Objective To investigate the effects of pterostilbene on human colon cancer LoVo cells and study the regulatory mechanism of nuclear factor E2-related factor 2(Nrf2)in the process of pterostilbene acting on LoVo cells.Methods LoVo cells were treated with different concentrations(5,10,20,40,60,80,100 panol/L)of pterostilbene.Cell viability,migration,invasion,and apoptosis were examined by CCK-8,scratch,Tran-swell,and TUNEL assays,respectively.The mitochondrial membrane potential was measured by the mitochon-drial membrane potential assay kit with JC-1.The reactive oxygen species level was measured by 2',7'-dichlo-rofluorescein diacetate.The protein levels of Nrf2,phosphorylated Nrf2,heme oxygenase 1,and apoptotic pro-teins(Bcl2 and Bax)were determined by Western blotting.In addition,cell viability,Nrf2 expression,and ap-optosis rate were determined after co-application of the Nrf2-specific agonist sulforaphane.Results Compared with the control group,40,60,80,100 μmol/L pterostilbene reduced the viability of LoVo cells(P=0.014,P＜0.001,P＜0.001,P＜0.001).Pterostilbene at 5,10,20 μmol/L did not show effects on cell viability but inhibited cell migration(P=0.008,P＜0.001,P＜0.001)and invasion(all P＜0.001).Pterostilbene at 40,60,80 μmol/L increased apoptosis(P=0.014,P＜0.001,P＜0.001),promoted mitochondrial membrane potential depolarization(P=0.026,P＜0.001,P＜0.001)and reactive oxygen species accumula-tion(all P＜0.001),and down-regulated the expression of phosphorylated Nrf2(P=0.030,P＜0.001,P＜0.001),heme oxygenase 1(P=0.015,P＜0.001,P＜0.001),and Bc12(P=0.039,P＜0.001,P＜0.001)in LoVo cells.Pterostilbene at 60,80 μmol/L down-regulated Nrf2 expression(P=0.001,P＜0.001)and up-regulated Bax expression(both P＜0.001).The application of sulforaphane reversed the effects of pterostilbene on cell viability(P＜0.001),apoptosis(P＜0.001),and Nrf2 expression(P=0.022).Conclusion Pterostilbene is a compound that can effectively inhibit colon cancer cells by inhibiting the Nrf2 pathway.

Cutaneous melanoma is a malignant skin cancer with a poor prognosis.However,re-cent advances in immune checkpoint blockade and targeted therapy have significantly improved outcomes in advanced-stage resectable melanoma,which have made neoadjuvant therapy a viable option for melanoma patients.Currently,several relevant clinical trials on neoadjuvant therapy have achieved significant results.This paper reviews the recent advances in neoadjuvant therapy for cutaneous melanoma,focusing on the selection of neoadjuvant therapy,subsequent surgical considerations after neoadjuvant therapy,prognostic indicators,and baseline biomarkers.

Cervical cancer is a common malignant tumor of female reproductive system. The treatment of cervical cancer is based on surgery and radiotherapy (or concurrent chemoradiation). Lower extremity lymphedema (LEL) is a frequent complication after cervical cancer treatment, which significantly affects the quality of life of patients. Both pelvic surgery and radiation for cervical cancer can lead to LEL. The risk factors for LEL are complicated and involving characteristics regarding patient (age, comorbidities, lifestyle, etc.), tumor [International Federation of gynecology and Obstetrics (FIGO) stage, lymph node metastasis, etc.], and treatment (number of resected lymph nodes, removal of circumflex iliac nodes, adjuvant therapy, etc.). Comprehensive measures are proposed to prevent cervical cancer patients from LEL, and further investigations in terms of effectiveness are warranted.

Objective:To investigate the expression of von Hippel-Lindau (VHL), vascular endothelial growth factor (VEGF) and hypoxia inducible factor-1α (HIF-1α) in endolymphatic sac tumor (ELST) and its clinical significance, and to analyze its association with VHL gene mutation.Methods:Twenty-four cases of ELST, which were surgically resected and diagnosed by pathological examination in Beijing Tongren Hospital Affiliated to Capital Medical University, Beijing, China during 2012-2020, were recruited as the ELST group, and 24 cases of otitis media diagnosed in the same hospital were selected as the control group. The expression of VHL, VEGF, and HIF-1α was assessed using EnVision immunohistochemical staining and compared between the ELST and control groups. Sanger sequencing was performed to detect the VHL mutation status in 24 ELSTs. The correlations among VHL, VEGF and HIF-1α expression were analyzed. The associations of VHL, VEGF and HIF-1α expression with age of onset, gender, tumor size, bone invasion and clinical stage in ELST were also analyzed.Results:The expression rate of VHL in the ELST group was significantly lower than that in the control group ( P<0.05), but the expression rates of VEGF and HIF-1α in the ELST group were significantly higher than those in the control group ( P<0.05). VHL expression was inversely correlated with VEGF and HIF-1α expression. The expression of VEGF and HIF-1α was associated with bone invasion and clinical stage ( P<0.05), but the expression of VHL, VEGF and HIF-1α had no significant associations with the age of onset, gender, or tumor size of ELST ( P>0.05). Conclusions:The expression of VHL is decreased while that of VEGF and HIF-1α increased in ELST. Expression of VHL is inversely correlated with that of VEGF and HIF-1α. The expression of VEGF and HIF-1α is correlated with bone invasion and clinical stage. Thus, VEGF and HIF-1α may be therapeutic targets of ELST.

Objective:To compare the therapeutic effects of microdissection tungsten needle and high-frequency electrosurgical generator on open thyroid surgery.Methods:95 patients who underwent open thyroid surgery from Jan. 2017 to Dec. 2017 in the Department of Breast and Thyroid Surgery, Daping Hospital of Army Military Medical University were divided into microdissection tungsten needle group ( n=50) and high-frequency electrosurgical generator group ( n=45) according to different methods. The operation time, intraoperative blood loss, postoperative drainage volume, postoperative complication rate and recurrence and metastasis rate of the two groups were compared. Results:There were no significant differences in operation time (79.3±14.7 vs 73.7±13.9, t=1.914, P=0.059) , intraoperative blood loss (31.8±9.7 vs 30.3±10.6, t=0.702, P=0.484) and postoperative drainage volume (67.3±13.0 vs 71.3±10.8, t=-1.650, P=0.102) between the two groups ( P>0.05) . There were significant differences between the two groups in temporary recurrent laryngeal nerve (RLN) injury (2% vs 17.8%,χ 2=5.518, P=0.023) and temporary hypoparathyroidism (18% vs 44%,χ 2=7.810, P=0.005) , and the results of the microdissection tungsten needle group were better than high-frequency electrosurgical generator group ( P<0.05) . There were no permanent RLN and permanent hypoparathyroidism in the two groups. There were no recurrence and metastasis during the follow-up period. Conclusions:The microdissection tungsten needle is superior to the high-frequency electrosurgical generator in the protection of RLN and parathyroid gland in open thyroid surgery, which is worthy of promotion in clinical application.

Objective:To summarize the experience of diagnosis and treatment of primary thyroid lymphoma (PTL) and improve the level of diagnosis and treatment.Methods:The clinical and pathological data of 19 patients with PTL admitted to the Department of Breast and Thyroid Surgery, Daping Hospital, Army Medical University From Mar. 2000 to Jul. 2019 were retrospectively reviewed.Results:among the 19 PTL patients, 4 were male and 15 were female, with an average age of 69 years (51-88 years) . 15 cases showed rapid enlargement of neck mass, 9 cases with swallowing obstruction, 7 cases with hoarseness and 5 cases with dyspnea. 13 cases were diagnosed by intervention, the other 6 cases were diagnosed by biopsy. There were 1 case of Hodgkin’s lymphoma and 18 cases of non Hodgkin’s lymphoma, including 13 cases of diffuse large B cell lymphoma and 4 cases of mucosa associated lymphoid tissue lymphoma. 12 cases received chemotherapy and 1 case received radiotherapy. The median follow-up period was 28 months (0-88 months) , 5 cases were lost, 6 cases died, 3 cases died of recurrence and spread of lymphoma, 3 cases died of others.Conclusions:PTL is more likely to occur in the elderly women, which is characterized by sudden enlargement of cervical mass and its related compression symptoms. The diagnosis can be confirmed by coarse needle biopsy or surgical intervention. PTL needs comprehensive treatment including surgery, chemotherapy and targeted treatment.

Objective: To evaluate the outcomes of myelodysplastic syndromes (MDS) patients who received HLA-matched sibling donor allogeneic peripheral blood stem cell transplantation (MSD-PBSCT) . Methods: The clinical data of 138 MDS patients received MSD-PBSCT from Sep. 2005 to Dec. 2017 were retrospectively analyzed, and the overall survival (OS) rate, disease-free survival (DFS) rate, relapse rate (RR) , non-relapse mortality (NRM) rate and the related risk factors were explored. Results: ①After a median follow-up of 1 050 (range 4 to 4 988) days, the 3-year OS and DFS rates were (66.6±4.1) % and (63.3±4.1) %, respectively. The 3-year cumulative incidence of RR and NRM rates were (13.9±0.1) % and (22.2±0.1) %, respectively. ②Univariate analysis showed that patients with grade Ⅲ-Ⅳ acute graft-versus-host disease (aGVHD) or hematopoietic cell transplantation comorbidity index (HCT-CI) ≥2 points or patients in very high-risk group of the Revised International Prognostic Scoring System (IPSS-R) had significantly decreased OS[ (42.9±13.2) %vs (72.9±4.2) %, χ²=8.620, P=0.003; (53.3±7.6) %vs (72.6±4.7) %, χ²=6.681, P=0.010; (53.8±6.8) %vs (76.6±6.2) %vs (73.3±7.7) %, χ²=6.337, P=0.042]. For MDS patients with excess blasts-2 (MDS-EB2) and acute myeloid leukemia patients derived from MDS (MDS-AML) , pre-transplant chemotherapy or hypomethylating agents (HMA) therapy could not improve the OS rate[ (60.4±7.8) %vs (59.2±9.6) %, χ²=0.042, P=0.838]. ③Multivariate analysis indicated that the HCT-CI was an independent risk factor for OS and DFS (P=0.012, HR=2.108, 95%CI 1.174-3.785; P=0.008, HR=2.128, 95%CI 1.219-3.712) . Conclusions HCT-CI was better than the IPSS-R in predicting the outcomes after transplantation. The occurrence of grade Ⅲ-Ⅳ aGVHD is a poor prognostic factor for OS. For patients of MDS-EB2 and MDS-AML, immediate transplantation was recommended instead of receiving pre-transplant chemotherapy or HMA therapy.

Objective:To explore the clinical characteristics, related factors, and prognostic effect of patients with T cell large granular lymphocytosis following allo-HSCT.Methods:Consecutive patients with T-LGL following allo-HSCT who visited our center from June 2013 to February 2020 were studied retrospectively. We compared patients undergoing allo-HSCT during this period. The clinical characteristics, related factors, cumulative incidence of patients with T-LGL and rates of overall survival (OS) , disease free survival (DFS) , relapse, and non-relapse mortality (NRM) were analyzed.Results:Total 359 patients were enrolled, including 17 with T-LGL and 342 without T-LGL following allo-HSCT. The median follow-up duration was 38 (3-92) month. The cumulative incidence at 1-, 2- and 3-years of T-LGL was 3.64% (95% CI 1.09%-6.19%) , 4.50% (95% CI 1.36%-7.64%) , and 4.84% (95% CI 1.10%-8.76%) , respectively. CMV reactivation ( P=0.013) , EB viremia ( P=0.034) , and aGVHD ( P=0.027) were associated with the development of T-LGL following allo-HSCT. Multivariate analysis showed that benign hematologic diseases[ P=0.027, OR=3.36 (95% CI 1.15-9.89) ] and haploidentical hematopoietic stem cell transplantation[ P=0.030, OR=4.67 (95% CI 1.16-18.75) ], unrelated donor transplantation[ P=0.041, OR=5.49 (95% CI 1.10-28.16) ] were independent predictive factors of T-LGL following allo-HSCT. There was a significant difference in the 3-year OS (100.0% vs. 78.6%, P=0.04) , DFS (100.0% vs. 70.0%, P=0.01) , and NRM (0 vs. 12.6%, P=0.02) between the 2 cohorts. Subgroup analysis showed that malignant diseases recipients who developed T-LGL had better outcomes after allo-HSCT, and there was a significant difference in the NRM ( P=0.042) , DFS ( P=0.013) , and cumulative relapse rate ( P=0.028) between the 2 cohorts. In contrast, the appearance of T-LGL after allo-HSCT in patients with benign diseases had no significant effect on the prognosis. Conclusions:T-LGL was a durable and clinically benign phenomenon occurring in allo-HSCT recipients with malignant diseases. Factors associated with immune reconstitution and T-cell regulatory mechanisms might be major predictors of T-LGL following allo-HSCT.

Objective:To investigate the distribution of pathogens and the antibiotic resistance profile of bloodstream infections in adult patients with hematological diseases in the period 2014-2018 to provide evidence for the rational use of antibiotics.Methods:We retrospectively analyzed the bloodstream infections in patients with hematological diseases from January 2014 to December 2018 at the institute of Hematology & Blood Diseases Hospital; this included an assessment of the clinical characteristics, distribution of pathogens, and antibiotic resistance data.Results:There were 1935 episodes of BSIs in the 1478 patients who were studied; among these, 1700 episodes occurred in the neutropenic phase. The 7-day and 30-day all-cause mortality rates were 5.5% and 8.2%, respectively. Bloodstream infection was usually accompanied by respiratory tract, perianal zone mucositis, and digestive tract symptoms; the respective proportions were 12.4%, 12.3%, and 9.1%, respectively. Total 2025 strains were isolated; 1551 (76.6%) of the pathogens were gram-negative bacteria, mainly Escherichia coli, Klebsiella pneumonia, and Pseudomonas aeruginosa; 423 (20.9%) were gram-positive bacteria, mainly Staphylococcus spp. and Streptococcus spp. Viridans; 51 (2.5%) were fungi, mainly Candida tropicalis. The resistance rates of Enterobateriaceae to piperacillin/tazobactam, carbapenems, amikacin were <10%. The resistance rates of K. pneumoniae to cefepime, piperacillin/tazobactam and meropenem increased annually. The resistance rates of Pseudomonas aeruginosa to piperacillin/tazobactam, quinolones, Aminoglycosides were <5% even when compared to carbapenems. Eleven stains of methicillin-resistant S. aureus and 1 stain of vancomycin-resistant Enterococcus faecium were detected.Conclusion:The pathogens of bloodstream infection in adult patients with hematological diseases are widely distributed. The resistance rates of different strains vary; the rates in some species had a tendency to increase. Antibiotics should be selected rationally as per the distribution of pathogens and resistance to antibiotics in different patient groups.

Objective:To explore the clinical efficacy of different modes of continuous negative pressure wound therapy (NPWT) on venous ulcer wounds of lower limbs, and to analyze the influencing factors.Methods:From January 2018 to December 2019, 53 patients with venous ulcer of lower limbs who met the inclusion criteria and hospitalized in the Affiliated Hospital of Jiangnan University were recruited in this prospective randomized controlled study. According to the random number table, the patients were divided into single negative pressure therapy (SNPT) group (19 patients, 11 males and 8 females), cyclic alternating negative pressure therapy (CANPT) group (17 patients, 12 males and 5 females), and routine dressing change (RDC) group (17 patients, 10 males and 7 females), aged (47±11), (49±10), and (47±10) years respectively. After admission, patients in SNPT group were given continuous NPWT with the single negative pressure setting at -13.3 kPa, patients in CANPT group were also given continuous NPWT but with the cyclic alternating negative pressure setting from -16.0 to -10.7 kPa, while patients in RDC group were given dressing change with vaseline gauze soaked with iodophor. The wound healing rate was calculated on treatment day 7 and 14. Transcutaneous oxygen pressure (TcPO 2) around the wound was detected by TcPO 2 meter before treatment and on treatment day 7 and 14. The wound exudate/drainage fluid was collected on treatment day 1, 4, 7, 10, and 14, with the pH value measured using a pH meter, and the volume of exudate/drainage fluid recorded. Before treatment and on treatment day 7 and 14, venous blood was collected to detect the serum levels of interleukin 1β (IL-1β), IL-6, tumor necrosis factor α(TNF-α), transforming growth factor-β 1 (TGF-β 1), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Before treatment and on treatment day 7 and 14, wound exudates were collected for bacterial culture, and Visual Analogue Scale and Hamilton Anxiety Scale were used to evaluate the degree of wound pain and anxiety of patients respectively. The length of hospital stay and the total treatment cost were counted. Analysis of variance for repeated measurement, one-way analysis of variance, least significant difference test, Kruskal Wallis H test, Mann Whitney U test, chi-square test, Fisher′s exact probability method test, and Bonferroni correction were used to analyze the data. According to the wound healing rate on treatment day 14, the efficiency of patients were divided into two grades of significant healing with wound healing rate≥70% and non significant healing with wound healing rate<70%. According to the two categories of wound healing rate as dependent variables, the levels of TcPO 2, IL-1β, IL-6, TNF-α, TGF-β 1, VEGF, bFGF levels and bacterial detection, wound pain and anxiety before treatment, wound exudate/drainage fluid volume and pH value on treatment day 1 were taken as covariates, and binary classification multifactor logistic regression analysis was used to analyze the risk factors of significant wound healing. Results:(1) On treatment day 7, the wound healing rate of patients in SNPT group was (33±10) %, which was significantly higher than (24±9) % of RDC group ( P<0.05). On treatment day 14, the wound healing rates of patients in SNPT group and CANPT group were (71±15)% and (66±18)%, respectively, which were significantly higher than (45±19)% of RDC group ( P<0.01). (2) Compared with those of RDC group, the TcPO 2 value around the wound of patients was significantly increased in SNPT group on treatment day 14 and in CANPT group on treatment day 7 and 14 ( P<0.05 or P<0.01), the pH value of wound drainage fluid of patients was significantly decreased in SNPT group on treatment day 10 and 14 and in CANPT group on treatment day 7 and 14 ( P<0.05), the volume of wound drainage fluid of patients was significantly reduced in SNPT group on treatment day 10 and 14 and in CANPT group on treatment day 7, 10, and 14 ( Z=-4.060, -4.954, -2.413, -4.085, -4.756, P<0.05 or P<0.01), the serum levels of IL-1β, IL-6, and TNF-α of patients were significantly decreased in SNPT group and CANPT group on treatment day 7 and 14 ( P<0.01), the serum level of TGF-β 1 of patients was significantly increased in CANPT group on treatment day 14 ( P<0.05), the serum levels of VEGF and bFGF were significantly increased in SNPT group and CANPT group on treatment day 14 ( P<0.01), the bacteria detection proportion of wound exudate, wound pain, and anxiety scores of patients were significantly decreased in SNPT group and CANPT group on treatment day 7 and 14 ( P<0.01). Compared between the negative pressure therapy two groups, except the wound pain score of patients in CANPT group was significantly lower than that in SNPT group ( P<0.01) on treatment day 7, the other indicators mentioned above were similar. (3) The length of hospital stay of patients in SNPT group was similar to that in CANPT group ( P>0.05), which were significantly shorter than the time in RDC group ( P<0.01). The total treatment cost of patients among the three groups was similar ( F=1.766, P>0.05). (4) Before treatment, the serum levels of TNF-α and bFGF, TcPO 2 around the wound, and the degree of wound pain were risk factors for significant wound healing (odds ratio=1.109, 0.950, 1.140, 2.169, 95% confidence interval=1.012-1.217, 0.912-0.988, 1.008-1.290, 1.288-3.651, P<0.05 or P<0.01). Conclusions:Clinical application of continuous NPWT under single negative pressure mode and cyclic alternating negative pressure mode has a positive effect on improving the wound base and healing rate of venous ulcer of lower limbs. But cyclic alternating negative pressure mode is significantly more effective than single negative pressure mode in improving TcPO 2 around the wound, reducing wound pH value, reducing exudate volume and relieving pain. The serum levels of TNF-α and bFGF, TcPO 2 around the wound and the degree of wound pain were the risk factors that affect the wound healing significantly.