ObjectiveTo investigate the effect of mitochondrial calcium uniporter （MCU） on the cytoskeleton of pancreatic ductal epithelial cells in a mouse model of acute pancreatitis （AP） induced by caerulein （CAE）， to analyze the role of MCU in the development of AP， and to provide a theoretical basis for clinical treatment. MethodsIn the in vivo experiment， wild-type male C57BL6/J mice， aged 4 weeks， were randomly divided into control group and AP group， with 6 mice in each group. The mice in the AP group were given intraperitoneal injection of CAE to establish a model of AP， and those in the control group were given intraperitoneal injection of an equal volume of normal saline. Serum and pancreatic tissue samples were collected after 24 hours of modeling. HE staining was used to observe pancreatic histopathological changes； Western Blot was used to measure the expression levels of MCU， glutathione peroxidase 4 （GPX4）， and acyl-CoA synthetase long chain family member 4 （ASCL4）； kits were used to measure the serum level of amylase. In the in vitro experiment， the human pancreatic ductal epithelial cell line HPDE6-C7 was co-cultured with CAE for 24 hours to establish an in vitro AP model， and the cells were divided into control group， CAE group， RR （an MCU activity inhibitor） group， CAE+RR group， Fer-1 （an ferroptosis inhibitor） group， CAE+Fer-1 group， Erastin （an ferroptosis inducer） group， and CAE+Erastin group. CCK-8 assay was used to observe the influence of different agents on cell viability； Western Blot was used to measure the expression levels of MCU， GPX4， and ASCL4； immunofluorescence assay was used to measure reactive oxygen species （ROS）， actin cytoskeleton， and monolayer permeability； kits were used to measure the concentrations of malondialdehyde （MDA）， glutathione （GSH）， Fe²⁺， and total iron. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for comparison between two groups. ResultsIn the in vivo experiment， compared with the control group， the AP group had significant increases in pancreatic histopathological score， the serum level of amylase， and the expression levels of MCU and ASCL4， as well as a significant reduction in the expression of GPX4 （all P<0.05）. In the in vitro experiment， compared with the control group， the CAE group had significant increases in the expression levels of MCU and ASCL4， a significant reduction in the expression of GPX4， and significant increases in the concentrations of Fe²⁺， total iron， and MDA， the green fluorescence intensity of ROS， and monolayer permeability， as well as a significant reduction in the concentration of GSH （all P<0.05）， with the presence of actin cytoskeleton disruption. Compared with the CAE group， the CAE+RR group had a significant increase in the expression level of GPX4， a significant reduction in the expression level of ASCL4， and significant reductions in the concentrations of Fe²⁺， total iron， and MDA， the green fluorescence intensity of ROS， and monolayer permeability and a significant increase in the concentration of GSH （all P<0.05）， with alleviation of actin cytoskeleton disruption. Compared with the CAE group， the CAE+Fer-1 group had significant reductions in the concentrations of Fe²⁺， total iron， and MDA， the green fluorescence intensity of ROS， and monolayer permeability and a significant increase in the concentration of GSH （all P<0.05）， with alleviation of actin cytoskeleton disruption. Compared with the CAE group， the CAE+Erastin group had significant increases in the concentrations of Fe²⁺， total iron， and MDA， the green fluorescence intensity of ROS， and monolayer permeability and a significant reduction in the concentration of GSH （all P<0.05）， with aggravation of actin cytoskeleton disruption. ConclusionDuring the onset of AP， MCU mediates oxidative stress-induced ferroptosis and leads to the disruption of the pancreatic ductal epithelial barrier， which may be one of the possible pathogeneses of AP.

Marsdenia tenacissima injection, a standard Marsdenia tenacissima extract (MTE), has been approved as an adjuvant therapeutic agent for various cancers. Our previous study showed that MTE inhibited the proliferation and metastasis of prostate cancer (PCa) cells. However, the underlying mechanisms and active ingredients of MTE against PCa were not completely understood. This study revealed that MTE induced significant decreases in cell viability and clonal growth in PCa cells. In addition, MTE induced the apoptosis of DU145 cells by reducing the mitochondrial membrane potential and increasing the expression of Cleaved Caspase 3/7, Cyt c, and Bax. In vivo, DU145 xenografted NOD-SCID mice treated with MTE showed significantly decreased tumor size. TUNEL staining and Western blot confirmed the pro-apoptotic effects of MTE. Network pharmacology analysis collected 196 ingredients of MTE linked to 655 potential targets, and 709 PCa-associated targets were retrieved, from which 149 overlapped targets were screened out. Pathway enrichment analysis showed that the HIF-1, PI3K-AKT, and ErbB signaling pathways were closely related to tumor apoptosis. Western blot results confirmed that MTE increased the expression of p-AKT^Ser473 and p-GSK3β^Ser9, and decreased the expression of p-STAT3^Tyr705in vitro and in vivo. A total of 13 compounds in MTE were identified by HPLC-CAD-QTOF-MS/MS and UPLC-QTOF-MS/MS. Molecular docking analysis indicated that six compounds may interact with AKT, GSK3β, and STAT3. In conclusion, MTE induces the endogenous mitochondrial apoptosis of PCa by regulating the AKT/GSK3β/STAT3 signaling axis, resulting in inhibition of PCa growth in vitro and in vivo.
Mice ; Animals ; Male ; Humans ; Mice, Inbred NOD ; Mice, SCID ; Marsdenia ; Proto-Oncogene Proteins c-akt ; Glycogen Synthase Kinase 3 beta ; Molecular Docking Simulation ; Phosphatidylinositol 3-Kinases ; Tandem Mass Spectrometry ; Prostatic Neoplasms ; Apoptosis ; STAT3 Transcription Factor

Objective:To study the efficacy of different systemic chemotherapy regimens as first-line and second-line therapy and to determine the prognostic factors for patients with advanced biliary tract cancer.Methods:The clinical data of patients with advanced biliary tract cancer who underwent systemic chemotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from January 2011 to December 2018 were studied. The efficacy of chemotherapy on objective response rate (ORR) and disease control rate (DCR) were evaluated. Potential prognostic factors for survival were studied using the Cox proportional hazards models.Results:Of 151 patients enrolled into this study, there were 75 males and 76 females, with ages ranging from 31 to 77 years (median 58 years). Two treatment protocols were used: (1) 104 patients received a gemcitabine-based regimen (combined with platinums or fluorouracils) or a combination of platinums and fluorouracils, while (2) 47 patients received a combination of albumin-bound paclitaxel and S-1. The corresponding ORR for each group were 15.4%(16/104) and 27.6%(13/47), respectively, and the DCR were 65.4%(68/104) and 72.3%(34/47), respectively. Of 58 evaluable patients who received chemotherapy as a second-line therapy, 31 patients received the regimen containing gemcitabine, platinums or fluorouracils with an ORR of 3.2% (1/31) and a DCR of 35.5%(11/31); a total of 18 patients received the taxanes-based regimen with an ORR of 11.1%(2/18) and a DCR of 38.9%(7/18); 9 patients received the irinotecan-based regimen with an ORR of 22.2%(2/9) and a DCR of 44.4%(4/9). Univariate analysis showed positive liver metastasis and elevated carbohydrate antigen (CA)19-9 level to be significantly correlated with worse survival outcomes ( HR=1.540, 95% CI: 1.019-2.328, P=0.040 and HR=1.892, 95% CI: 1.123-3.188, P=0.017). Conclusion:For patients with advanced biliary tract cancer, in addition to the conventional regimens containing gemcitabine, platinums and fluorouracils, the combination of albumin-bound paclitaxel and S-1 was shown to be an effective chemotherapeutic regimen for these patients. Second-line chemotherapy was insufficient and ineffective, and an irinotecan-based regimen deserves to be further investigated. Liver metastasis and elevated CA19-9 level were worse prognosis after chemotherapy for patients with advanced biliary tract cancer.

Objective:To investigate the relationship between plasma levels of complements before treatment and the clinicopathological feathers and prognoses of diffuse large B-cell lymphoma (DLBCL) patients treated with Rituximab (R)-CHOP or R-CHOP-like therapy.Methods:The clinicopathological data of 105 DLBCL patients treated in cancer Hospital of Chinese Academy of Medical Sciences from 2010 to 2016 were collected. The plasma samples from 105 DLBCL patients treated with R-CHOP or R-CHOP-like therapy and 80 healthy controls were used to detect 34 complement levels before treatment by utilizing antibody microarray. The relationship between plasma levels of complements and the clinicopathological feathers and prognosis of DLBCL patients were analyzed.Results:The signal values of C1QA and CR1L in patients with international prognostic index (IPI) scores of 3-5 were 1 261.43±138.9 and 2 214.69±98.58, respectively, higher than 950.79±80.19 and 984.67±121.79 in patients with IPI scores of 0~2 (both P<0.05). The levels of C1QA and CR1L in the non-complete response (CR) group were 1 165.43±98.56 and 2 263.13±145.63, respectively, higher than 914.70±100.77 and 1 821.34±84.68 in the CR group (both P<0.05). Cox regression analysis showed that elevated C1QA signal value was associated with poor progression-free survival (PFS) and poor overall survival (OS) (PFS: HR=2.063, 95% CI: 1.220-3.489, P=0.007; OS: HR=2.23, 95% CI: 1.036~4.798, P=0.040). After IPI correction by Cox multivariate model, the elevated C1QA signal value was still correlated with poor PFS ( HR=1.765, 95% CI 1.034~3.013, P=0.037). Conclusions:The baseline plasma levels of C1QA and CR1L are correlated with IPI scores and therapeutic effects of DLBCL patients treated with R-CHOP. The baseline plasma level of C1QA has a certain predictive value for the prognostic evaluation of DLBCL.

Objective:To investigate the relationship between plasma levels of complements before treatment and the clinicopathological feathers and prognoses of diffuse large B-cell lymphoma (DLBCL) patients treated with Rituximab (R)-CHOP or R-CHOP-like therapy.Methods:The clinicopathological data of 105 DLBCL patients treated in cancer Hospital of Chinese Academy of Medical Sciences from 2010 to 2016 were collected. The plasma samples from 105 DLBCL patients treated with R-CHOP or R-CHOP-like therapy and 80 healthy controls were used to detect 34 complement levels before treatment by utilizing antibody microarray. The relationship between plasma levels of complements and the clinicopathological feathers and prognosis of DLBCL patients were analyzed.Results:The signal values of C1QA and CR1L in patients with international prognostic index (IPI) scores of 3-5 were 1 261.43±138.9 and 2 214.69±98.58, respectively, higher than 950.79±80.19 and 984.67±121.79 in patients with IPI scores of 0~2 (both P<0.05). The levels of C1QA and CR1L in the non-complete response (CR) group were 1 165.43±98.56 and 2 263.13±145.63, respectively, higher than 914.70±100.77 and 1 821.34±84.68 in the CR group (both P<0.05). Cox regression analysis showed that elevated C1QA signal value was associated with poor progression-free survival (PFS) and poor overall survival (OS) (PFS: HR=2.063, 95% CI: 1.220-3.489, P=0.007; OS: HR=2.23, 95% CI: 1.036~4.798, P=0.040). After IPI correction by Cox multivariate model, the elevated C1QA signal value was still correlated with poor PFS ( HR=1.765, 95% CI 1.034~3.013, P=0.037). Conclusions:The baseline plasma levels of C1QA and CR1L are correlated with IPI scores and therapeutic effects of DLBCL patients treated with R-CHOP. The baseline plasma level of C1QA has a certain predictive value for the prognostic evaluation of DLBCL.

Objective To investigate the effect of Anerdian type III solution on the treatment of acute gouty monoarthritis. Methods Total 108 cases of acute gouty monoarthritis were divided into two groups according to the method of random number table, including 56 cases in the Anerdian group and 53 cases in the Votalin group, respectively. The Anerdian group was applied Anerdian type III solution to compress the swelling joint wet for 30 minutes, while the Votalin group was given Votalin Emulgel for external application in the swollen joint. Then the scores of pain and redness were calculated, and the effects of local treatment were compared directly before and after the treatment, and these variables were also compared after 7 days. Results 24 hours and 72 hours after the treatment, the pain score in the Anerdian group was 3.44 ± 0.89 and 2.43 ± 0.73 (t=2.375, 3.393, P<0.01), while the pain score in the Votalin group was 3.85 ± 0.74 and 3.14 ± 0.68 (t=2.208, 3.120, P<0.01), respectively, which referred to improvement in both groups.And the score of redness in the Anerdian group was 1.57 ± 0.70 and 1.13 ± 0.35 (t=0.589, 0.964, P<0.01), while the score of redness in the Votalin group was 1.95 ± 0.73 and 1.61 ± 0.49 (t=0.151, 0.623, P=0.091, P<0.01) respectively. 24 hours and 72 hours after the treatment, the score of redness in the Anerdian group was smaller than that in the Votalin Group (t=3.379, 4.290, P<0.01). In Anerdian group, local treatment showed fully cured in 28 cases, marked effective in 15 cases, effective in 11 cases, not effective in 2 case, and total effective rate was 96.4% (54/56) after 7 days′treatment, while in Votalin group, local treatment revealed fully cured in 24 cases, marked effective in 11 cases, effective in 8 cases, not effective in 9 case, and total effective rate was 83.0% (44/53). There was statistically significant difference between the two groups in local treatment ( χ2=4.019, P<0.05). Conclusion Anerdian type III solution can alleviate the symptoms of acute gouty unilateral arthritis quickly. It hasbetter curative effect on local treatment of acute gouty monoarthritis than Votalin.

Objective To discuss the clinical effect of the phase-one treatment scheme for traumatic osteomyelitis in tibia by combining flap,vancomycin-loaded calcium sulfate and autogenous iliac bone.Methods From January,2009 to July,2014,49 patients which had traumatic osteomyelitis in tibia and met the inclusive criteria were investigated and treated.By taking these patients as treatment group A(34 cases),they were treated by adopting the phase-one treatment scheme of combing tissue flap,vancomycin-loaded calcium sulfate and autogenous iliac bone.Fifteen patients who were treated by using the phase-one treatment scheme,namely,removing the lesion,implanting vancomycin-loaded calcium sulfate and repairing the defect by means of tissue flap,were chosen as control group B.Concerning treatment group A,drainage fluid was collected after operation every day to measure the concentration of vancomycin until drainage tube was removed.All the patients were followed up to study the following indexes:the standing time of drainage tube,the healing time of fracture,infection control rate,bone nonunion rate and other complications.Results All cases were followed up during 17 to 40 months after operation and no amputation was conducted for the affected limb.To repair soft tissue defect,flap and direct suture were adopted for 25 and 9 cases respectively in group A;The results indicated that all flaps survived,the poor healing of flap defect was observed for 2 cases which were healed after dressing change.However,to repair soft tissue defect,all group B cases used flaps;results revealed that distal flap necrosis was found in 2 cases applying neurocutaneous flap,with defect exudation and infection while the 2 cases were cured after debridement and dressing change without performing a second flap operation.In group A,3 cases recurred during 5 months to 2 years after operation;in group B,it was 1;other complications included pintract infection,nonunion,numbness of anterolateral thigh,hematocele in iliac 1 region.In group B,refracture occurred for 2 cases at the original lesion location 18 and 25 months after healing and was cured after plate refixation and the graft of autogenous iliac bone;intraoperative pathology validated no recurrence of osteomyelitis.The standing time of drainage tube was (12.53±4.56) days on average for group A while (17.07±3.87) days for group B;The difference was statistically significant (P＜0.05).The healing time of fracture was (6.20±2.16) months on average for group A while(8.36±2.84) months for group B.The difference was statistically significant(P＜0.05).Conclusion In one stage treatment of localized and diffused traumatic osteomyelitis,the scheme of combining tissue flap,vancomycin-loaded calcium sulfate and autogenous iliac bone effectively shortened the healing time of fracture,increased the healing strength,and reduced the exudation after operation,without increasing infection recurrence rate.The scheme was superior to merely implanting vancomycin-loaded calcium sulfate.

Objective:A questionnaire for the compliance with moxibustion was designed based on the 4-item Morisky scale, and the reliability and validity of the questionnaire was investigated.Methods:A modified Morisky scale was designed based on the 4-item Morisky scale for the compliance with moxibustion, and 146 patients having received moxibustion for over 2 weeks were investigated using this scale to evaluate their compliance with moxibustion; the internal equity and the construct validity of the scale were statistically analyzed.Results:The analysis of reliability showed that in item of internal consistency, the Cronbach's α was 0.72 and the split-half coefficient was 0.71, the correlation coefficients between the 4 component scores and the total score ranged 0.67-0.80, and the between-component correlation coefficients ranged 0.24-0.56; the exploratory factor analysis (EFA) totally extracted 1 common factor, and the explicable variation was 55.02%, and the loads of the 4 items were respectively 0.82, 0.81, 0.74 and 0.58.Conclusion:The reliability and validity of the modified Morisky scale for the compliance with moxibustion are acceptable, while several items need further modification and improvement in the expression and content.

An App for Android intelligent mobile phone to recite prescriptions in rhyme and learn infused pre-scriptions of traditional Chinese medicine was developed in order to meet the requirement of students majoring in traditional Chinese medicine and lovers of traditional Chinese medicine, which can show the assistant and guide of prescriptions in rhyme by different colors. An interface linked with each corresponding traditional Chinese medicine was added into the App to show its picture, properties, effect and application for the interaction between database server and mobile phone users and the aim to recite prescriptions of traditional Chinese medicine and learn tradi-tional Chinese medicine.

Apoptosis refers to the programmed death process of cells modulated by genes. It plays an important role in promoting the evolution of organisms, regulating the development of multiple systems, and maintaining the stability of internal environment. The major apoptosis pathways include mitochondrial pathways, death receptor pathways, and endoplasmic reticulum pathways. With the rapid development of the scientific research on acupuncture, it’s revealed that cell apoptosis should be closely related to the action of acupuncture. So far, the major apoptosis factors involved in relevant researches are P53, Bcl-2 family, Cyt-C, Caspase, Fas/Fasl, TNFR1/TNF-?, and FADD-Caspase8, and PERK, etc. Via influencing these apoptosis factors or genes, acupuncture can produce various effects in improving tissue ischemia, protecting neural cells, reducing inflammation, and correcting endocrine disorders. This article summarized and reviewed the apoptosis pathways and key factors related to the action of acupuncture, to provide some beneficial references for future studies.