OBJECTIVE: To analyze the Epstein-Barr virus (EBV) load in different lymphocyte subsets, as well as clinical characteristics and outcomes in patients with hematologic malignancies experiencing EBV reactivation. METHODS: Peripheral blood samples from patients were collected. B, T, and NK cells were isolated sorting with magnetic beads by flow cytometry. The EBV load in each subset was quantitated by real-time quantitative polymerase chain reaction (RT-qPCR). Clinical data were colleted from electronic medical records. Survival status was followed up through outpatient visits and telephone calls. Statistical analyses were performed using SPSS 25.0. RESULTS: A total of 39 patients with hematologic malignancies were included, among whom 35 patients had undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). The median time to EBV reactivation was 4.8 months (range: 1.7-57.1 months) after allo-HSCT. EBV was detected in B, T, and NK cells in 20 patients, in B and T cells in 11 patients, and only in B cells in 4 patients. In the 35 patients, the median EBV load in B cells was 2.19×10⁴ copies/ml, significantly higher than that in T cells (4.00×10³ copies/ml, P <0.01) and NK cells (2.85×10² copies/ml, P <0.01). Rituximab (RTX) was administered for 32 patients, resulting in EBV negativity in 32 patients with a median time of 8 days (range: 2-39 days). Post-treatment analysis of 13 patients showed EBV were all negative in B, T, and NK cells. In the four non-transplant patients, the median time to EBV reactivation was 35 days (range: 1-328 days) after diagnosis of the primary disease. EBV was detected in one or two subsets of B, T, or NK cells, but not simultaneously in all three subsets. These patients received a combination chemotherapy targeting at the primary disease, with 3 patients achieving EBV negativity, and the median time to be negative was 40 days (range: 13-75 days). CONCLUSION In hematologic malignancy patients after allo-HSCT, EBV reactivation commonly involves B, T, and NK cells, with a significantly higher viral load in B cells compared to T and NK cells. Rituximab is effective for EBV clearance. In non-transplant patients, EBV reactivation is restricted to one or two lymphocyte subsets, and clearance is slower, highlighting the need for prompt anti-tumor therapy.
Humans ; Hematologic Neoplasms/virology* ; Herpesvirus 4, Human/physiology* ; Epstein-Barr Virus Infections ; Hematopoietic Stem Cell Transplantation ; Virus Activation ; Lymphocyte Subsets/virology* ; Flow Cytometry ; Killer Cells, Natural/virology* ; Male ; Female ; B-Lymphocytes/virology* ; Viral Load ; Adult ; T-Lymphocytes/virology* ; Middle Aged

Long non-coding RNA SLC25A25-AS1 has a tumor inhibition effect in the development of colorectal cancer. However‚ the mechanism of SLC25A25-AS1 in cervical cancer needs further study. We studied the abnormal expression of SLC25A25-AS1 in the serum of the patients with cervical cancer and the patients with cervical intraepithelial neoplasia (CIN) and explored the mechanism of SLC25A25-AS1 in the development of cervical cancer. The expression levels of SLC25A25-AS1 in the serum of normal controls‚ patients with cervical cancer‚ and patients with CIN were detected by RT-qPCR. The important role of SLC25A25-AS1 in HeLa cells was analyzed in vitro and in vivo experiments. Compared with the normal group‚ the expression level of serum SLC25A25-AS1 was decreased in patients with cervical cancer. In vitro‚ overexpression of SLC25A25-AS1 inhibited cell proliferation‚ migration‚ and invasion of HeLa cells. Tumor formation in nude mice assay showed that the subcutaneous tumor weight and volume of nude mice injected with SLC25A25-AS1-overexpressed HeLa cells were significantly smaller than that of nude mice injected with control cells (P<0. 05). SLC25A25-AS1 may play an important role in the development of cervical cancer and may serve as a new therapeutic target for cervical cancer.

Objectiveezrin gene is overexpressed in pancreatic cancer, and its upstream sequence plays an important role in gene expression. This study intends to knock out ezrin transcriptional regulatory region and identify its gRNA target sites for gene editing in pancreatic cancer cells.MethodsThe reporter gene expression vectors carrying the upstream segment of ezrin gene were transiently transfected into Panc-1 cells. The ezrin transcriptional regulatory regions were identified by double luciferase reporter gene detection system. Then, the online software was utilized to predict the gRNA target sites located at the upstream and downstream of ezrin transcriptional regulatory region. Two recombinant plasmids pX459-sgRNA-L and pX458-sgRNA-R contained these two sequences were constructed for gene editing. Moreover, in order to identify the targeted knockout of ezrin transcriptional regulatory region, the recombinant plasmids were co-transfected into Panc-1 cells, and the genome DNA contained gRNA target sites were amplified, subcloned and sequenced. Finally, Panc-1 cells transfected with recombinant plasmids were preliminary sorted using puromycin treatment. The cell proliferation was detected by water-soluble tetrazolium salt method.ResultsLuciferase data showed that ezrin gene fragment -1297/-1186 enhanced the transcriptional activity of SV40 promoter and ezrin promoter in Panc-1 cells. Subclonal sequencing data revealed that the recombinant plasmids carrying the gRNA target sequence of ezrin transcriptional regulatory region were co-transfected into Panc-1 cells could trigger the genomic DNA fragments, which located between gRNA-L and gRNA-R target sites. Cell proliferation assay showed that the proliferation was significantly inhibited after transfection.ConclusionThe targeted knockout of ezrin transcriptional regulatory region was achieved and the inhibition of Panc-1 cell proliferation may be related to this knockout.

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

5-HT as an important neurotransmitter which takes part in the development of many diseases, including bronchial asthma,schizophrenia and bone metabolism as reported in literatures in recent years. Central 5-HT can inhibit sympathetic excitations and promote bone formation through Tph2. Lrp5 can reduce the level of peripheral 5-HT and act on Tph1 to promote bone formation. Peripheral 5-HT blocks the association between transcription factor FOXO1 and CREB and inhibits bone formation. Peripheral 5-HT can also promote IL-6 expression and induce bone reabsorption. LP533401 as a Tph1 inhibitor could effectively reduce the level of peripheral 5-HT and induce bone formation as reported. In this paper, we try to summarize the effect of 5-HT on bone metabolism and its mechanism, and further using 5-HT to regulate bone quantity effectively.

Objective To compare the effects of fixations with dynamic hip screw (DHS),percutaneous compression plate (PCCP) and proximal femoral nail anti-rotation (PFNA) for treatment of intertrochanteric femoral fractures with paries medialis defect.Methods We reviewed the 82 patients with femoral intertrochanteric fracture and paries medialis defect who had been treated at our department from January 2011 to July 2016.They were 42 men and 40 women,aged from 27 to 91 years (average,73.0 years).According to the AO classification,72 cases belonged to type 31-A2.2,10 to type 31-A2.3.Of them,9 cases were treated with DHS,17 cases with PCCP and 56 cases with PFNA-1].The 3 groups were compared in terms of intraoperative blood loss,blood infusion,fluid infusion,operation duration,time for fracture union,postoperative complications and Functional Recovery Score (FRS) of the hip 12 months after operation.Results The fluid infusion [1,100 (850,1,100) mL] and intraoperative blood loss [60 (5,100) mL] in the PCCP group were significantly less than in the PFNA group [1,100 (1,000,1,700) mL and 150 (50,300) mL] and the operation duration (91.4 ± 29.2 min) in the former was significantly shorter than in the latter [121 (85,185) min] (P ＜ 0.05).No significant difference was found between the 3 groups in blood infusion (P ＞ 0.05).Of the patients,57 (8 DHS,12 PCCP and 37 PFNA ones) were followed up for an average of 47 months (from 15 to 85 months).There were no statistically significant differences between the 3 groups in time for fracture union,complications,or average FRS score of the hip 12 months after operation (P ＞ 0.05).Conclusions For unstable intertrochanteric fractures with paries medialis defect,it is not clear that intramedullary nails are superior to extramedullary fixation.Intramedullary nails like PFNA may be suggested for patients with better preoperative conditions while extramedullary fixation like PCCP suggested for those with poor general conditions.

Objective The relationship between osteoblast autophagy induced by wear particles and secretion of inflammatory cytokines has not been illuminated.The purpose of this study was to investigate the effect of wear particles on the secretion of TNF -α and IL-6 by autophagy of osteoblasts in aseptic loosening. Methods The mouse MC3T3-E1 osteoblasts in logarithmic growth phase were divided into 5 groups:control group(in α-MEM medium),CoCrMo particle group(100 μg/mL CoCrMo particles was added in α-MEM medium),3-MA group(10 mmol/L autophagy inhibitor 3-MA prestimulated osteoblasts in α-MEM medium,3h later 100 μg/mL CoCrMo particles were added),the expression of autophagy marker protein LC-3 in osteoblasts was detected by Western blotting, and the levels of TNF-αand IL-6 were detected by ELISA. Results Compared with the control group,the expression level of auto-phagy marker protein LC-3 was significantly increased in CoCrMo particles group(P<0.05).Compared with CoCrMo particles group,the expression level of LC-3 in 3-MA group was significantly decreased(P<0.05).Compared with control group TNF-α[(0.95± 0.00)pg/mL]and IL-6[(4.67±0.23)pg/mL], CoCrMo particles group TNF-α[(10.35±3.63)pg/mL]and IL-6[(14.27±1.07)pg/mL]secretion level was significantly increased(P<0.05),compared with CoCrMo particles group,the effects of 10 mmol/L 3-MA group to TNF-α[(13.13±5.08)(14.71±5.46)pg/mL]and IL-6[(15.31±0.88),(16.75±3.87)pg/mL]secretion were not significant, while 10 mmol/L 3-MA group TNF-α[The secretion levels of(302.61±45.63)pg/mL]and IL-6[(216.67±27.71)pg/mL]in-creased significantly(P<0.01). Conclusion The osteoblast autophagy induced by CoCrMo particles can inhibit the secretion of in -flammatory cytokines TNF-αand IL-6 in osteoblasts.

OBJECTIVETo investigate the short-term clinical outcome of unicompartmental knee arthroplasty for the treatment of spontaneous osteonecrosis of the knee.

METHODSFrom September 2013 to April 2014,5 patients with spontaneous osteonecrosis of the knee underwent unicompartmental knee arthroplasty, included 3 males and 2 females, aged from 65 to 80 years old with an average of 74 years. The courses of disease was from 1 to 6 years with the mean of 3 years. According to the radiographic staging criteria of Koshino, 1 case was stage II, 2 cases were stage III, 2 cases were stage IV. Clinical effects were assessed by VAS score, HSS score, and knee range of motion, tibiofemoral angle before and after operation.

RESULTSAll the patients were followed up from 6 to 7 months with an average of 6.4 months. All incisions obtained primary healing, and there were no complications such as infection, thrombosis, fracture of lower limbs. All 5 patients' pain relieved and their knee function improved significantly after operation, but knee range of motion had no obviously improved. Postoperative HSS scores, VAS scores, tibiofemoral angle were significantly improved than that of preoperative.

CONCLUSIONThe short-term effect of unicompartmental knee arthroplasty in treating spontaneous osteonecrosis of the knee is satisfactory.

Aged ; Aged, 80 and over ; Arthroplasty, Replacement, Knee ; methods ; Female ; Humans ; Joint Diseases ; physiopathology ; surgery ; Knee Joint ; Male ; Osteonecrosis ; physiopathology ; surgery ; Range of Motion, Articular

Introduction:Right-sided colon cancer (RSCC) and left-sided colorectal cancer (LSCRC) differ with respect to their biology and genomic patterns. This study aimed to examine whether the primary tumor location is associated with the response to cetuximab in patients with metastatic colorectal cancer (mCRC). Methods:Patients with mCRC treated with cetuximab and standard chemotherapy as first-or second-line treatments were compared with randomly chosen patients who were treated with chemotherapy alone between 2005 and 2013. The main outcome measures were the overal response rate (ORR), progression-free survival (PFS), and overal survival (OS). The differences in the outcome were analyzed by using the chi-squared test, Student’s t test, and Kaplan-Meier method. Results:The treatment results of 206 patients with mCRC treated with cetuximab and standard chemotherapy as first-or second-line treatments were compared with those of 210 patients who were treated with chemotherapy alone. As a first-line treatment, cetuximab with chemotherapy was associated with a significantly higher ORR (49.4%vs. 28.6%, P=0.005) as well as longer PFS (9.1 vs. 6.2 months, P=0.002) and OS (28.9 vs. 20.1 months, P=0.036) than chemotherapy alone in patients with LSCRC. However, cetuximab neither improved the ORR (36.4%vs. 26.2%, P=0.349) nor prolonged PFS (5.6 vs. 5.7 months, P=0.904) or OS (25.1 vs. 19.8 months, P=0.553) in patients with RSCC. As a second-line treatment, cetuximab exhibited a tendency to improve the ORR (23.5%vs. 10.2%, P=0.087) and prolong PFS (4.9 vs. 3.5 months, P=0.064), and it significantly prolonged OS (17.1 vs. 12.4 months, P=0.047) compared with chemotherapy alone in the patients with LSCRC. In contrast, as a second-line treatment, cetuximab neither improved the ORR (7.1%vs. 11.4%, P=0.698) nor prolonged PFS (3.3 vs. 4.2 months, P=0.761) or OS (13.4 vs. 13.0 months, P=0.652) in patients with RSCC. Conclusions:The addition of cetuximab to chemotherapy in both first-and second-line treatments of mCRC may only benefit patients with primary LSCRC.