metabolism in the patients with type 2 diabetes mellitus-associated cognitive dysfunction (T2DACD) and explore the mechanism of electroacupuncture (EA) at the acupoints for Tiaozang Xingshen (adjusting zangfu function and rescuing the spirit) in treatment of T2DACD, using magnetic resonance spectroscopy.@*METHODS@#Fifteen patients with T2DACD (observation group) and 22 healthy subjects (control group) were enrolled. In the observation group, the patients were treated with EA for Tiaozang Xingshen at Baihui (GV 20) and Shenting (GV 24), and bilateral Feishu (BL 13), Pishu (BL 20), Shenshu (BL 23), Zusanli (ST 36), Sanyinjiao (SP 6), Hegu (LI 4) and Taichong (LR 3). EA was operated with disperse-dense wave, 2 Hz/100 Hz in frequency and 0.1 mA to 1.0 mA in current intensity; 30 min each time, once daily. One course of EA consisted of 5 treatments, at the interval of 2 days and the intervention lasted 8 courses. Before treatment in the control group, before and after treatment in the observation group, the score of Montreal cognitive assessment scale (MoCA), the score of clinical dementia rating (CDR), Flanker paradigm, Stroop paradigm, Nback paradigm, the score of self-rating anxiety scale (SAS), the score of self-rating depression scale (SDS), and the score of Hamilton depression rating scale (HAMD) were evaluated separately; the glycolipid metabolic indexes (fasting plasma glucose [FPG], glycosylated hemoglobin type A1c [HbA1c], total cholesterol [TC], triacylglycerol [TG], high-density lipoprotein cholesterol [HDL-C] and low-density lipoprotein cholesterol [LDL-C]) were determined；with the magnetic resonance spectroscopy technique adopted, the metabolites in the basal ganglia area were detected. The correlation analysis was performed for the metabolite values with MoCA score, CDR score , Flanker paradigm, Stroop paradigm, and Nback paradigm.@*RESULTS@#Before treatment, compared with the control group, in the observation group, MoCA score was lower (P<0.001), CDR score and the levels of FPG and HbA1c were higher (P<0.001); the reaction times of Flanker non-conflict, Flanker conflict, Stroop neutrality, Stroop congruence, Stroop conflict, and 1-back were prolonged (P<0.05, P<0.001), and the accuracy of Flanker conflict, Stroop conflict, and 1-back decreased (P<0.05, P<0.01); the ratio of N-acetyl aspartate (NAA) to creatine (Cr) in the left basal ganglia area was dropped (P<0.001), and that of myo-inositol (MI) to Cr in the right side increased (P<0.05). In the observation group after treatment, compared with the levels before treatment, MoCA score was higher (P<0.001), the scores of CDR, SAS and HAMD were reduced (P<0.01, P<0.05), the reaction times of Flanker conflict and Stroop conflict shortened (P<0.001, P<0.05), and the accuracy of Flanker conflict and 1-back increased (P<0.001, P<0.05); the ratio of NAA to Cr in the left basal ganglia area and that of the gamma-aminobutyric acid (GABA) to Cr in the right increased (P<0.05), that of MI to Cr in the right decreased (P<0.05). Before treatment, in the observation group, the ratio of MI to Cr in the right basal ganglia area was positively correlated with the reaction time of Stroop congruence (r=0.671, P=0.012) and this ratio was positively correlated with the reaction time of Stroop conflict (r=0.576, P=0.039).@*CONCLUSIONS@#Electroacupuncture for "adjusting zangfu function and rescuing the mind" improves the cognitive function of T2DACD patients, which may be related to the regulation of NAA, MI and GABA levels in the basal ganglia.
Subject(s)
Humans , Electroacupuncture , Acupuncture Therapy , Acupuncture Points , Diabetes Mellitus, Type 2/therapy , Glycated Hemoglobin , Cognitive Dysfunction/therapy , Cholesterol , gamma-Aminobutyric AcidABSTRACT
OBJECTIVE@#To compare the clinical effect of conventional acupuncture combined with pricking and cupping at Jianbo area and conventional acupuncture in the treatment of scapulohumeral periarthritis of frozen stage.@*METHODS@#A total of 66 patients with scapulohumeral periarthritis of frozen stage were randomly divided into a combination group (31 cases) and an acupuncture group (35 cases, 1 case dropped off). Both groups were given functional exercise. Patients in the acupuncture group were treated with acupuncture at Jianyu (LI 15), Jianliao (TE 14), Binao (LI 14) and ashi point on the affected side, once every other day, three times a week, for a total of 4 weeks. On the basis of treatment in the acupuncture group, the patients in the combination group were treated with pricking and cupping at Jianbo area (the area surrounded by the 3 acupoints of Tianzong [SI 11], Naoshu [SI 10] and Jianzhen [SI 9]), once a week for 4 weeks. The University of California-Los Angeles (UCLA) shoulder joint score, visual analogue scale (VAS) score before treatment, after treatment and after 6 months of treatment completion (follow-up) and tenderness threshold before and after treatment, and the clinical effects of the two groups after treatment and in follow-up were evaluated.@*RESULTS@#In the two groups, after treatment and in follow-up, the UCLA shoulder joint scores were higher than those before treatment (P<0.05), and the VAS scores were lower than those before treatment (P<0.05). In the combination group, after treatment and in follow-up, the UCLA shoulder joint score was higher than that of the acupuncture group (P<0.05), and the VAS score was lower than that of the acupuncture group (P<0.05). After treatment, the tenderness thresholds of the two groups were higher than those before treatment (P<0.05), and the tenderness threshold in the combination group was higher than that in the acupuncture group (P<0.05). After treatment and in follow-up, the cured and markedly effective rate of the combination group was 48.4% (15/31) and 51.6% (16/31) respectively, which was higher than 23.5% (8/34) and 23.5% (8/34) of the acupuncture group (P<0.05).@*CONCLUSION@#Pricking and cupping in Jianbo area combined with conventional acupuncture can improve shoulder joint function and relieve shoulder joint pain in patients with scapulohumeral periarthritis of frozen stage, and the curative effect is better than that of single conventional acupuncture.
Subject(s)
Humans , Periarthritis/therapy , Acupuncture Therapy , Shoulder Pain/therapy , Shoulder Joint , Acupuncture Points , Treatment OutcomeABSTRACT
Monoclonal antibody drugs that inhibit programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) have been widely used in esophageal cancer (EC) and yielded significant therapeutic responses. However, only a few patients obtain lasting clinical benefits due to primary or acquired drug resistance, and new treatment schemes are urgently needed. The tumor immune microenvironment is the main factor that affects patients' response to immunosuppressive agents. This article will discuss the role of immunosuppressive cells and non-cellular components in the immune process to provide ideas for the next research direction of EC.
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OBJECTIVE@#To detect the expression level of HK2 gene in the bone marrow of newly diagnosed patients with acute myeloid leukemia (AML) and investigate its influence on the clinical characteristics and prognosis.@*METHODS@#The expression level of HK2 gene in the bone marrow of 90 newly diagnosed patients with AML that accompanying clinical characteristics and survival status were detected by RT-qPCR, and compared with 18 allogeneic hematopoietic stem cell transplantation (allo-HSCT) donors. The Chi-square test, Kaplan-Meier survival analysis, and Cox proportional hazards regression model were used to analyze the correlation of HK2 expression level with clinical characteristics and prognosis.@*RESULTS@#Compared with allo-HSCT donors, the HK2 expression was significantly increased in newly diagnosed AML patients (P <0.01). Compared with patients with total response (OR, complete response + complete response with incomplete hematologic recovery) after 2 courses of induction chemotherapy, the expression of HK2 in patients without OR was significantly increased (P <0.05). There was a significant difference in the relative expression of HK2 between patients with and without OR after 2 courses of induction therapy (P <0.001). The median survival time of patients with high expression of HK2 was significantly shorter than that of patients with low expression of HK2 (P <0.05). The multivariate Cox proportional hazards regression analysis showed that prognostic stratification, the expression level of HK2, and whether two courses of induction therapy achieved OR were independent factors affecting the prognosis of AML patients (P <0.05).@*CONCLUSIONS@#Compared with allo-HSCT donors, the expression level of HK2 gene is increased in the bone marrow of newly diagnosed AML patients. The prognosis of patients with high expression of HK2 is poor. The expression level of HK2 is an independent factor affecting the prognosis of AML patients.
Subject(s)
Humans , Bone Marrow , Hematopoietic Stem Cell Transplantation/adverse effects , Leukemia, Myeloid, Acute/therapy , Prognosis , Retrospective Studies , Transplantation, Homologous/adverse effectsABSTRACT
The overdiagnosis of prostate cancer (PCa) caused by nonspecific elevation serum prostate-specific antigen (PSA) and the overtreatment of indolent PCa have become a global problem that needs to be solved urgently. We aimed to construct a prediction model and provide a risk stratification system to reduce unnecessary biopsies. In this retrospective study, clinical data of 1807 patients from three Chinese hospitals were used. The final model was built using stepwise logistic regression analysis. The apparent performance of the model was assessed by receiver operating characteristic curves, calibration plots, and decision curve analysis. Finally, a risk stratification system of clinically significant prostate cancer (csPCa) was created, and diagnosis-free survival analyses were performed. Following multivariable screening and evaluation of the diagnostic performances, a final diagnostic model comprised of the PSA density and Prostate Imaging-Reporting and Data System (PI-RADS) score was established. Model validation in the development cohort and two external cohorts showed excellent discrimination and calibration. Finally, we created a risk stratification system using risk thresholds of 0.05 and 0.60 as the cut-off values. The follow-up results indicated that the diagnosis-free survival rate for csPCa at 12 months and 24 months postoperatively was 99.7% and 99.4%, respectively, for patients with a risk threshold below 0.05 after the initial negative prostate biopsy, which was significantly better than patients with higher risk. Our diagnostic model and risk stratification system can achieve a personalized risk calculation of csPCa. It provides a standardized tool for Chinese patients and physicians when considering the necessity of prostate biopsy.
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OBJECTIVE@#To study the clinical manifestations and treatment of intervertebral space infection after percutaneous lumbar radiofrequency ablation of nucleus pulposus.@*METHODS@#A retrospective analysis was performed of 496 patients who underwent percutaneous lumbar disc decompression using low-temperature plasma radiofrequency ablation nucleus pulposus from June 2009 to June 2019. Six patients had lumbar infection, and the infection rate was 1.21%. All patients were male, ranging in age from 20 to 61 years old. Three patients underwent single segment radiofrequency ablation, two patients underwent dual segments ablation;and one patient underwent three segment ablation, totaling 10 intervertebral discs. One patient was complicated with type 2 diabetes before operation. The interval between infection occurrence ranged from 21 to 65 days.@*RESULTS@#All 6 patients were followed up, and the duration ranged from 18 to 40 months, with an average of 24 months. Among them, 2 patients presented with symptoms of low back pain accompanied by fever, and imaging examination showed intervertebral space infection accompanied by abscess. In addition, 4 patients experienced low back pain but no fever, and MRI showed abnormal signals of the infected intervertebral endplate or vertebral body. One patient showed staphylococcus aureus in blood culture, while the remaining 5 patients showed negative bacterial culture. All the patients were treated with antibiotics after diagnosis. Four patients were treated with conservative management to control infection;1 patient was treated with debridement of posterior lumbar infection focus, and 1 patient was treated with debridement of posterior lumbar infection focus combined with interbody fusion and internal fixation.@*CONCLUSION@#The occurrence of intervertebral space infection during lumbar radiofrequency ablation nucleoplasty should be given sufficient attention. Strict aseptic technique, avoiding repeated multi segment puncture, realizing early detection and treatment, and selecting appropriate treatment methods according to the severity of infection is the guarantee of achieving curative effect.
Subject(s)
Humans , Male , Young Adult , Adult , Middle Aged , Female , Low Back Pain , Nucleus Pulposus , Diabetes Mellitus, Type 2 , Retrospective Studies , Spinal PunctureABSTRACT
The study investigated the effect of Buyang Huanwu Decoction(BYHWD) on endogenous biomarkers in the urine of rats with chronic inflammation induced by lipopolysaccharide(LPS) using ultra-high performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry(UPLC-Q-TOF-MS), aiming to elucidate the molecular mechanism underlying the therapeutic effect of BYHWD on chronic inflammation from a metabolomics perspective. Male SD rats were randomly divided into a normal group, a model group, and low-, medium-, and high-dose BYHWD groups(7.5, 15, and 30 g·kg~(-1)). The model group and BYHWD groups received tail intravenous injection of LPS(200 μg·kg~(-1)) on the first day of each week, followed by oral administration of BYHWD once a day for four consecutive weeks. Urine samples were collected at the end of the administration period, and UPLC-Q-TOF-MS was used to analyze the metabolic profiles of the rat urine in each group. Multivariate statistical analysis methods such as principal component analysis(PCA), partial least squares-discriminant analysis(PLS-DA), and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to analyze the effect of BYHWD on endogenous metabolites. One-way ANOVA and variable importance for the projection(VIP) were used to screen for potential biomarkers related to chronic inflammation. The identified biomarkers were subjected to pathway and enrichment analysis using MetaboAnalyst 5.0. A total of 25 potential biomarkers were screened and identified in the rat urine in this experiment. Compared with the normal group, the model group showed significant increases in the levels of 14 substances(P<0.05) and significant decreases in the levels of 11 substances(P<0.05). BYHWD was able to effectively reverse the trend of most endogenous biomarkers. Compared with the model group, BYHWD significantly down-regulated 13 biomarkers(P<0.05) and up-regulated 10 biomarkers(P<0.05). The metabolic products were mainly related to the biosynthesis of pantothenic acid and coenzyme A, tryptophan metabolism, retinol metabolism, and propionate metabolism. BYHWD has therapeutic effect on chronic inflammation induced by LPS, which may be related to its ability to improve the levels of endogenous metabolites, enhance the body's anti-inflammatory and antioxidant capabilities, and restore normal metabolic activity.
Subject(s)
Rats , Male , Animals , Chromatography, High Pressure Liquid/methods , Lipopolysaccharides , Rats, Sprague-Dawley , Metabolomics/methods , Inflammation/drug therapy , Biomarkers/urineABSTRACT
Root rot is a microbial disease that is difficult to control and can result in serious losses in the planting of most Chinese medicinal materials. As high as 87.6% of roots or rhizomes of Chinese medicinal materials are susceptible to root rot, which seriously affects the cultivation development of Chinese medicinal materials. Trichoderma fungi, possessing biological control functions, can induce plants to improve their resistance to microbial diseases, promote plant growth, and effectively reduce the losses caused by various microbial diseases on cultivation. At present, Trichoderma is rarely used in the cultivation of Chinese medicinal materials, so it has great application potential for the prevention and control of root rot diseases in farmed Chinese medicinal materials. Based on the above situation, after comparison and discussion, it is believed that compared with chemical control and physical control, biological control of root rot diseases of Chinese medicinal materials is more efficient and meets the development needs of Chinese medicinal materials ecological planting in China. This paper reviewed the progress in the research and application of Trichoderma in the control of root rot diseases in the root and rhizome of farmed Chinese medicinal materials in the past 10 years and found that most of the current research on the biological control of root rot diseases in Chinese medicinal materials was mostly limited to the verification of the inhibitory effect of Trichoderma strains on the growth of the pathogenic microbes. Studies on the induction effect of Trichoderma on Chinese medicinal materials are not in depth. Studies on the responding mechanisms of most Chinese medicinal materials to Trichoderma are highly absent. Moreover, there are few reports on field experiments, which indicates that there is a long way to go before Trichoderma is widely applied in the farming practice of Chinese medicinal materials. To sum up, this paper aimed to link the present and the future and advocated further relevant research and more experiments on the application of Trichoderma in the farming of Chinese medicinal materials.
Subject(s)
Agriculture , Farms , Plant Diseases/microbiology , Rhizome , TrichodermaABSTRACT
OBJECTIVE@#To develop and validate a three-year risk prediction model for new-onset cardiovascular diseases (CVD) among female patients with breast cancer.@*METHODS@#Based on the data from Inner Mongolia Regional Healthcare Information Platform, female breast cancer patients over 18 years old who had received anti-tumor treatments were included. The candidate predictors were selected by Lasso regression after being included according to the results of the multivariate Fine & Gray model. Cox proportional hazard model, Logistic regression model, Fine & Gray model, random forest model, and XGBoost model were trained on the training set, and the model performance was evaluated on the testing set. The discrimination was evaluated by the area under the curve (AUC) of the receiver operator characteristic curve (ROC), and the calibration was evaluated by the calibration curve.@*RESULTS@#A total of 19 325 breast cancer patients were identified, with an average age of (52.76±10.44) years. The median follow-up was 1.18 [interquartile range (IQR): 2.71] years. In the study, 7 856 patients (40.65%) developed CVD within 3 years after the diagnosis of breast cancer. The final selected variables included age at diagnosis of breast cancer, gross domestic product (GDP) of residence, tumor stage, history of hypertension, ischemic heart disease, and cerebrovascular disease, type of surgery, type of chemotherapy and radiotherapy. In terms of model discrimination, when not considering survival time, the AUC of the XGBoost model was significantly higher than that of the random forest model [0.660 (95%CI: 0.644-0.675) vs. 0.608 (95%CI: 0.591-0.624), P < 0.001] and Logistic regression model [0.609 (95%CI: 0.593-0.625), P < 0.001]. The Logistic regression model and the XGBoost model showed better calibration. When considering survival time, Cox proportional hazard model and Fine & Gray model showed no significant difference for AUC [0.600 (95%CI: 0.584-0.616) vs. 0.615 (95%CI: 0.599-0.631), P=0.188], but Fine & Gray model showed better calibration.@*CONCLUSION@#It is feasible to develop a risk prediction model for new-onset CVD of breast cancer based on regional medical data in China. When not considering survival time, the XGBoost model and the Logistic regression model both showed better performance; Fine & Gray model showed better performance in consideration of survival time.