Protein disulfide isomerase (PDI) is one of thiol-disulfide oxidoreductases that mainly located in the endo?plasmic reticulum (ER). It is generally known that PDI caralyzes the formation,rearrangement,breakage of disulfide bonds, and this enzyme is effective in regulation of protein folding. Now it is also known as a biomarker of cardiovascular disease. Protein disulfide isomerase can reduce infarct size and myocardial apoptosis in acute myocardial infarction (AMI). PDI can also improve changes of cardiac vulnerability in diabetic cardiomyopathy (DCM). Further more, it is also shown that PDI play an important role in hypertension and thrombosis. Therefore, this paper review the effects of protein disulfide isomerase in cardiovascular diseases.

This study was aimed to summarize the clinical medication rule of professor Shi Qi in the treatment of cervical spondylosis of vertebral artery type (CSA),in order to explore the academic ideas.A total of 265 CSA cases from professor Shi Qi's outpatient clinic were collected in Longhua Hospital from 2009 to 2015.Frequency analysis and cluster analysis were conducted on used herbal medicine from included cases by SPSS 21.00 software.The results showed that there were a total of 202 types of herbs used.The five most commonly used herbs were Rhizoma Ligustici Wallichii,Radix bupleuri,Radix Achyranthis Bidentatae,Codonopsis and Gastrodia elata.The cluster analysis revealed that professor Shi Qi frequently used Huo-Xue Hua-Yu herbs,Bu-Xu herbs,Ping-Gan Xi-Feng herbs,Qu-Feng-Shi herbs.Sheng-Yu decoction and Tian-Ma Gou-Teng decoction were the core prescriptions used by professor Shi Qi in the treatment of CSA.It was concluded that the cluster analysis showed that academic ideas of professor She in the treatment of CSA was to pay equal attention to both qi and blood,to focus on liver and kidney,as well as to remove phlegm and blood stagnation,to treat both the branch and the root.The cluster analysis revealed a certain medication rule of professor Shi Qi in the treatment of CSA.It can be used as guidance in the clinical practice.

Objective:To investigate the role of hydrogen-rich salt water in improving depression-like symptoms and its possible molecular mechanism in rats.Methods:The experiment was divided into two stages. In the first stage, 35 healthy male SD rats were randomly divided into control group, model group, high-dose group, medium-dose group, and low-dose group ( n=7); rats in the control group and model group were gavaged with 8 mL/kg normal saline per d, and rats in the high-dose group, medium-dose group, and low-dose group were fed with 8 mL/kg hydrogen-rich saline water (containing 2, 1, and 0.5 ppm hydrogen) per d; except for the control group, the other groups were depressed with chronic unpredictable mild stimulation (CUMS) for 4 weeks. In the second stage, 30 healthy male SD rats were randomly divided into hydrogen water group, hydrogen water+fluoxetine group, and nuclear factor erythroid 2-related factor 2 (Nrf2) inhibition group ( n=10); optimal hydrogen concentration (0.8 ppm) hydrogen-rich saline water (8 mL/kg) per d was given to rats of these 3 groups by gavage; fluoxetine (5 mg/kg) by gavage was given to the hydrogen-water+fluoxetine group, and all-transretinoic acid (10 mg/kg) by gavage was given to the Nrf2 inhibition group; CUMS was given for 4 weeks in these 3 groups. Rats were weighed at fixed times at each weekend. Four weeks after intervention, the total distance and average speed of rats in each group were determined by open field test. After open field test, blood was collected from the orbital veins from all rats; serum superoxidase dismutase (SOD) and malondialdehyde (MDA) contents were determined by ELISA. The expressions of brain-derived neurotrophic factor (BDNF), heme oxygenase-1 (HO-1), Nrf2, and phosphorylated Nrf2 (p-Nrf2) in the hippocampal CA3 region were detected by Western blotting. Results:(1) In the first stage, after 3 and 4 weeks of intervention, as compared with the model group, the body weight of the rats in the high-dose group, medium-dose group, and low-dose group increased significantly ( P<0.05). As compared with the model group, the medium-dose group, and low-dose group had significantly increased total distance and average speed, significantly increased serum SOD content, significantly decreased serum MDA content, significantly increased BDNF and HO-1 expressions and decreased p-Nrf2 expression in the CA3 region of the hippocampus ( P<0.05). (2) In the second stage, after 3 and 4 weeks of intervention, as compared with the Nrf2 inhibition group, the body weight of the hydrogen water group and hydrogen water+fluoxetine group increased significantly ( P<0.05). As compared with the Nrf2 inhibition group, the hydrogen water group and hydrogen water+fluoxetine group had significantly increased total distance and average speed, significantly increased serum SOD content, significantly decreased serum MDA content, statistically increased BNDF and HO-1 expressions in the CA3 region of the hippocampus, and the hydrogen water+fluoxetine group had significantly increased Nrf2 and p-Nrf2 expressions in the CA3 region of the hippocampus ( P<0.05). As compared with the hydrogen water group, the hydrogen water+fluoxetine group had significantly increased BNDF and HO-1 expressions and increased p-Nrf2 expression in the CA3 region of the hippocampus ( P<0.05). Conclusion:Hydrogen-rich salt water can increase the serum SOD and reduce the serum MDA, increase the BDNF and HO-1 protein expressions in the hippocampal areas of depressed rats, thereby improving the depression-like symptoms; the synergistic effect of hydrogen-rich saline water and fluoxetine on anti-depression may be related to antioxidant effect of Nrf2 signaling.

Objective This study aimed to design and optimize the water extraction process for Chuantieling (喘贴灵, CTL) based on the concept of quality by design (QbD). Methods The single-factor experiments were used to select the best experimental points of CTL water extraction. On this basis, the transfer rate of ephedrine hydrochloride and sinapine thiocyanate, and the yield of the extract were evaluated as the evaluation indicators. The liquid-solid ratio, extraction time, and pH value were selected as the main factors to carry out the Box-Behnken design (BBD). A mathematical model of the critical process parameters (CPPs) and critical quality attributes (CQAs) was established, the interaction between CQAs and CPPs was examined, and the CTL extraction process design space was established and optimized, which guaranteed the stability of the process. The high performance liquid chromatography (HPLC) was used to analyze the main active compounds in the CTL extract. Results Through single-factor experiments, the best experimental parameters were found to be a liquid-solid ratio of 8∶1, extraction time of 90 min, pH value of 4, and extraction times of three. The experimental variance analysis results of the BBD showed that the P value of the regression model was less than 0.05, and the lack-of-fit value was greater than 0.01, indicating that the constructed model had good predictive ability. The operating space of the CPPs of the CTL water extraction process was combined with the actual production situation. In the production situation, the best extraction process was nine times of water addition, 72 min of extraction time, and 4.5 of pH value. The HPLC results showed that the peak areas of ephedrine hydrochloride, sinapine thiocyanate, tetrahydropalmatine, methyl eugenol, cinnamaldehyde, and 6-gingerol in the CTL extract accounted for 0.94%, 14.32%, 0.78%, 31.23%, 0.34%, and 0.44% of the total peak area, respectively. Conclusion The water extraction process design space of CTL based on QbD was conducive to actual production operations, ensuring the stability of the process.

Objective:To investigate whether IL-6 using in early pregnancy can improve the pregnancy outcome of recurrent spontaneous abortion(RSA)mice and its relevant mechanism,providing new ideas for RSA clinical treatment.Methods:CBA/J×DBA/2 RSA model mice were constructed,and randomly divided the pregnant mice into five groups:control group,0.1 ng/ml IL-6 group,1 ng/ml IL-6 group,10 ng/ml IL-6 group and 100 ng/ml IL-6 group.IL-6 was not injected in control group,while different concentra-tions of IL-6 were respectively injected into other groups on the 0.5 day of pregnancy.Pregnant rats were killed at 13.5 d and the embryo loss rate was calculated,the placental tissue was taked out,and expressions of IL-6 and indoleamine 2,3-dioxygenase(IDO)in tissues were detected by Western blot.Results:Embryo absorption rates of 0.1 ng/ml IL-6 group,1 ng/ml IL-6 group,10 ng/ml IL-6 group and 100 ng/ml IL-6 group were obviously lower than that in control group(P=0.002 4,P=0.007 0,P=0.027 0,P=0.031 0).IL-6 of exogenous injection was positive correlated with that expressed in mice placental tissue(r=0.791,P=0.000 052).IL-6 concentration of exogenous injection was between 0～1 ng/ml,which was positively correlated with IDO expression in placental tissue(r=0.868,P<0.000 1),IL-6 was positively correlated with IDO expressed in placental tissue(r=0.982,P<0.000 1).IL-6 concentration of exogenous injection was between 1～100 ng/ml,which was inversely correlated with IDO expression(r=-0.725,P=0.002),and IL-6 was inversely correlated with IDO expressed in placental tissue(r=-0.972,P<0.000 1).Conclusion:A single intraperitoneal injection of specific concentration of exogenous IL-6 to RSA mice can reduce embryo absorption rate of mice and modify their pregnancy outcome,which possible mecha-nism is the exogenous IL-6 induces expressions of IL-6 and IDO for a long term.Whether the IDO expression in placental tissue in-crease or not can be regarded as a mark for whether the specific concentration IL-6 can protect the pregnancy or not.

Objective:To investigate the prognosis of patients with initially resectable gastric cancer liver metastasis (GCLM) who were treated by different modalities, and analyze the influencing factors for prognosis of patients.Methods:The retrospective cohort study was conducted. The clinicopathological data of 327 patients with initially resectable GCLM who were included in the database of a nationwide multicenter retrospective cohort study on GCLM based on real-world data from January 2010 to December 2019 were collected. There were 267 males and 60 females, aged 61(54,68)years. According to the specific situations of patients, treatment modalities included radical surgery combined with systemic treatment, palliative surgery combined with systemic treatment, and systemic treatment alone. Observation indicators: (1) clinical characteristics of patients who were treated by different modalities; (2) prognostic outcomes of patients who were treated by different modalities; (3) analysis of influencing factors for prognosis of patients with initially resectable GCLM; (4) screening of potential beneficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and Log-Rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the COX proportional hazard regression model. The propensity score matching was employed by the 1:1 nearest neighbor matching method with a caliper value of 0.1. The forest plots were utilized to evaluate potential benefits of diverse surgical combined with systemic treatments within the population. Results:(1) Clinical characteristics of patients who were treated by different modalities. Of 327 patients, there were 118 cases undergoing radical surgery plus systemic treatment, 164 cases undergoing palliative surgery plus systemic treatment, and 45 cases undergoing systemic treatment alone. There were significant differences in smoking, drinking, site of primary gastric tumor, diameter of primary gastric tumor, site of liver metastasis, and metastatic interval among the three groups of patients ( P<0.05). (2) Prognostic outcomes of patients who were treated by different modalities. The median overall survival time of the 327 pati-ents was 19.9 months (95% confidence interval as 14.9-24.9 months), with 1-, 3-year overall survival rate of 61.3%, 32.7%, respectively. The 1-year overall survival rates of patients undergoing radical surgery plus systemic treatment, palliative surgery plus systemic treatment and systemic treatment alone were 68.3%, 63.1%, 30.6%, and the 3-year overall survival rates were 41.1%, 29.9%, 11.9%, showing a significant difference in overall survival rate among the three groups of patients ( χ2=19.46, P<0.05). Results of further analysis showed that there was a significant difference in overall survival rate between patients undergoing radical surgery plus systemic treatment and patients undergoing systemic treatment alone ( hazard ratio=0.40, 95% confidence interval as 0.26-0.61, P<0.05), between patients undergoing palliative surgery plus systemic treatment and patients under-going systemic treatment alone ( hazard ratio=0.47, 95% confidence interval as 0.32-0.71, P<0.05). (3) Analysis of influencing factors for prognosis of patients with initially resectable GCLM. Results of multivariate analysis showed that the larger primary gastric tumor, poorly differentiated tumor, larger liver metastasis, multiple hepatic metastases were independent risk factors for prognosis of patients with initially resectable GCLM ( hazard ratio=1.20, 1.70, 1.20, 2.06, 95% confidence interval as 1.14-1.27, 1.25-2.31, 1.04-1.42, 1.45-2.92, P<0.05) and immunotherapy or targeted therapy, the treatment modality of radical or palliative surgery plus systemic therapy were independent protective factors for prognosis of patients with initially resectable GCLM ( hazard ratio=0.60, 0.39, 0.46, 95% confidence interval as 0.42-0.87, 0.25-0.60, 0.30-0.70, P<0.05). (4) Screening of potentinal beneficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment. Results of forest plots analysis showed that for patients with high-moderate differentiated GCLM and patients with liver metastasis located in the left liver, the overall survival rate of patients undergoing radical surgery plus systemic treatment was better than patients undergoing palliative surgery plus systemic treatment ( hazard ratio=0.21, 0.42, 95% confidence interval as 0.09-0.48, 0.23-0.78, P<0.05). Conclusions:Compared to systemic therapy alone, both radical and palliative surgery plus systemic therapy can improve the pro-gnosis of patients with initially resectable GCLM. The larger primary gastric tumor, poorly differen-tiated tumor, larger liver metastasis, multiple hepatic metastases are independent risk factors for prognosis of patients with initial resectable GCLM and immunotherapy or targeted therapy, the treatment modality of radical or palliative surgery plus systemic therapy are independent protective factors for prognosis of patients with initially resectable GCLM.

Objective:To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM).Methods:This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging ( M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results:(1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95% CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference ( P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options ( HR=1.98, 95% CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients′ prognosis ( HR=2.01, 95% CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors ( HR=2.84, 95% CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver ( HR=2.06, 95% CI 1.19 to 3.57, P=0.010). Conclusions:In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.

Objective:To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM).Methods:This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging ( M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results:(1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95% CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference ( P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options ( HR=1.98, 95% CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients′ prognosis ( HR=2.01, 95% CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors ( HR=2.84, 95% CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver ( HR=2.06, 95% CI 1.19 to 3.57, P=0.010). Conclusions:In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.

Background::Although some well-established oncogenes are involved in cancer initiation and progression such as prostate cancer (PCa), the long tail of cancer genes remains to be defined. Goosecoid ( GSC) has been implicated in cancer development. However, the comprehensive biological role of GSC in pan-cancer, specifically in PCa, remains unexplored. The aim of this study was to investigate the role of GSC in PCa development. Methods::We performed a systematic bioinformatics exploration of GSC using datasets from The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Omnibus, German Cancer Research Center, and our in-house cohorts. First, we evaluated the expression of GSC and its association with patient prognosis, and identified GSC-relevant genetic alterations in cancers. Further, we focused on the clinical characterization and prognostic analysis of GSC in PCa. To understand the transcriptional regulation of GSC by E2F transcription factor 1 ( E2F1), we performed chromatin immunoprecipitation quantitative polymerase chain reaction (qPCR). Functional experiments were conducted to validate the effect of GSC on the tumor cellular phenotype and sensitivity to trametinib. Results::GSC expression was elevated in various tumors and significantly correlated with patient prognosis. The alterations of GSC contribute to the progression of various tumors especially in PCa. Patients with PCa and high GSC expression exhibited worse progression-free survival and biochemical recurrence outcomes. Further, GSC upregulation in patients with PCa was mostly accompanied with higher Gleason score, advanced tumor stage, lymph node metastasis, and elevated prostate-specific antigen (PSA) levels. Mechanistically, the transcription factor, E2F1, stimulates GSC by binding to its promoter region. Detailed experiments further demonstrated that GSC acted as an oncogene and influenced the response of PCa cells to trametinib treatment. Conclusions::GSC was highly overexpressed and strongly correlated with patient prognosis in PCa. We found that GSC, regulated by E2F1, acted as an oncogene and impeded the therapeutic efficacy of trametinib in PCa.

Objective To investigate the clinical efficacy of laparoscopic-assisted linea alba reconstruction for postpartum diastasis recti.Methods The retrospective cross-sectional study was conducted.The clinical data of 14 patients with postpartum diastasis recti who were admitted to Ruijin Hospital of Shanghai Jiaotong University School of Medicine between June 2016 and June 2018 were collected.Patients underwent laparoscopic-assisted linea alba reconstruction.Observation indicators:(1) intra-and post-operative recovery situations;(2) follow-up.Follow-up using outpatient examination and telephone interview was performed to detect postoperative long-term complications,diastasis recti and umbilical hernia recurrence up to September 2018.Measurement data with normal distribution were represented as (x)±s and measurement data with skewed distribution were described as M (P25,P75).Results (1) Intra-and post-operative situations:14 patients underwent successful laparoscopic-assisted linea alba reconstruction and 8 complicated with umbilical hernia area of (6± 3) cm2 were sutured and closed.The mesh area,operation time,visual analogue score for pain at the first day after operation,time of postoperative drainage-tube removal and duration of postoperative hospital stay were respectively (214±26) cm2,(74 ± 14) minutes,3.7 ± 0.6,(3.3 ± 0.7) days and (4.1 ± 1.2) days.No patient required administration of analgesics and had postoperative complication.(2) Follow-up:14 patients were followed up for 17 months (5 months,21 months).During the follow-up,1 patient returned visit at postoperative day 10 due to surgical incision drainage and cured after dressing change.The other patients had no complications,without diastasis recti and umbilical hernia recurrence.Conclusion Laparoscopic-assisted linea alba reconstruction for postpartum diastasis recti is safe and effective.