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Purpose Portal hypertension due to cirrhosis is common among patients with hepatocellular carcinoma (HCC). This study aimed to compare the outcomes of partial hepatectomy in patients with HCC and clinically significant portal hypertension (CSPH) with or without concurrent splenectomy and esophagogastric devascularization (CSED). Patients and methods From a multicenter database, patients with HCC and CSPH who underwent curative-intent hepatectomy were identified. Postoperative morbidity and mortality, and long-term overall survival (OS) were compared in patients with and without CSED before and after propensity score matching (PSM). Results Of the 358 enrolled patients, 86 patients underwent CSED. Before PSM, the postoperative 30-day morbidity and mortality rates were comparable between the CSED and non-CSED group (both P > 0.05). Using PSM, 81 pairs of patients were created. In the PSM cohort, the 5-year OS rate of the CSED group were significantly better than the non-CSED group (52.9%vs.36.5%, P=0.046). The former group had a significantly lower rate of variceal bleeding on follow-up (7.4%vs.21.7%, P=0.014). On multivariate analysis, CSED was associated with significantly better OS (HR: 0.39, P Conclusion Hepatectomy and CSED can safely be performed in selected patients with HCC and CSPH, which could improve postoperative prognosis by preventing variceal bleeding, and prolonging long-term survival.

Background Hepatocellular carcinoma (HCC) is common among adolescents and young adults (AYAs) in areas with endemic hepatitis B virus infection. We sought to characterize clinical features and long-term outcomes among AYAs versus older adults (OAs) who underwent HCC resection. Methods From a Chinese multicenter database, patients were categorized as AYA (aged 13–39 years) versus OA (aged ≥40 years). Patient clinical features, perioperative outcomes, overall survival (OS) and time-to-recurrence (TTR) were compared. Multivariable Cox-regression analyses were performed to identify the impact of age on OS and TTR. Results Among 1952 patients, 354(22.2%) were AYAs. AYAs were less likely to have cirrhosis yet were likely to have advanced tumor pathological characteristics than OAs. Postoperative morbidity and mortality were comparable. Compared with OAs, AYAs had a comparable OS but a decreased TTR. Multivariable analyses identified that young age ( Conclusions Compared with OAs, AYAs had a higher incidence of recurrence following liver resection among patients with HCC, suggesting that enhanced surveillance for postoperative recurrence may be required among AYAs.

To evaluate the health-related quality of life (HRQoL) of knee osteoarthritis (KOA) patients in China, compare their HRQoL with norm population, and examine the associations between the potential influencing factors and HRQoL. A cross-sectional study was conducted in 912 KOA patients from 4 provinces between March and November 2017. All participants were diagnosed according to the National Institute for Health and Care Excellence (NICE)’s criterion or the Chinese Medical Association (CMA)’s criterion. Recruited patients were surveyed for HRQoL using the 12-item Short Form (SF-12) and sociodemographic, disease-related factors. We assessed the associations between potential influencing factors and HRQoL using multiple linear regression models. Among the KOA patients, the mean physical component summary (PCS) of HRQoL was 40.91 ± 11.62, lower than norm (P

Dry eye syndrome (DES) is a common ophthalmological disease that decreases tear secretion and causes dryness, photophobia, pain, severe corneal rupture, and even blindness. Ocular and lacrimal gland inflammation is one of the pathological mechanisms underlying DES. Therefore, effective suppression of inflammation is a crucial strategy for the treatment of DES. Lutein, commonly found in healthy foods, has anti-inflammatory effects in corneal or retina-related cells and may be a potential therapy for DES. The addition of lutein to artificial tears (AT) as an eye-drop formulation for DES treatment in a mouse model was studied in the present work. Polyvinyl alcohol (PVA) was used as a thickener to increase the viscosity of eye drops to prolong drug retention on the ocular surface. A WST-8 assay in human corneal epithelial cells (HCE-2) showed that a concentration of &lt, 5 μM lutein (L5) and &lt, 1% PVA (P1) maintained the cell viability at 80%. A real-time PCR showed that the inflamed human corneal epithelial cells (HCECs) cocultured with L5P1 had downregulated expression of inflammatory genes such as IL-1β, IL-6, and TNF-α. In a benzalkonium chloride- (BAC) induced DES mouse model, AT/L5P1 could repair damaged corneas, elevate tear secretion, increase the number of goblet cells, and inhibit the production of inflammatory cytokines, such as IL-1β, IL-6, and TNF-α, in the cornea. In conclusion, we demonstrate that lutein/PVA as eye drops could prolong the drug ocular retention time and effectively to decrease inflammation in DES mice. Therefore, lutein, obtained from eye drops, has a potential therapeutic role for DES.

BackgroundImmune checkpoint inhibitors (ICIs) have dramatically altered the treatment landscape for patients with melanoma. However, their use also generates unique immune-related adverse effects (irAEs). We performed a systematic review and network meta‐analysis to compare the risk of pneumonitis associated with ICIs for patients with advanced or metastatic melanoma.MethodsPhase II/III randomized clinical trials (RCTs) with ICIs were identified through comprehensive searches of multiple databases. An NMA was conducted to compare the risk of pneumonitis associated with ICIs and all‐grade (grade 1‐5) and high‐grade (grade 3‐5) immune‐related pneumonitis (IRP) were estimated by odds ratios (ORs).ResultsA total of 10 randomized clinical trials involving 5,335 patients were enrolled in this study. Conventional chemotherapy was associated with a lower risk of grade 1–5 IRP compared with ICIs monotherapy (OR, 0.14, 95% CI, 0.03 to 0.73) and dual ICIs combination (OR, 0.03, 95% CI, 0.00 to 0.19). In addition, dual ICIs combination showed a noticeably higher risk than ICI monotherapy (OR, 4.45, 95% CI, 2.14 to 9.25) of grade 1–5 IRP. No significant difference in grade 1–5 IRP was observed between cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) inhibitors. As to grade 3‐5 IRP, no statistically significant difference was found among different ICIs-based regimens.ConclusionThese findings revealed that ICIs could increase the risk of all-grade pneumonitis for patients with advanced melanoma, compared with conventional chemotherapy. Dual ICIs combination could further increase the risk of all-grade pneumonitis than ICIs monotherapy. There was no significant difference in the risk of pneumonia between CTLA-4 and PD-1 inhibitors.

Background: To estimate the transition probabilities of esophageal cancer（EC） and its precancerous lesions by Markov model, which could provide important information for EC screening about choosing reasonable screening and follow-up intervals.Methods: The transition probabilities among pathological stages were estimated by establishing Markov models for the natural history of EC and repeatedly adjusting and calibrating Markov models by comparing the modeled incidence and distributions of pathological stages (alone or combined) with observed data in real-world condition. Results: In one year, the probabilities were 0.024, 0.05, 0.12 for people from health state progressing to mild dysplasia (mD), mild dysplasia (mD) to moderate dysplasia (MD), and moderate dysplasia (MD) to severe dysplasia/carcinoma in situ (SD/CIS), respectively. The age-specific transition probabilities were 0.08~0.18 for severe dysplasia/carcinoma in situ (SD/CIS) progressing to intramucosal carcinoma(IC), 0.4~0.87 for intramucosal carcinoma (IC) to submucosal carcinoma (T1N0M0) (SC), and 0.2~0.85 for submucosal carcinoma (T1N0M0) (SC) to invasive carcinoma (INC). The progression probabilities increased with age and the severity of the disease. Based on the estimated transition probabilities, we predicted the incidence of EC and distributions of its pathological stages. Comparisons between modeled results with observed data confirmed the validation of our transition probabilities.Conclusions: An esophageal cancer transition model in high-risk areas of China has been established with validity. It could be a point of reference for further economic evaluation and policy formulation of esophageal cancer screening.

PurposeTo characterize clinical features and identify baseline prognostic factors for survival in young adults with advanced gastric cancer (YAAGC).Materials and MethodsA total of 220 young inpatients (age less than or equal to 40 years) with an initial diagnosis of advanced gastric cancer were retrospectively enrolled in this study.ResultsOf a consecutive cohort of 220 patients with YAAGC, the median overall survival (OS) time was 16.3 months. One-year survival rate was 43.6% (95% CI: 36.5 to 50.7). In this cohort, a female (71.4%, n = 157) predominance and a number of patients with poorly differentiated tumors (95.9%, n = 211) were observed. In the univariate analysis, OS was significantly associated with neutrophil–lymphocyte ratio (NLR) (≥3.12), hypoproteinemia (p = 0.015] and high NLR level (HR 1.446, 95% CI 1.022 to 2.047, p = 0.021) were two independent poor prognostic factors, while previous radical gastrectomy was associated with a favorable OS (HR 0.345, 95% CI 0.205 to 0.583, p = 0.000). A three-tier prognostic index was constructed dividing patients into good-, intermediate-, or poor-risk groups. Median OS for good-, intermediate-, and poor-risk groups was 36.43, 17.87, and 11.27 months, respectively.ConclusionsThree prognostic factors were identified, and a three-tier prognostic index was devised. The reported prognostic index may aid clinical decision-making, patient risk stratification, and planning of future clinical studies on YAAGC.

BackgroundHepatocellular carcinoma (HCC) is one of the most serious consequences of chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. This study sought to investigate long-term outcomes after liver resection for HCC among patients with HBV/HCV co-infection (HBV/HCV-HCC) compared with patients with HBV infection (HBV-HCC).MethodsPatients who underwent curative-intent liver resection for HCC were identified from a multicenter Chinese database. Using propensity score matching (PSM), patients with HBV/HCV-HCC were matched one-to-one to patients with HBV-HCC. Overall survival (OS) and recurrence-free survival (RFS) were compared between the two groups before and after PSM.ResultsAmong 2,467 patients identified, 93 (3.8%) and 2,374 (96.2%) patients had HBV/HCV-HCC and HBV-HCC, respectively. Compared with patients with HBV-HCC, patients with HBV/HCV-HCC were older, have poorer liver-related characteristics but better tumor-related characteristics. PSM created 88 pairs of patients with comparable liver- and tumor-related characteristics (all P > 0.2). In the PSM cohort, the 3- and 5-year RFS rates in patients with HBV/HCV-HCC were 48.3% and 38.9%, which were significantly poorer than patients with HBV-HCC (61.8% and 49.2%, P = 0.037). Meanwhile, the 3- and 5-year OS rates in patients with HBV/HCV-HCC were also poorer than patients with HBV-HCC (65.4% and 51.1% vs. 73.7% and 63.0%), with a difference close to be significant between them (P = 0.081).ConclusionComparing to patients with HBV-HCC, liver resection resulted in relatively poorer long-term surgical outcomes in patients with HBV/HCV-HCC.

Background: Early identification of bipolar disorder (BD) from major depressive disorder (MDD) is difficult since no tools available to estimate the risk of BD. This study aimed to develop and validate a model of oxidative stress injury for predicting BD. Methods: Data of 1,252 BD and 1,359 MDD patients were collected, including 64 MDD patients who were identified as converting to BD from 2009 through 2018. 30 variables from a randomly selected subsample of 1,827 (70%) patients were used to develop the model, including age, sex, oxidative stress markers (uric acid, bilirubin, albumin, prealbumin), sex hormones, cytokines, thyroid and liver function, glycolipid metabolism, etc. Univariate analyses and the Least Absolute Shrinkage and Selection Operator (LASSO) were applied for data dimension reduction and variable selection. Multivariable logistic regression was used to construct BIOS model on nomogram. Internal validation assessed in the remaining 784 patients (30%), and independent external validation done by 3,797 matched patients from five other hospitals in China. Results: 10 predictors, mainly the oxidative stress markers, were shown on nomogram. BIOS model showed good discrimination in the training sample, with AUC of 75.1% (95% CI: 72.9%~77.3%), sensitivity of 0.66, and specificity of 0.73. The discrimination was well both at internal validation (AUC 72.1%, 68.6~75.6%) and external validation (AUC 65.7%, 63.9~67.5%). Conclusion: A nomogram centered on oxidative stress injury could help individualized prediction of BD. For better real-world practice, a set of measurements especially on oxidative stress markers should be emphasized using big data in psychiatry. Funding: China Key R&D Program (2016YFC1307100), the NSFC (81930033, 81771465, 91232719), SMHC-CRC (CRC2018DSJ01-1), and the Innovative Research Team of High-level Local Universities in Shanghai. Declaration of Interest: None to declare. Ethical Approval: The study was registered at International Clinical Trials Registry Platform with the number of NCT03949218. Ethical issue was approved by the SMHC Institution Review Board (IRB, number of 2019-15R) and the informed consent requirement was omitted according to relevant research.

Background: To estimate the transition probabilities of esophageal cancer (EC) and its precancerous lesions during the process of canceration by Markov model, which could provide important information for EC screening with regard to choosing reasonable screening and follow-up intervals.Methods: The transition probabilities among pathological stages were estimated by establishing Markov models for the natural history of EC and repeatedly adjusting and calibrating Markov models through comparing the modeled incidence and distributions of pathological stages (alone or combined) with observed data in real world condition. Results: In one year, the probabilities were 0.024, 0.05, 0.12 for people from health state progressing to mild dysplasia (mD), mild dysplasia (mD) to moderate dysplasia (MD), and moderate dysplasia (MD) to severe dysplasia/carcinoma in situ (SD/CIS), respectively. The age-specific transition probabilities were 0.08~0.18 for severe dysplasia/carcinoma in situ (SD/CIS) progressing to intramucosal carcinoma(IC), 0.4~0.87 for intramucosal carcinoma (IC) to submucosal carcinoma (T1N0M0) (SC), and 0.2~0.85 for submucosal carcinoma (T1N0M0) (SC) to invasive carcinoma (INC). The progression probabilities increased with age and the severity of the disease. Based on the estimated transition probabilities, we predicted the incidence of EC and distributions of its pathological stages. Comparisons between modeled results with observed data confirmed the validation of our transition probabilities.Conclusion: The estimating transition probabilities of EC and its precancerous lesions were reliable and could be used to address questions such as the optimal screening frequency, screening intervals, and health economic evaluation of screening strategies.

Background Body mass index (BMI) has been widely used as a prognostic indicator. The association between preoperative BMI and postoperative morbidity in patients with hilar cholangiocarcinoma (HCCA) has not been proved. This study aimed to identify the association between preoperative BMI and postoperative morbidity following radical resection of HCCA. Methods Patients were divided into three groups according to preoperative BMI: low BMI (≤18.4 kg/m2 ), normal BMI (18.4-24.9 kg/m2 ), and high BMI (≥24.9 kg/m2 ). Baseline characteristics, operative variables, postoperative 30-day mortality, and morbidity were compared. Risk factors associated with postoperative morbidity were assessed using univariable and multivariable logistic analyses. Results Among 260 patients, 183 (70.4%) had normal BMI, 32 (12.3%) had low BMI, and 45 (17.3%) had high BMI. Compared to the patients with normal-BMI, both low and high BMI patients exhibited a significantly higher postoperative morbidity (87.5% and 82.2% vs 63.9%, P = .019 and P = .025, respectively). Additionally, the multivariable analysis revealed that both low and high BMI patients remained independently associated with an increased risk of postoperative morbidity. (OR: 3.707, 95% CI: 1.080-12.725, P = .037; and OR: 2.858, 95% CI: 1.167-7.002, P = .022, respectively). Conclusion BMI is an independent risk factor for higher postoperative morbidity in patients who undergo surgical treatment of hilar cholangiocarcinoma.

Background: Bipolar disorder (BD) is a kind of mental disorder with the greatest risk of suicide, but it is often misdiagnosed as major depressive disorder (MDD) clinically. This study aimed to analyze the sociodemographic factors and clinical characteristics associated with suicide attempts (SA) in patients with BD misdiagnosed with MDD in China. Methods: A total of 1487 MDD patients were consecutively enrolled in 13 mental health centers in China. Data on patients’ sociodemographic and clinical characteristics were collected using a standardized protocol. Of these, 306 BD patients were misdiagnosed with MDD according to the Mini International Neuropsychiatric Interview (MINI). Suicide attempters and non-attempters were classified by the suicidality module of the MINI. Multiple logistic regression analyses were performed to assess the association between the independent variables of interest and SA in BD patients misdiagnosed with MDD. Results: Of the 306 BD patients misdiagnosed with MDD, 225 (73.5%) were non-attempters and 81 (26.5%) were attempters. Compared to non-attempters, attempters were older (Z =2.2, p = 0.03) and had more admissions(χ2 =6.1, p = 0.013), more frequent depressive episodes, more atypical characteristics (e.g. increased appetite, weight gain, and more sleep time)(χ2 = 5.8, p = 0.016), more suicidal ideation (χ2 = 27.3, p < 0.001), more psychotic symptoms (χ2 = 7.4, p = 0.006) and more seasonal depressive episodes (χ2 = 5.6, p = 0.018). Multiple logistic regression analyses revealed that attempters were characterized by more suicidal ideation (OR = 5.7, 95% CI: 2.6–12.5) and frequent depressive episodes (OR = 2.4, 95% CI: 1.3–4.6). The limitations of this study include its cross-sectional design and data collection by suicide attempters’ retrospective recall. Conclusions: The findings of this study suggest that BD patients misdiagnosed with MDD are at a higher risk of suicide, and more frequent depressive episodes and suicidal ideation are risk factors for attempted suicide. Early identification of and interventions for these risk factors might reduce the risk of suicide in BD patients misdiagnosed with MDD.

Preoperative serum carbohydrate antigen 125 (CA125) is used to judge the diagnosis and prognosis of various tumors. However, the relationship between preoperative serum CA125 and prognosis of hilar cholangiocarcinoma (HCCA) has not been proven. This study aims to evaluate preoperative serum CA125 in predicting the prognosis of HCCA after resection.A total of 233 patients after radical resection of HCCA were included. The associations between the levels of preoperative serum CA125 and the clinicopathological characteristics of patients were analyzed. Survival curves were calculated using the Kaplan-Meier method. Univariate and multivariate Cox regression models were used to identify independent risk factors associated with recurrence-free survival (RFS) and overall survival (OS).Among 233 patients, 198 (84.97%) with normal CA125 levels (≤35 U/mL) had better OS and RFS than 35 (15.02%) patients with higher CA125 levels (35 U/mL). Preoperative serum CA125 was significantly correlated with tumor size, Bismuth-Corlette classification, microvascular invasion and carcinoembryonic antigen (CEA) (p 0.001, p = 0.040, p = 0.019 and p = 0.042, respectively). The results of multivariable Cox regression showed that preoperative serum CA12535 U/mL (p = 0.002, HR = 1.910 for OS; p = 0.006, HR = 1.755 for RFS), tumor classification (p 0.001, HR = 2.110 for OS; p = 0.006, HR = 1.730 for RFS), lymph node metastasis (p 0.001, HR = 1.795 for OS; p 0.001, HR = 1.842 for RFS) and major vascular invasion (p = 0.002, HR = 1.639 for OS; p = 0.005, HR = 1.547 for RFS) were independent risk factors for both OS and RFS.Preoperative serum CA125 is a good tumor marker for predicting prognosis after radical surgery for HCCA.

Background Iatrogenic biliary injury (IBI) following laparoscopic cholecystectomy (LC) is the most serious iatrogenic complications. Little is known whether LC-IBI would lead to surgeon's severe mental distress (SMD). Methods A cross-sectional survey in the form of electronic questionnaire was conducted among Chinese general surgeons who have caused LC-IBI. The six collected clinical features relating to mental distress included: 1) feeling burnout, anxiety, or depression, 2) avoiding performing LC, 3) having physical reactions when recalling the incidence, 4) having the urge to quit surgery, 5) taking psychiatric medications, and 6) seeking professional psychological counseling. Univariable and multivariable analyses were performed to identify risk factors of SMD, which was defined as meeting ≥3 of the above-mentioned clinical features. Results Among 1466 surveyed surgeons, 1236 (84.3%) experienced mental distress following LC-IBI, and nearly half (49.7%, 614/1236) had SMD. Multivariable analyses demonstrated that surgeons from non-university affiliated hospitals (OR:1.873), patients who required multiple repair operations (OR:4.075), patients who required hepaticojejunostomy/partial hepatectomy (OR:1.859), existing lawsuit litigation (OR:10.491), existing violent doctor–patient conflicts (OR:4.995), needing surgeons' personal compensation (OR:2.531), and additional administrative punishment by hospitals (OR:2.324) were independent risk factors of surgeon's SMD. Conclusion Four out of five surgeons experienced mental distress following LC-IBI, and nearly half had SMD. Several independent risk factors of SMD were identified, which could help to make strategies to improve surgeons' mental well-being.

Cetuximab (CTX) has been used to treat metastatic colorectal cancer (mCRC) with wild-type (wt) RAS and BRAF genes. Meanwhile HER2 amplification reportedly denoted CTX-resistant mCRC tumors. We investigated whether monitoring of HER2 amplification in circulating DNA allowed early detection of mCRC progression and CTX resistance. We analyzed HER2 amplification in circulating DNA at 8-week intervals using ddPCR from 36 patients with RASwt/BRAFwt mCRC, who progressed after CTX treatments between July 2015 and January 2018. Of the 36 patients, 5 (13.9%) exhibited dynamic fluctuations of HER2 amplification in plasma in the course of CTX treatment, of whom 2 were positive for HER2 amplification in matched tumor specimens at baseline (per FISH). All 5 primary sites were left side: 3 rectums and 2 descending colon. HER2 ratio fluctuations in circulating DNA not only reflected changes in tumor volume, but their obvious increases presaged CT-documented progress by an average lead time of 2 months. Interestingly, progression-free survival did not significantly differ between these 5 patients and those without HER2 amplification (HR 1.06, 95% CI 0.40–2.77, P = 0.909). Plasma HER2 amplification detected by ddPCR changed over time and predicted resistance to CTX, by an average lead time of 2 months. Further study is needed to validate our findings.

OBJECTIVE To analyze the sociodemographic and clinical factors related to anxiety in patients with major depressive disorder (MDD). METHODS This study involved a secondary analysis of data obtained from the Diagnostic Assessment Service for People with Bipolar Disorders in China (DASP), which was initiated by the Chinese Society of Psychiatry (CSP) and conducted from September 1, 2010 to February 28, 2011. Based on the presence or absence of anxiety-related characteristics, 1,178 MDD patients were classified as suffering from anxious depression (n=915) or non-anxious depression (n=263), respectively. RESULTS Compared with the non-anxious group, the anxious-depression group had an older age at onset (t=-4.39, p

Little is known about the demographic and clinical features of the atypical subtype of major depressive disorder (MDD) patients in China. This study set out to investigate the prevalence of atypical depression in MDD patients in China, and identify its demographic and clinical features.The study was conducted in 13 major psychiatric hospitals or in the psychiatric units of general hospitals in China, and recruited a sample of 1172 patients diagnosed with MDD. The patients' demographic and clinical features and prescriptions of psychotropic drugs were collected using a standardized questionnaire designed for the study.The prevalence of atypical depression was 15.3%. In multiple logistic regression analyses, compared to the non-atypical depression patients, the atypical depression patients were more likely to have depressive episodes with suicide ideation and attempts (OR = 1.49, 95% CI = 1.06, 2.10, P = 0.023), depressive episodes with psychotic features (OR = 2.15, 95% CI = 1.43, 3.22, P 0.001), seasonal depressive episodes (OR = 1.77, 95% CI = 1.12, 2.78, P = 0.014), an earlier age of onset (OR = 0.98, 95% CI = 0.96, 0.99, P = 0.001), and lifetime depressive episodes (OR = 1.07, 95% CI = 1.01, 1.13, P = 0.020).The assessment of atypical features was not based on a validated rating scale.Our results indicate that atypical depression is common in Chinese patients with MDD. MDD with atypical features may be more severe and debilitating than patients with non-atypical features.

AIM Transcutaneous electrical acupoint stimulation (TEAS) has the potential to alleviate post-traumatic stress disorder (PTSD). The purpose of this study was to determine whether adding TEAS to sertraline or cognitive behavioral therapy (CBT) could improve the anti-PTSD efficacy. METHODS In this randomized controlled trial, 240 PTSD patients (60 in each group) were assigned to receive simulated TEAS combined with sertraline (group A) or with CBT (group B), active TEAS combined with CBT (group C), or active TEAS combined with CBT plus sertraline (group D) for 12 weeks. The outcomes were measured using the Clinician-Administered PTSD Scale, PTSD Check List-Civilian Version, and 17-item Hamilton Rating Scale for Depression. RESULTS While PTSD symptoms reduced over time in all patients, groups C and D had markedly greater improvement in both PTSD and depressive measures than groups A and B in all post-baseline measurement points, with moderate to very large effect sizes of 0.484-2.244. Groups C and D also had a significantly higher rate than groups A and B on clinical response (85.0% and 95.0% vs 63.3% and 60.0%, P

Objective: To analyze the factors associated with recent suicide attempts including socio-demographic and clinical characteristics in major depressive disorder (MDD) patients in China.Methods: The data were from a nationwide sample from 13 major psychiatric hospitals or the psychiatric units of general hospitals in China, from September 1, 2010 to February 28, 2011. Melancholic features and suicide attempts in the past month were defined according to the melancholic feature module and the suicide module of the Mini International Neuropsychiatric Interview (MINI). Socio-demographic and clinical characteristics were compared between MDD patients with and without recent suicide attempts. Further analyses regarding the factors associated with recent suicide attempts in MDD patients were performed via multivariate logistic regression analysis.Results: Among 1,172 MDD patients, 57 (4.9%) were reported to have made a suicide attempt in the past month. Compared to the MDD patients without recent suicide attempt, significantly higher percentage of patients in the recent suicide attempters group had previous suicide attempts (χ2 = 171.861, p < 0.001) and depressive episodes with melancholic features (χ2 = 22.837, p < 0.001). Logistic regression analysis indicated that previous suicide attempts (OR = 20.81, 95% CI: 11.12–38.94, p < 0.001) and depressive episodes with melancholic features (OR = 4.43, 95% CI: 2.09–9.43, p < 0.001) were independently associated with recent suicide attempts in MDD patients.Limitations: Cross-sectional design, retrospective recall of suicide attempt data.Conclusion: Recent suicide attempts are associated with melancholic features and previous suicide attempts in MDD patients in China. These data may help clinicians to identify MDD patients at high risk of suicide attempt behavior.

Background and Purpose Glucokinase (GK) balances blood glucose levels via regulation of glucose metabolism and insulin secretion. Peroxisome proliferator activated receptor-γ (PPARγ) regulates gene expression in glucose and lipid metabolism. In this study, we investigated the therapeutic effect of a novel compound, SHP289-03, which activates both GK and PPARγ. Methods Glucose metabolism was tested in primary hepatocytes of normal ICR mice, and insulin secretion was measured in NIT-1 insulinoma cells as well as in primary islets of normal ICR mice. The in vivo pharmacodynamics of SHP289-03 was assessed using the spontaneous type 2 diabetic mouse model, KKA y . Key Results In hepatocytes, SHP289-03 promoted glucose consumption. In NIT-1 cells, it increased the concentration of intracellular ATP and calcium, and subsequently enhanced glucose-stimulated insulin secretion in both NIT-1 cells and primary islets. Moreover, SHP289-03 decreased the blood glucose level, improved glucose tolerance and reduced blood lipid levels in KKA y mice. It restored islet morphology and increased the beta cell/alpha cell mass ratio, in addition to up-regulating GK gene expression in the liver of KKA y mice. Discussion and Conclusions SHP289-03 has significant therapeutic potential for the treatment of diabetes mellitus.

We investigated mechanisms of pancreatic cancer metastasis and defined the biological role of miR-29c in pancreatic cancer metastasis. After two rounds of cell selection in vivo, pancreatic cancer cells with various metastatic potentials derived from spontaneous liver metastases were used as a model of pancreatic cancer to determine the role of miR-29c in pancreatic cancer metastasis. Pancreatic cancer samples were analyzed for miRNA-29c expression, and these levels were associated with survival between groups. miR-29c suppresses cell migration and invasion by targeting the MMP2 3'UTR. Overexpression of miR-29c suppresses pancreatic cancer liver metastasis in a nude mouse orthotopic implantation model. miR-29c expression was associated with metastasis and pancreatic cancer patient survival. miR-29c plays an important role in mediating pancreatic cancer metastasis to the liver by targeting MMP2. Therefore, miR-29c may serve as a novel marker of pancreatic cancer metastasis and possibly as a therapeutic target to treat pancreatic cancer liver metastasis.

Background This study investigated suicide risk and its correlates among major affective disorder patients in China and examined possible risk factors for future suicide among individuals with major affective disorder to inform appropriate interventions and management approaches to minimize and prevent suicide. Methods A total of 1478 major affective disorder patients were consecutively examined in 13 mental health centers in China. The patients' socio-demographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. DSM-IV diagnoses were established using the Mini International Neuropsychiatric Interview (MINI), and suicide risk was assessed by the suicide risk module of the MINI. Results Of the patients, 963 (65.2%) were in the nonsuicidal risk group and 515 (34.8%) were in the suicidal risk group. Compared to major depressive disorder patients, bipolar disorder patients had higher suicide risk levels ( χ 2=10.0, df=1, P =0.002); however, there were no statistically significant differences ( χ 2=2.6, df=1, P =0.1) between bipolar disorder-I and bipolar disorder-II patients. Suicide risk factors were associated with 6 variables in major affective disorder patients, as follows: male gender, unemployed, more frequent depressive episodes (>4 in the past year), depressive episodes with suicidal ideation and attempts, depressive episodes with psychotic symptoms, and no current antidepressant use. Limitations Most of the data were retrospectively collected and, therefore, subject to recall bias. Conclusions This study suggested that bipolar disorder patients have a higher suicide risk than major depressive disorder patients. The factors that were significantly associated with suicide risk may aid in identifying major affective disorder patients who are at risk for future suicidal behavior.

BACKGROUND: The aim of this study was to screen for retinopathy of prematurity (ROP) in southwestern China and understand the prevalence and risk factors of ROP, which may provide evidence useful in the prevention and treatment of ROP. MATERIAL/METHODS: 1864 preterm infants (gestational age of

Objectives Bipolar disorder (BD) is frequently misdiagnosed as major depressive disorder (MDD), which may lead to inappropriate treatment and poor outcomes. This study aimed to compare demographic and clinical features between patients with MDD and those with BD, but being misdiagnosed as MDD, in China. Methods A total of 1487 patients diagnosed with MDD were consecutively evaluated in 13 psychiatric hospitals or psychiatric units of general hospitals nationwide in China. The patients' sociodemographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. The Mini-International Neuropsychiatric Interview (MINI) was used to establish DSM-IV diagnoses, and identify patients with MDD and those with BD, but being misdiagnosed with MDD. Results The proportions of BD (all types), bipolar I disorder (BD-I), and bipolar II disorder (BD-II) misdiagnosed as MDD in clinical practice were 20.8%, 7.9%, and 12.8%, respectively. Multiple logistic regression analyses revealed that compared to MDD patients, BD-I was characterized by more atypical depressive features (increased appetite, increased sleep, and weight gain) [odds ratio (OR) = 2.0, 95% confidence interval (CI): 1.2–3.2], more psychotic symptoms (OR = 2.1, 95% CI: 1.3–3.5), more lifetime depressive episodes (OR = 1.1, 95% CI: 1.1–1.2), and earlier age of onset (OR = 0.97, 95% CI: 0.9–0.99); BD-II was characterized by more psychotic symptoms (OR = 2.1, 95% CI: 1.4–3.1) and earlier age of onset (OR = 0.96, 95% CI: 0.9–0.97). In addition, compared to BD-II patients, BD-I patients were characterized by more frequent depressive episodes per year (OR = 3.1, 95% CI: 1.5–6.6). Conclusions Depressive episodes in the context of BD-I and BD-II, among those who were misclassified as MDD, present some different clinical features compared to MDD. This finding should be taken into account in guiding diagnostic practices in China.

Background Bipolar disorder (BD) is often misdiagnosed as a major depressive disorder (MDD). This study aimed to test the usefulness of the screening tool, the Mood Disorders Questionnaire (MDQ), to identify BD patients misdiagnosed as MDD in Chinese clinical settings. Methods A total of 1487 patients treated for MDD were consecutively examined in 13 mental health centers in China. The patients’ socio-demographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. The MDQ was completed by patients to identify symptoms characteristic of BD. DSM-IV diagnoses were established using the Mini International Neuropsychiatric Interview (MINI). Results Three hundred-nine of the 1487 patients (20.8%) satisfied DSM-IV criteria for BD; 118 (7.9%) for BD-I and 191 (12.8%) for BD-II on the MINI. The optimal cut-off point on the MDQ to differentiate BD from MDD was 3, while cut-off points of 5 and 3 differentiated BD-I and BD-II from MDD, respectively. The maximum sensitivity was 0.31, 0.45 and 0.22 for differentiating BD, BD-I and BD-II from MDD, respectively. Conclusions The optimal cutoff points of the MDQ for screening BD in Chinese patients originally diagnosed as MDD were considerably lower than those in earlier studies. The routine clinical use of the MDQ as a screening scale for BD in Chinese patients treated for MDD does not seem to be justified.

Aim To investigate the results of the Hypomania Checklist-32 (HCL-32) administered as a screening instrument in clinical settings to mood disorders patients in the depressive phase. Methods A total of 1487 patients diagnosed and being treated for major depressive disorder (MDD) in 13 mental health centers across China were self-rated by the HCL-32 and independently examined by the Mini International Neuropsychiatric Interview (MINI). Results After examination by the MINI, 309 (20.8%) of the 1487 patients clinically diagnosed as having MDD satisfied DSM-IV criteria for bipolar disorder (BD): 118 (7.9%) for bipolar I disorder (BD-I) and 191 (12.8%) for bipolar II disorder (BD-II). The mean HCL-32 score of the BD patients was statistically higher than that of patients with unipolar depression (UD, major depressive disorder), BD-II higher than UD, while no significant difference between BD-I and BD-II. The HCL-32 distinguished between BD and UD (best cutoff score 14), between BD-II and UD (best cutoff 12). At the optimum cutoff of 12 between BD and UD, the sensitivity was 0.86, specificity 0.69. Limitations No standardized instruments were used to measure the severity of depressive symptoms. Depressed patients with a previous history of BD were excluded from this study. Conclusions The HCL-32 results in this multicenter study of patients in the depressive phase were similar to those of earlier, generally smaller-scale studies which subjects could be in any mood phases. A score of 12 could be used as the optimum cutoff between BD and UD to improve screening for BD-II if the HCL-32 was applied in clinical settings in China.

Application of autologous serum eye drops (SEDs) is a recognized means to treat severe dry-eye syndrome (DES). Due to the inconvenience and difficulty of preparing SEDs from some patients, producing SEDs from allogeneic blood donations is gaining popularity. A major safety concern associated with allogeneic blood is virus transmission. We therefore herein evaluated the possibility of applying a solvent/detergent (S/D) treatment to inactivate viruses and studied the impacts of such treatment of SEDs to resolve DES in a rabbit model. Sera prepared from the blood of five rabbits were pooled and divided into two sub-pools. One was untreated (SEDs), while the other was virally-inactivated with 1% Tri-n-butyl phosphate/1% Triton X-45 at 31°C for 1 h (S/D-SEDs). DES was induced in rabbits using 0.1% benzalkonium chloride (BAC). Rabbits were divided into five groups of two rabbits each. One group was untreated (control), three were treated twice daily for 3 weeks using PBS, SEDs, or S/D-SEDs, and the last received an additional 0.1% BAC (as the negative control). The DES condition was determined by measuring aqueous tear secretion (Schirmer's test), corneal fluorescein staining, a corneal histologic examination, TUNEL stain apoptosis, and corneal inflammatory marker (tumor necrosis factor-α, interleukin (IL)-1β, IL-8, and IL-6) expressions. We first confirmed that SEDs and S/D-SEDs had similar protein profiles and transforming growth factor (TGF)-β contents. Animal experiments showed that tear secretion did not significantly differ between the SED and S/D-SED groups but was significantly higher than in the PBS group. Eye fluorescein staining revealed dramatic improvements in epithelial defects in groups treated with SEDs or S/D-SEDs, and hematoxylin/eosin staining revealed microscopic epithelial layers similar to those of the untreated controls. Inflammatory markers and TUNEL studies showed that healthy epithelium had been restored in groups treated with SEDs or S/D-SEDs. In conclusion, this preclinical study supports the possibility of using S/D virally inactivated SEDs to treat DES and restore a normal epithelium.

Objective Bipolar disorder (BD) is frequently misdiagnosed as major depressive disorder (MDD), which may lead to inappropriate treatment and poor outcomes. This study aimed to examine prescribing patterns of antidepressants, antipsychotics and mood stabilizers in BD patients misdiagnosed with MDD in China. Methods A total of 1487 patients originally diagnosed with MDD were consecutively screened for diagnostic revision in 13 psychiatric hospitals or psychiatric units of general hospitals in China nationwide. The patients' sociodemographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. The Mini International Neuropsychiatric Interview (MINI) was used to establish DSM-IV diagnoses. Data on psychotropic prescriptions were collected by a review of medical records. Results Three hundred and nine of the 1487 patients (20.8%) fulfilled DSM-IV criteria for BD; 118 (7.9%) for BD-I and 191 (12.8%) for BD-II on the MINI. Of the BD patients (n = 309), 227 (73.5%) received any use of antidepressants, 73 (23.6%) antipsychotics and 33 (10.7%) mood stabilizers. In multiple logistic regression analyses, compared with those with MDD, patients with BD-I were more likely to receive antidepressants (OR 1.7, 95% CI 1.1–2.8, p = 0.02), antipsychotics (OR 1.6, 95% CI 1.04–2.5, p = 0.04) and mood stabilizers (OR 3.9, 95% CI 2.1–7.2, p

Background Bipolar disorder (BD) is a recurrent, complex illness and often misdiagnosed and treated as a major depressive disorder (MDD). This study set out (1) to investigate the proportion of BD in patients treated for MDD using DSM-IV diagnostic criteria; (2) to test the usefulness of the screening tool — the 32-item Hypomania Checklist (HCL-32) in Chinese patients; and (3) to assess whether MDD patients with subthreshold manic features (patients who screened positive for BD on the HCL-32, but did not meet the diagnostic criteria for DSM-IV BD as measured by Mini International Neuropsychiatric Interview (MINI)) differ from those with BD, and from those suffering from MDD without manic features in terms of basic demographic and clinical variables. Methods A total of 1487 patients treated for MDD were consecutively examined in 13 mental health centers in China. The patients' socio-demographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. The HCL-32 was self-completed by patients to identify hypomanic symptoms, and the MINI was used by clinicians to establish DSM-IV diagnoses. Results The proportions of undiagnosed BD (all types), BD-I and BD-II were 20.8%, 7.9% and 12.8%, respectively. The HCL-32 had low positive predictive value (0.43). Compared to MDD patients without subthreshold manic features, MDD patients with subthreshold manic features were younger at onset, less likely to be married and had more depressive episodes on a seasonal basis, and more frequent depressive episodes overall. Compared to BD patients, MDD patients with subthreshold manic features had an older age at onset and less frequent depressive episodes and less family history of psychiatric disorders, appetite, weight gain and time spent sleeping, suicide ideation and attempts and psychotic symptoms. Conclusions At least one fifth of Chinese patients treated for MDD may have an undiagnosed BD. The HCL-32 is useful to identify broader subthreshold bipolar features. The findings need to be confirmed by longitudinal studies using more comprehensive, standardized instruments.

Purpose: Interaction between tumor cells and surrounding stromal fibroblast (SF) plays a critical role in tumor growth and invasion. The aim of the study is to determine the role of SF in regulating the invasive behaviors of pancreatic cancer by evaluating the mode of SF activating the urokinase plasminogen activator (uPA)-plasmin-matrix metalloproteinase (MMP)-2 cascade. Experimental Design: The expression patterns of uPA, MMP-2, and uPA receptor (uPAR) in human metastatic pancreatic cancer were analyzed by immunohistochemistry and the roles of SF in activation of the uPA-plasmin-MMP-2 cascade were evaluated by coculturing pancreatic cancer cell lines with SF. Results: uPA expression and fibroblastic uPAR expression were correlated with liver metastasis of human pancreatic cancer. MMP-2 rather than MMP-9 was activated in the metastatic pancreatic cancer. In the in vitro culture system, the coculture of peritumor fibroblasts with metastatic pancreatic cancer BxPc3 cells resulted in activation of MMP-2 and up-regulation of uPAR expression. In this coculture system, the uPA-plasminogen cascade was involved in MMP-2 activation. This activation required a direct interaction between SF and cancer cells. In the coculture system, intergrin α6β1 expression was increased in BxPc3 cells, and blocking the function of integrin α6β1 decreased the activation of uPA and MMP-2. This suggests that interaction between integrins of cancer cells and the uPARs of the SF might be involved in the activation of the uPAR-uPA-MMP-2 cascade. Conclusion: Our results suggest that SF plays a role in promoting pancreatic cancer metastasis via activation of the uPA-plasminogen-MMP-2 cascade.

Dry eye syndrome (DES) is one of the most common types of ocular diseases. There is a major need to treat DES in a simple yet efficient way. Artificial tears (AT) are the most commonly used agents for treating DES, but are not very effective. Herbal extractions of ferulic acid (FA), an anti-oxidant agent, and kaempferol (KM), an anti-inflammatory reagent, were added to buffer solution (BS) to replace ATs for DES treatment. The cytotoxicity and anti-inflammatory effects were examined in vitro by co-culture with human corneal epithelial cells (HCECs) to obtain the optimal concentration of KM and FA for treating HCECs. Physical properties of BS, such as pH value, osmolality, and refractive index were also examined. Then, rabbits with DES were used for therapeutic evaluation. Tear production, corneal damage, and ocular irritation in rabbits’ eyes were examined. The non-toxic concentrations of KM and FA for HCEC cultivation over 3 days were 1 µM and 100 µM, respectively. Live/dead stain results also show non-toxicity of KM and FA for treating HCECs. Lipopolysaccharide-stimulated HCECs in inflammatory conditions treated with 100 µM FA and 1 µM KM (FA100/KM1) showed lower IL-1B, IL-6, IL-8, and TNFα expression when examined by real-time PCR. The BS with FA100/KM1 had neutral pH, and a similar osmolality and refractive index to human tears. Topical delivery of BS + FA100/KM1 showed no irritation to rabbit eyes. The corneal thickness in the BS + FA100/KM1 treated group was comparable to normal eyes. Results of DES rabbits treated with BS + FA100/KM1 showed less corneal epithelial damage and higher tear volume than the normal group. In conclusion, we showed that the combination of FA (100 µM) and KM (1 µM) towards treating inflamed HCECs had an anti-inflammatory effect, and it is effective in treating DES rabbits when BS is added in combination with these two herbal supplements and used as a topical eye drop.

Background 3-Hydroxy-3-methyl-glutaryl CoA (HMG-CoA) reductase inhibitors or statins are competitive inhibitors of the rate-limiting enzyme in cholesterol biosynthesis. Currently, statins are used as first-line therapy in the treatment of diabetic dyslipidemia. However, effects of statins on β cell function remains unclear. This study aims to examine effects of atorvastatin treatment on pancreatic β cell function in obese C57BL/6 J mice and the possible mechanisms. Methods Diet-induced obesity (DIO) C57BL/6 J mice were treated with atorvastatin (30 mg/kg/day) for 58 days. β cell function was assessed by hyperglycemic clamp and the area of insulin-positive β cells was examined by immunofluorescence. Gene expression was assessed by RT-PCR, and endoplasmic reticulum (ER) stress related proteins were examined by Western blot. Additionally, cell viability and apoptosis of the cholesterol-loaded NIT-1 cells were investigated after atorvastatin treatment. Results Hyperglycemic clamp study revealed that glucose infusion rate (GIR) and insulin stimulation ratio in atorvastatin-treated DIO mice were markedly higher than control mice (P

Background The aim of this study was to test the ability of the Chinese version of the Mood Disorder Questionnaire (MDQ) to identify Bipolar Disorders (BD) in patients diagnosed with Major Depressive Disorder (MDD) or Unipolar Disorder (UD) in the clinical setting. Methods 1,487 being treated for MDD or UD at 12 mental health centers across China, completed the MDQ and subsequently examined by the Mini International Neuropsychiatric Interview (MINI). Receiver Operating Characteristic(ROC) curves were used to determine the ability of the MDQ to differentiate between BD (BD, BD-I and BD-II) and MDD or UD and patients with BD-I from patients with BD-II. Results Of the 1,487 patients, 309 (20.8%) satisfied the DSM-IV criteria for BD: 118 (7.9%) for BD-I and 191 (12.8%) for BD-II. When only part one of the MDQ was used, the best cutoff was 7 between BD and UD (sensitivity 0.66, specificity 0.88, positive predictive value 0.59, negative predictive value 0.91), 6 between BD-II and UD, and 10 between BD-I and BD-II. If all three parts of the MDQ were used, the MDQ could not distinguish between BD and UD at a cutoff of 7 (or 6), and the sensitivity was only 0.22 (or 0.24). Conclusion The Chinese version of the MDQ had good psychometric features in screening bipolar disorders from depressive patients with mood disorders when part two and part three of the MDQ were ignored.

Introduction Little has been reported about the demographic and clinical features of major depressive disorder (MDD) with comorbid dysthymia in Chinese patients. This study examined the frequency of comorbid dysthymia in Chinese MDD patients together with the demographic and clinical correlates and prescribing patterns of psychotropic drugs. Methods Consecutively collected sample of 1178 patients with MDD were examined in 13 major psychiatric hospitals in China. Patients' demographic and clinical characteristics and psychotropic drugs prescriptions were recorded using a standardized protocol and data collection procedure. The diagnosis of dysthymia was established using the Mini International Neuropsychiatric Interview. Medications ascertained included antidepressants, antipsychotics, benzodiazepines, and mood stabilizers. Results One hundred and three (8.7%) patients fulfilled criteria for dysthymia. In multiple logistic regression analyses, compared to non-dysthymia counterparts, MDD patients with dysthymia had more depressive episodes with atypical features including increased appetite, sleep, and weight gain, more frequent lifetime depressive episodes, and less likelihood of family history of psychiatric disorders. There was no significant difference in the pattern of psychotropic prescription between the 2 groups. Conclusions There are important differences in the demographic and clinical features of comorbid dysthymia in Chinese MDD patients compared with previous reports. The clinical profile found in this study has implications for treatment decisions.

BackgroundLittle has been known about the demographic and clinical features of the melancholic subtype of major depressive disorder (MDD) in Chinese patients. This study examined the frequency of melancholia in Chinese MDD patients and explored its demographic and clinical correlates and prescribing patterns of psychotropic drugs.MethodsA consecutively collected sample of 1,178 patients with MDD were examined in 13 psychiatric hospitals or psychiatric units of general hospitals in China nationwide. The cross-sectional data of patients' demographic and clinical characteristics and prescriptions of psychotropic drugs were recorded using a standardized protocol and data collection procedure. The diagnosis of the melancholic subtype was established using the Mini International Neuropsychiatric Interview (MINI). Medications ascertained included antidepressants, mood stabilizers, antipsychotics and benzodiazepines.ResultsSix hundred and twenty nine (53.4%) of the 1,178 patients fulfilled criteria for melancholia. In multiple logistic regression analyses, compared to non-melancholic counterparts, melancholic MDD patients were more likely to be male and receive benzodiazepines, had more frequent suicide ideations and attempts and seasonal depressive episodes, while they were less likely to be employed and receive antidepressants and had less family history of psychiatric disorders and lifetime depressive episodes.ConclusionsThe demographic and clinical features of melancholic MDD in Chinese patients were not entirely consistent with those found in Western populations. Compared to non-melancholic MDD patients, melancholic patients presented with different demographic and clinical features, which have implications for treatment decisions.

Glutathione S-transferase M1 (GSTM1), which plays an important role in detoxification pathways to protect against damage caused by reactive metabolites of chemicals, has been considered as potential gastric cancer susceptibility genes. However, the published data on the association between GSTM1 present/null polymorphism and gastric cancer risk are still inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Totally, 44 studies including 5440 cases and 11607 controls were involved in the analysis. When all studies were pooled into the meta-analysis, obviously increased gastric cancer risk was found in null genotype carriers (OR = 1.19, 95% CI: 1.08–1.33). When stratified by ethnicity, obviously evaluated risk was found in Asians (OR = 1.31, 95% CI: 1.11–1.54) but not reached to statistically significance in Caucasians (OR = 1.11, 95% CI: 0.96–1.28). In the subgroup analysis by hospital-based studies or population-based studies, statistically significantly elevated risk was found in hospital-based studies (OR = 1.34, 95% CI: 1.07–1.67) but not reached to statistically significance in population-based studies (OR = 1.11, 95% CI: 0.99–1.25). In summary, this meta-analysis result indicates that the GSTM1 null genotype is a low-penetrant risk factor for gastric cancer development in Asians.

This study tested the potential of small interfering RNAs (siRNA) targeting human peroxisome proliferator activated receptor gamma (PPARγ) to repress the adipogenic effect of alcohol on human bone marrow-derived mesenchymal cells (hBMSCs). hBMSCs were cultured from hip replacement surgery patients (n = 10). PPARγ-siRNA was transiently transfected into hBMSCs cultured in ostogenic media containing 50 mM alcohol by using a liposome-based strategy. Oil red O staining was used to test the development of differentiated adipocytes, and Alizarin red staining was used to test mineral deposition. Marker genes of adipogenesis (PPARγ2 and aP2) and osteogenesis (Osf2/Cbfa1) were examined through real time RT-PCR and Western blot, respectively. Collagen type I, alkaline phosphatase and osteocalcin protein synthesis of cultures were also assayed. Data were presented as mean ± SD. Differences between the means of the treatment groups were determined with ANOVA. PPARγ-siRNA transfection resulted in significantly lower adipocyte number, increased matrix mineralisation, repressed adipogenic gene markers, up-regulated osteogenic gene marker and bone matrix protein synthesis in the PPARγ-siRNA group compared to controls (P < 0.05). PPARγ-siRNA is a useful strategy to inhibit the adipogenic effect and the osteogenic repression of alcohol on hBMSCs. This may be a novel therapeutic intervention for osteopenic disorders in alcoholism and other conditions.

Interaction of cancer cells with stroma cells facilitates tumor progression by rebuilding the existing extracellular matrix (ECM) microenvironment. In the tumor, upregulation of Tenascin-C (Tn-C) expression potentially can alter tumor behavior. However, the molecular mechanisms by which tumor-stroma interactions affect the tumor microenvironment have not been well characterized. In this study, we analyzed the expression of fibrillar Tn-C (fTn-C) in human metastatic pancreatic cancers. After co-culturing two pancreatic cancer cell lines, highly metastatic BxPc3 cells and non-metastatic PaCa2 cells, with stromal fibroblasts (SF), we evaluated the roles of matrix metalloproteinase 2 (MMP-2) activation and SF in promoting Tn-C organization. Next, we evaluated whether fibrillar Tn-C promotes pancreatic cancer cell movement using cell adhesion and migration assays. Finally, we observed the relationship between MMP-2 activation and fTn-C formation in vivo by injecting the BxPc3 and PaCa2 cells into nude mice. We found that fTn-C was increased in metastatic pancreatic cancer. The fTn-C expression correlated with MMP-2 activity. In the in vitro co-culture, fTn-C organization was found only in BxPc3/SF co-cultures, and required the participation of active MMP-2. The fTn-C reduced cell adhesion and promote pancreatic cancer cell migration by decreasing the adhesive interactions between integrin alpha6beta1 and the ECM. The in vivo tumorigenesis analysis showed that the fTn-C formation and active MMP-2 were significantly increased in the BxPc3 tumors, compared to the PaCa2 tumors. These results demonstrate that Tn-C deposition into the ECM requires participation of active MMP-2 and SF. The deposited Tn-C could promote pancreatic cancer progression.

Burkitt’s lymphoma is an aggressive B-cell lymphoma with rapid proliferative index, which makes it disseminate easily to distal sites, especially to bone marrow and the central nerve system. We report here a 22-year-old woman with Burkitt’s lymphoma involving multiple organs, including kidneys, breasts, left ovary, and bone marrow at the time of diagnosis. The patient responded well to intensive chemotherapy before the onset of retro-orbital pain, vomiting, and photophobia. The contrast-enhanced T1-weighted image in a second magnetic resonance image (MRI) showed a 2 × 1.9 cm mass in her left cavernous sinus that was not found in her initial MRI. Central nervous system (CNS)-directed high-dose chemotherapy and whole-brain radiation could not change the final failed treatment outcome caused by the cavernous sinus involvement disseminating to her entire CNS. Further study should provide well-designed therapeutic strategies to Burkitt’s patients with cavernous sinus involvement.