Objective Based on the endoplasmic reticulum stress(ERS)inositol-requiring enzyme-1α(IRE1α)/apoptosis signal-regulated kinase 1(ASK1)/c-Jun N-terminal kinase(JNK)pathway to investigate the intervention effect of Ziziphi Spinosae Semen(ZSS)-Albiziae Flos(AF)on the depression model of rats,which were prepared by solitary rearing combined with chronic unpredictable mild stress(CUMS).Methods A total of 144 rats were randomly divided into normal group,model group,high-,medium-and low-dose groups of ZSS-AF,and Venlafaxine group.In addition to the normal group,the rats in other groups were isolated for 21 days combined with CUMS to prepare the depression model.The behavioral changes of rats were observed by open field test and Morris water maze test.The ultrastructural changes of hippocampal neurons were observed by transmission electron microscope.TUNEL staining was used to observe the apoptosis of nerve cells in hippocampus.The protein expression levels of IRE1α,phosphorylated(P)-IRE1α,ASK1,P-ASK1,JNK,P-JNK,B cell lymphoma-2(Bcl-2),Bcl-2 associated X protein(Bax)and cysteme aspartate specific protease-3(Caspase-3)in hippocampus were detected by Western Blot.The mRNA expression levels of IRE1α,ASK1,JNK,Bax,Bcl-2 and Caspase-3 in hippocampus were detected by Real-Time PCR.Results Compared with the normal group,the scores of horizontal movement and vertical movement in the open field test of rats in the model group were decreased(P＜0.01).In the water maze test,the escape latency was increased and the number of crossing the original platform was decreased(P＜0.01).The number of hippocampal apoptosis was increased(P＜0.01).The protein expression levels of P-IRE1 α/IRE1 α,P-ASK1/ASK1,P-JNK/JNK,Bax,Caspase-3 and mRNA expressions of IRE1α,ASK1,JNK,Bax,Caspase-3 in hippocampus were increased,while the protein and mRNA expression levels of Bcl-2 were decreased(P＜0.01).Compared with model group,the scores of horizontal movement and vertical movement in the open field test of rats in each dose ZSS-AF groups and Venlafaxine group were increased(P＜0.01).In the water maze test,the escape latency was decreased and the times of crossing the original platform was increased(P＜0.01).The number of hippocampal apoptosis was decreased(P＜0.01).The mRNA expression levels of P-IRE1α/IRE1α,P-ASK1/ASK1,P-JNK/JNK,Bax,Caspase-3 protein and IRE1α,ASK1,JNK,Bax,Caspase-3 in hippocampus were decreased,while the protein and mRNA expression levels of Bcl-2 were increased(P＜0.05,P＜0.01).The effect of medium-dose ZSS-AF group was better than that of high-and low-dose groups.Conclusion ZSS-AF may play an antidepressant role by regulating IRE1α/ASK1/JNK pathway of endoplasmic reticulum stress.

Hypertrophic scars are unfavorable skin diseases characterized by excessive collagen deposition. Although systemic treatments exist in clinic to manage hypertrophic scars, they pose significant side effects and tend to lose efficacy over prolonged applications. Traditional Chinese medicine (TCM) offers as a promising candidate to treat pathological scars. A large number of TCMs have been studied to show anti-scarring effect, however, the natural barrier of the skin impedes their penetration, lowering its therapeutic efficacy. Herein, we reported the use of dissolvable hyaluronic acid (HA) microneedles (MNs) as a vehicle to aid the transdermal delivery of therapeutic agent, a model TCM called shikonin for the treatment of hypertrophic scars. Here, shikonin was mixed with HA to make MNs with adequate mechanical strength for skin penetration, making its dosage controllable during the fabrication process. The therapeutic effect of the shikonin HA MNs was studied

Objective: To investigate the expression of INPP4B in gastric cancer and its relationship with clinicopathological features and prognosis. Methods: The expressions of INPP4B mRNA in fresh cancer tissues of 36 patients with gastric cancer and the paracancerous normal gastric mucosa tissues in the Affiliated Cancer Hospital of Shanxi Medical University between July 2014 and December 2014 were detected by using real-time quantitative polymerase chain reaction (RT-qPCR). The expressions of INPP4B protein and its downstream molecule phosphorylation AKT (p-AKT) in paraffin-embedded tumor tissues and the corresponding margin tissues of 49 gastric cancer patients between January 2010 and December 2010 were detected by using immunohistochemistry. The relationship between the expression of INPP4B and clinicopathological features and prognosis was analyzed. Results: RT-qPCR results showed that the expression level of INPP4B mRNA was 0.21±0.04 compared with adjacent cancer normal tissues (t = -2.208, P < 0.05). Immunohistochemistry showed that INPP4B protein was highly expressed in normal margin tissues and lowly expressed in tumor tissues. There was a statistical difference in the positive intensity score between the two groups (u = 4.70, P < 0.01). However, p-AKT protein was overexpressed in tumor tissues and underexpressed in normal margin tissues. There was a statistical difference in the positive intensity score between the two groups (u = 5.77, P < 0.01). The expression of INPP4B and p-AKT protein was negatively correlated (r = -0.644, P < 0.01). The positive expression rate of INPP4B protein in gastric cancer patients was 34.7% (17/49). There were no statistical differences of the positive expression rate of INPP4B protein in gender, age, pathological type, depth of invasion and lymph node metastasis (all P > 0.05). The median overall survival time of patients with INPP4B negative expression was 47 months, and that of patients with INPP4B positive expression was 48 months, and there was no statistical difference (P > 0.05). Conclusion The expression of INPP4B in gastric cancer tissue is low, which may play a role of tumor suppressor in the occurrence and development of gastric cancer by affecting the activity of AKT.