Owing to incurable castration-resistant prostate cancer (CRPC) ultimately developing after treating with androgen deprivation therapy (ADT), it is vital to devise new therapeutic strategies to treat CRPC. Treatments that target programmed cell death protein 1 (PD-1) and programmed death ligand-1 (PD-L1) have been approved for human cancers with clinical benefit. However, many patients, especially prostate cancer, fail to respond to anti-PD-1/PD-L1 treatment, so it is an urgent need to seek a support strategy for improving the traditional PD-1/PD-L1 targeting immunotherapy. In the present study, analyzing the data from our prostate cancer tissue microarray, we found that PD-L1 expression was positively correlated with the expression of heterogeneous nuclear ribonucleoprotein L (HnRNP L). Hence, we further investigated the potential role of HnRNP L on the PD-L1 expression, the sensitivity of cancer cells to T-cell killing and the synergistic effect with anti-PD-1 therapy in CRPC. Indeed, HnRNP L knockdown effectively decreased PD-L1 expression and recovered the sensitivity of cancer cells to T-cell killing in vitro and in vivo, on the contrary, HnRNP L overexpression led to the opposite effect in CRPC cells. In addition, consistent with the previous study, we revealed that ferroptosis played a critical role in T-cell-induced cancer cell death, and HnRNP L promoted the cancer immune escape partly through targeting YY1/PD-L1 axis and inhibiting ferroptosis in CRPC cells. Furthermore, HnRNP L knockdown enhanced antitumor immunity by recruiting infiltrating CD8⁺ T cells and synergized with anti-PD-1 therapy in CRPC tumors. This study provided biological evidence that HnRNP L knockdown might be a novel therapeutic agent in PD-L1/PD-1 blockade strategy that enhanced anti-tumor immune response in CRPC.

Membrane-disruptive peptides/peptidomimetics (MDPs) are antimicrobials or anticarcinogens that present a general killing mechanism through the physical disruption of cell membranes, in contrast to conventional chemotherapeutic drugs, which act on precise targets such as DNA or specific enzymes. Owing to their rapid action, broad-spectrum activity, and mechanisms of action that potentially hinder the development of resistance, MDPs have been increasingly considered as future therapeutics in the drug-resistant era. Recently, growing experimental evidence has demonstrated that MDPs can also be utilized as adjuvants to enhance the therapeutic effects of other agents. In this review, we evaluate the literature around the broad-spectrum antimicrobial properties and anticancer activity of MDPs, and summarize the current development and mechanisms of MDPs alone or in combination with other agents. Notably, this review highlights recent advances in the design of various MDP-based drug delivery systems that can improve the therapeutic effect of MDPs, minimize side effects, and promote the co-delivery of multiple chemotherapeutics, for more efficient antimicrobial and anticancer therapy.

Pancreatic duct stone is a sequel of chronic pancreatitis and may be found in the main ducts,side branches or parenchyma.These stones obstruct the pancreatic ducts and produce ductal hypertension,which leads to pain,the cardinal feature of CP.Surgical operation has been the preferred treatment of pancreatic duct stones in many domestic and external pancreatic medical centers.Lithotomy by longitudinal pancreatic duct incision and Roux-en-Y anastomosis of pancreatic duct to jejunum is the main and effective surgical procedure,while micro-surgery was also rational for the treatment of pancreatic duct stones.However,further studies with a larger sample size and longer follow-up duration are needed to improve the surgical technique and verify our initial results.

Objective To investigate the relationship between serum free fatty acids (FFA) and insulin resistance (IR) in patients with type 2 diabetes mellitus (T2DM).Methods Totally 106 T2DM patients were selected as observation group,and 106 healthy people were selected as control group.Body mass index (BMI),FPG,FFA,HbAlc,TG,TC and HOMA-IR were compared between two groups.According to the blood glucose level,the T2DM patients were divided into good control group (n =56) and bad control group (n =50),and the FFA and HOMA-IR were compared two groups.Correlation between serum FFA and HOMA-IR in patients with T2DM was analyzed.Results In the observation group,BMI,FPG,FFA,HbA1 C,TC,TG and HOMA-IR were significantly higher than the control group (P ＜ 0.05).FFA and HOMA-IR in bad control group were significantly higher than the good control group (P ＜ 0.05).Correlation analysis showed that serum FFA was positively correlated with HOMA-IR level in T2DM patients (r =0.621,P ＜ 0.05).Conclusion Serum free fatty acids level is closely related to insulin resistance in patients with T2DM,which can reflect the blood glucose control level.

Objective To investigate the relationship between serum free fatty acids (FFA) and insulin resistance (IR) in patients with type 2 diabetes mellitus (T2DM).Methods Totally 106 T2DM patients were selected as observation group,and 106 healthy people were selected as control group.Body mass index (BMI),FPG,FFA,HbAlc,TG,TC and HOMA-IR were compared between two groups.According to the blood glucose level,the T2DM patients were divided into good control group (n =56) and bad control group (n =50),and the FFA and HOMA-IR were compared two groups.Correlation between serum FFA and HOMA-IR in patients with T2DM was analyzed.Results In the observation group,BMI,FPG,FFA,HbA1 C,TC,TG and HOMA-IR were significantly higher than the control group (P ＜ 0.05).FFA and HOMA-IR in bad control group were significantly higher than the good control group (P ＜ 0.05).Correlation analysis showed that serum FFA was positively correlated with HOMA-IR level in T2DM patients (r =0.621,P ＜ 0.05).Conclusion Serum free fatty acids level is closely related to insulin resistance in patients with T2DM,which can reflect the blood glucose control level.

Objective To observe the effect of Huangxiong Kangshuan capsule on serum high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6) levels in patients with acute cerebral infarction. Methods Ninety-two patients with acute cerebral infarction admitted to the First Affiliated Hospital of Anhui University of Traditional Chinese Medicinefrom July 2013 to December 2016 were enrolled, and they were divided into an observation group (47 cases) and a control group (45 cases) by random number table. The control group was given conventional treatment of ischemic cerebrovascular disease, while the observation group was additionally treated by Huangxiong Kangshuan capsule orally taken, once 3 tablets, 3 times a day, on the basis of routine treatment; the duration of treatment was 2 weeks in both groups. After 2 weeks of treatment, the clinical effects of the two groups and the changes of serum hs-CRP and IL-6 levels were observed.Results After treatment, the levels of serum hs-CRP and IL-6 were decreased significantly compared with those before treatment in the two groups [observation group: hs-CRP (mg/L) was 6.18±2.17 vs. 14.11±3.01, IL-6 (ng/L): 28.10±11.47 vs. 120.83±24.51; control group: hs-CRP (mg/L) was 8.89±2.46 vs. 13.97±2.69, IL-6 (ng/L) was 49.48±16.43 vs. 115.25±24.05], and the degree of decline in the observation group was more significant than that in the control group [hs-CRP (mg/L): 6.18±2.17 vs. 8.89±2.46, IL-6 (ng/L): 28.10±11.47 vs. 49.48±16.43, bothP < 0.01]; the total effective rate of the observation group was significantly higher than that of the control group [87.2% (41/47) vs. 71.1% (32/45),P < 0.05]. Conclusion Huangxiong Kangshuan capsule can decrease the serum hs-CRP and IL-6 levels in patients with acute cerebral infarction, and has a role in brain protection and nerve function defect improvement.

Objective To assess the diagnostic value of IMA,NLR,hs-CRP and CK-MB individually and the combined detec-tion for early acute myocardial infarction using ROC curve and Logistic regression.Methods To detect levels of IMA,NLR, hs-CRP,CK-MB and cTnI in serum or whole blood of AMI patients that had chest pain within 3 hours or between 3 and 6 hours,compared with 60 healthy people from Physical Examination Center.Applied Logistic regression,plotted ROC curve and calculated the area under ROC curve (AUC)to assess the diagnostic value of each index.Results The serum IMA,hs-CRP,CK-MB and cTnI or whole blood NLR levels of AMI patients with 3 hours were remarkably higher than normal con-trol,showing significant statistical difference (P<0.01)(AMI group:mean values of IMA,NLR,hs-CRP,CK-MB and cTnI were 96.04 U/L,3.77,13.39 mg/L,43.26 U/L and 0.063 ng/ml;normal control group:mean values of IMA,NLR,hs-CRP,CK-MB and cTnI were 78.10 U/L,2.02,3.12 mg/L,19.37 U/L and 0.040 ng/ml.The serum IMA,NLR,hs-CRP, CK-MB and cTnI levels of AMI patients in the group between 3~6 hours were higher than in the group within 3 hours (P<0.05).The AUC of combined detection of IMA,NLR,hs-CRP and CK-MB for early AMI was 0.98,higher than solo de-tection of IMA,NLR,hs-CRP and CK-MB,which were 0.89,0.83,0.79 and 0.85 respectively.Meanwhile,the AUC of com-bined detection for four markers also surpassed that of cTnI alone that was recognized as a classic serological marker to diag-nose AMI (AUC=0.78).Conclusion The combined detection of IMA,NLR,hs-CRP and CK-MB is superior to a single in-dex detection,which can significantly improve diagnostic efficiency for early AMI.

OBJECTIVE To investigate the effects of recombinant human epidermal growth factor (rhEGF) on wound healing of chronic sinusitis patients after functional endoscopic sinus surgery. METHODS A total of 110 patients with chronic sinusitis underwent functional endoscopic sinus surgery with both sides of their nose. The right side of their nasal cavity (control group) treated by nasal irrigation and steroid nasal spray, the left side of their nasal cavity (study group) treated by nasal irrigation and the nasal spray of steroid hormones and rhEGF. Surgical effect was evaluated under nasal endoscope at 2, 4, 12 and 24 weeks after surgery, while subjective symptom was evaluated depending on visual analogue scale (VAS). Both the score of endoscopic examination and VAS, also the rates of epithelization of the two groups were compared. RESULTS The score of endoscopic examination of the study group at 2 weeks after surgery was better than that of the control group, which had statistical significance, while the score of VAS had no statistical difference. The score of endoscopic examination and VAS, the rate of epithelization in study group at 4 and 12 weeks after surgery were better than those in control group, and the difference was statistically significant, but they were no statistical difference at 24 weeks after surgery. CONCLUSION The using of rhEGF nasal spray on chronic sinusitis patients with functional endoscopic sinus surgery can shorten the time of epithelization, improve the situation of nasal mucosa and patients' subjective symptoms, it is worthy of clinical application.

Objective To study changes in expression of claudin-11 and proteins related to mitogen-activated protein kinase (MAPK) signaling pathways, as well as the ultrastructure of the blood testis barrier(BTB), in male ICR mice exposed to decabromodiphenyl ether (BDE-209). Methods Fifty-two mice, 4 weeks of age, weighing 15-21 g, were provided with adaptive feeding for 1 week. Mice were randomly divided into 4 groups, named control, low-dose, medium-dose and high-dose groups. The treated groups received BDE-209, by intragastric gavage, at doses, respectively, of 100, 300 and 500 mg/kg. Mice were sacrificed after 6 weeks and organs harvested on ice, weighed and stored at-80 °C. The ultrastructure of testicular tissues was examined by electron microscopy. Western blotting was used to detect proteins related to the MAPK pathway, including p38 mitogen activated protein kinase (p38), phosphorylated p38 (p-p38), extracellular regulated protein kinase 1/2 (ERK1/2) , phosphorylated ERK1/2 (p-ERK1/2) , c-jun N-terminal kinase (JNK), phosphorylated JNK (p-JNK) and the BTB tight junction protein claudin-11. Analyze the difference between each groups. Results At sacrifice, the body weights in each treated group were compared with those in the control group weighing (41.14 ± 0.60) g. Compared with controls, body weights were significantly different (P<0.05) in the middle dose, at (39.97 ± 0.66) g and high dose, at (39.98± 0.55) g in control group. The coefficients of the testis were significantly lower (P<0.05) in each treated group than in controls, with values of (0.37±0.0)%, (0.31±0.05)% and (0.31±0.04)% for low- dose, medium-dose and high-dose groups, respectively. The epidymus coefficient values were also significantly lower than controls (P<0.05), with values of (0.16±0.06)%, (0.11±0.05)% and (0.07±0.03)%, respectively in the same three dose groups. Electron microscopy ultrastructure showed that, compared with the control group, the testes in the middle and high dose groups had closely connected fractures, cell edema and more vacuoles. Compared with in the control group, levels of p-p38 and p-JNK in testicular tissue were significantly increased (P<0.05). In the control group and in low-, medium- and high-dose groups, the p-p38/p38 ratios were 1.35±0.13, 3.46±0.10, 5.71±0.26 and 4.79±0.21, respectively. The corresponding p-JNK/JNK ratios were 2.07±0.0, 4.77±0.18, 3.63±0.06 and 4.85±0.15. Claudin-11 levels were significantly lower (P<0.05) than control values in each dosed group. The corresponding values in control, low-dose, medium-dose and high-dose groups were 8.33±0.36, 2.06±0.27, 3.37±0.27 and 1.55±0.19, respectively. Conclusion BDE-209 increased expression of proteins in the MAPK pathway and decreased expression of the BTB tight junction protein claudin-11 in testicular tissue. It also caused ultrastructural damage to the Sertoli cell BTB tight junctions.This suggested that BDE-209 might damage Sertolicells BTB through effects on the MAPK pathway.

Objective To study changes in expression of claudin-11 and proteins related to mitogen-activated protein kinase (MAPK) signaling pathways, as well as the ultrastructure of the blood testis barrier(BTB), in male ICR mice exposed to decabromodiphenyl ether (BDE-209). Methods Fifty-two mice, 4 weeks of age, weighing 15-21 g, were provided with adaptive feeding for 1 week. Mice were randomly divided into 4 groups, named control, low-dose, medium-dose and high-dose groups. The treated groups received BDE-209, by intragastric gavage, at doses, respectively, of 100, 300 and 500 mg/kg. Mice were sacrificed after 6 weeks and organs harvested on ice, weighed and stored at-80 °C. The ultrastructure of testicular tissues was examined by electron microscopy. Western blotting was used to detect proteins related to the MAPK pathway, including p38 mitogen activated protein kinase (p38), phosphorylated p38 (p-p38), extracellular regulated protein kinase 1/2 (ERK1/2) , phosphorylated ERK1/2 (p-ERK1/2) , c-jun N-terminal kinase (JNK), phosphorylated JNK (p-JNK) and the BTB tight junction protein claudin-11. Analyze the difference between each groups. Results At sacrifice, the body weights in each treated group were compared with those in the control group weighing (41.14 ± 0.60) g. Compared with controls, body weights were significantly different (P<0.05) in the middle dose, at (39.97 ± 0.66) g and high dose, at (39.98± 0.55) g in control group. The coefficients of the testis were significantly lower (P<0.05) in each treated group than in controls, with values of (0.37±0.0)%, (0.31±0.05)% and (0.31±0.04)% for low- dose, medium-dose and high-dose groups, respectively. The epidymus coefficient values were also significantly lower than controls (P<0.05), with values of (0.16±0.06)%, (0.11±0.05)% and (0.07±0.03)%, respectively in the same three dose groups. Electron microscopy ultrastructure showed that, compared with the control group, the testes in the middle and high dose groups had closely connected fractures, cell edema and more vacuoles. Compared with in the control group, levels of p-p38 and p-JNK in testicular tissue were significantly increased (P<0.05). In the control group and in low-, medium- and high-dose groups, the p-p38/p38 ratios were 1.35±0.13, 3.46±0.10, 5.71±0.26 and 4.79±0.21, respectively. The corresponding p-JNK/JNK ratios were 2.07±0.0, 4.77±0.18, 3.63±0.06 and 4.85±0.15. Claudin-11 levels were significantly lower (P<0.05) than control values in each dosed group. The corresponding values in control, low-dose, medium-dose and high-dose groups were 8.33±0.36, 2.06±0.27, 3.37±0.27 and 1.55±0.19, respectively. Conclusion BDE-209 increased expression of proteins in the MAPK pathway and decreased expression of the BTB tight junction protein claudin-11 in testicular tissue. It also caused ultrastructural damage to the Sertoli cell BTB tight junctions.This suggested that BDE-209 might damage Sertolicells BTB through effects on the MAPK pathway.