MP-13, a novel chimeric peptide of morphiceptin and pepcan-9, produces potent antinociception with limited side effects.

Pharmacological investigations have substantiated the potential of bifunctional opioid/cannabinoid agonists in delivering potent analgesia while minimizing adverse reactions. Peptide modulators of cannabinoid receptors, known as pepcans, have been investigated before. In this study, we designed a series of chimeric peptides based on pepcans and morphiceptin (YPFP-NH2). Here, we combined injections of pepcans and morphiceptin to investigate the combination treatment of opioids and cannabis and compared the analgesic effect with chimeric compounds. Subsequently, we employed computational docking to screen the compounds against opioid and cannabinoid receptors, along with an acute pain model, to identify the most promising peptide. Among these peptides, MP-13, a morphiceptin and pepcan-9 (PVNFKLLSH) construct, exhibited superior supraspinal analgesic efficacy in the tail-flick test, with an ED50 value at 1.43 nmol/mouse, outperforming its parent peptides and other chimeric analogs. Additionally, MP-13 displayed potent analgesic activity mediated by mu-opioid receptor (MOR), delta-opioid receptor (DOR), and cannabinoid type 1 (CB1) receptor pathways. Furthermore, MP-13 did not induce psychological dependence and gastrointestinal motility inhibition at the effective analgesic doses, and it maintained non-tolerance-forming antinociception throughout a 7-day treatment regimen, with an unaltered count of microglial cells in the periaqueductal gray region, supporting this observation. Moreover, intracerebroventricular administration of MP-13 demonstrated dose-dependent antinociception in murine models of neuropathic, inflammatory, and visceral pain. Our findings provide promising insights for the development of opioid/cannabinoid peptide agonists, addressing a crucial gap in the field and holding significant potential for future research and development. PERSPECTIVE: This article offers insights into the combination treatment of pepcans with morphiceptin. Among the chimeric peptides, MP-13 exhibited potent analgesic effects in a series of preclinical pain models with a favorable side-effect profile.

Predictors, prevalence and prognostic role of pulmonary hypertension in patients with chronic kidney disease: a systematic review and meta-analysis.

BACKGROUND: To estimate the predictors, prevalence and prognostic role of pulmonary hypertension (PH) in patients with chronic kidney disease (CKD) using meta-analysis. METHODS: The PubMed, EmBase, and the Cochrane library were systematically searched for eligible studies from inception till May 2024. All of pooled analyses were performed using the random-effects model. RESULTS: Fifty observational studies involving 17,558 CKD patients were selected. The prevalence of PH in CKD patients was 38% (95% confidence interval [CI]: 33%-43%), and the prevalence according to CKD status were 31% (95% CI: 20%-42%) for CKD (I-V), 39% (95% CI: 25%-54%) for end stage kidney disease (ESKD) (predialysis), 42% (95% CI: 35%-50%) for ESKD (hemodialysis), and 26% (95% CI: 19%-34%) for renal transplant. We noted the risk factors for PH in CKD included Black individuals (relative risk [RR]: 1.39; 95% CI: 1.18-1.63; p < 0.001), chronic obstructive pulmonary disease (RR: 1.48; 95% CI: 1.21-1.82; p < 0.001), cardiovascular disease history (RR: 1.62; 95% CI: 1.05-2.51; p = 0.030), longer dialysis (RR: 1.70; 95% CI: 1.18-2.46; p = 0.005), diastolic dysfunction (RR: 1.88; 95% CI: 1.38-2.55; p < 0.001), systolic dysfunction (RR: 3.75; 95% CI: 2.88-4.87; p < 0.001), and grade 5 CKD (RR: 5.64; 95% CI: 3.18-9.98; p < 0.001). Moreover, PH in CKD patients is also associated with poor prognosis, including all-cause mortality, major cardiovascular events, and cardiac death. CONCLUSION: This study systematically identified risk factors for PH in CKD patients, and PH were associated with poor prognosis. Therefore, patients with high prevalence of PH should be identified for treatment.

Network analysis of microbiome and metabolome to explore the mechanism of raw rhubarb in the protection against ischemic stroke via microbiota-gut-brain axis.

Ischemic stroke (IS) has attracted worldwide attention due to the high mortality and disability rate. Raw rhubarb (RR) is a traditional medicinal plant and whole-food that has been used in China for its various pharmacological activities, such as antioxidant and anti-inflammatory properties. Recent pharmacological research has shown the role of RR against IS, but its mechanism of action remains unclear, particularly in the context of the brain-gut axis. To address this gap in knowledge, the present study was conducted in the middle cerebral artery occlusion/reperfusion (MCAO/R) model with the aim of investigating the effects of RR on regulating the intestinal microbiota barrier and metabolism and thereby reducing inflammatory response so as to improve the IS. The results showed that pre-treatment of RR attenuated cerebral infarct area and inflammation response in MCAO rats. Furthermore, RR also improved intestinal barrier function, including the integrity and permeability of the intestinal barrier. Additionally, RR intervention significantly attenuated gut microbiota dysbiosis caused by ischemic stroke, especially the increased Firmicutes. Notably, the pseudo-germ-free (PGF) rats further demonstrated that the anti-stroke effect of RR might rely on intestinal microbiota. In addition, the UPLC/Q-Orbitrap-MS-Based metabolomics revealed the disrupted metabolic profiles caused by MCAO/R, and a total of 11 differential metabolites were modulated by RR administration, especially bile acids. Further correlation analysis and network pharmacology analysis also demonstrated a strong association between specific bacteria, such as Firmicutes and bile acids. In conclusion, our work demonstrated that RR could effectively ameliorate ischemic stroke by modulating the microbiota and metabolic disorders.

Mitochondrial fumarate promotes ischemia/reperfusion-induced tubular injury.

AIM: Mitochondrial dysfunction, a characteristic pathological feature of renal Ischemic/reperfusion injury (I/RI), predisposes tubular epithelial cells to maintain an inflammatory microenvironment, however, the exact mechanisms through which mitochondrial dysfunction modulates the induction of tubular injury remains incompletely understood. METHODS: ESI-QTRAP-MS/MS approach was used to characterize the targeted metabolic profiling of kidney with I/RI. Tubule injury, mitochondrial dysfunction, and fumarate level were evaluated using qPCR, transmission electron microscopy, ELISA, and immunohistochemistry. RESULTS: We demonstrated that tubule injury occurred at the phase of reperfusion in murine model of I/RI. Meanwhile, enhanced glycolysis and mitochondrial dysfunction were found to be associated with tubule injury. Further, we found that tubular fumarate, which resulted from fumarate hydratase deficiency and released from dysfunctional mitochondria, promoted tubular injury. Mechanistically, fumarate induced tubular injury by causing disturbance of glutathione (GSH) hemostasis. Suppression of GSH with buthionine sulphoximine administration could deteriorate the fumarate inhibition-mediated tubule injury recovery. Reactive oxygen species/NF-κB signaling activation played a vital role in fumarate-mediated tubule injury. CONCLUSION: Our studies demonstrated that the mitochondrial-derived fumarate promotes tubular epithelial cell injury in renal I/RI. Blockade of fumarate-mediated ROS/NF-κB signaling activation may serve as a novel therapeutic approach to ameliorate hypoxic tubule injury.

Bedside ocular ultrasonography for diagnosing increased intracranial pressure in patients with leptomeningeal metastases from non-small-cell lung cancer.

OBJECTIVES: To explore the diagnostic accuracy of ultrasound measurement of optic nerve sheath diameter (ONSD) and optic disc height (ODH) in detecting intracranial hypertension in non-small-cell lung cancer (NSCLC) patients with leptomeningeal metastases (LM). METHODS: Seventy-two patients with NSCLC-LM and 65 patients with NSCLC were enrolled. The ONSD, ODH, eyeball transverse diameter (ETD), and eyeball vertical diameter (EVD) were measured by ultrasound. Subsequently, lumbar puncture was performed in NSCLC-LM patients to measure cerebrospinal fluid pressure (CSFP), and intrathecal chemotherapy was regularly implemented. Pearson's correlation analysis was used to analyze the relationship between CSFP and ultrasound findings. The diagnostic accuracy of ONSD, ODH, and combined ONSD and ODH was evaluated by receiver operating characteristic (ROC) curve analysis and the corresponding area under the ROC curve (AUC). RESULTS: The ONSD, ODH, ONSD/ETD, and ONSD/EVD values were higher in the NSCLC-LM group (all p < 0.05). The ONSD, ODH, ONSD/ETD, and ONSD/EVD values were all elevated in the abnormally elevated CSFP group (all p < 0.05). ONSD, ODH, ONSD/ETD, and ONSD/EVD were positively correlated with CSFP (r = 0.531, 0.383, 0.534, and 0.535, all p < 0.0001). The AUCs for ONSD, ODH, ONSD/ETD, and ONSD/EVD to detect CSFP >280 mmH2O were 0.787 (95% CI: 0.64-0.93, sensitivity 68.75%, specificity 91.07%), 0.885 (95% CI: 0.81-0.96, sensitivity 100%, specificity 69.64%), 0.765 (95% CI: 0.64-0.89, sensitivity 81.25%, specificity 64.29%), and 0.788 (95% CI: 0.64-0.93, sensitivity 56.25%, specificity 91.07%), respectively. When ONSD was combined with ODH, the AUC was 0.913 (95% CI: 0.83-0.99, sensitivity 87.85%, specificity 85.70%). Furthermore, intrathecal chemotherapy was associated with a downtrend in CSFP and ultrasound findings. CONCLUSION: There are important advantages of using bedside ultrasonography for detecting elevated CSFP in NSCLC-LM patients. Further research should be performed to evaluate the clinical significance of an enlarged ONSD and increased ODH in NSCLC-LM.

Engineering a Facile Aptamer "Molecule-Doctor" with Hairpin-Contained I-Motif Enables Accurate Imaging and Killing of Cancer Cells.

Herein, we subtly engineered a pH and membrane receptor dual-activatable aptamer therapeutic for bispecific tumor cell imaging and in situ drug release by utilizing a hairpin-contained i-motif as the acid-responsive element to be complementary with a tumor-targeted aptamer, named as an aptamer "molecule-doctor" (pH-Apt-MD). Specifically, the pH-Apt-MD consisted of two DNA strands, where the Apt-sgc8c was labeled with AF488 and Cy3 at its 5'- and 3'-end, respectively. The I-strand, a hairpin-contained i-motif, was complementary to the Apt-sgc8c strand partially, labeled with a BHQ2 in the middle, thus generating Cy3 with quenched fluorescence and only AF488-emitted fluorescence. The double-helix region of pH-Apt-MD was designed rich in GC bases, providing sites for doxorubicin (Dox) intercalation. Once target cells were encountered, the pH-Apt-MD disassembled due to the specific recognition of the aptamer and conformation change of the i-motif, with activated fluorescence resonance energy transfer (FRET) signals between AF488 and Cy3, accompanied by Dox release in situ. Benefiting from the design of the hairpin-contained i-motif, the pH-Apt-MD presented a narrow pH response range (pH 6.0-6.8) with a transition midpoint (pHT) of 6.50 ± 0.04. Furthermore, living cell studies revealed that the stimuli-responsive FRET signal activation of pH-Apt-MD was successfully achieved on the HCT116 cell surface with ultralow background and enhanced imaging contrast. Then, the cytotoxicity experiments proved that accurate drug release and cell killing were realized to target cells in an acidic microenvironment. As a facile double stimuli-responsive strategy, the pH-Apt-MD may hold great promise for application in precise diagnosis and therapy of cancer cells.

Integrated Analysis of the Cecal Microbiome and Plasma Metabolomics to Explore NaoMaiTong and Its Potential Role in Changing the Intestinal Flora and Their Metabolites in Ischemic Stroke.

Ischemic stroke (IS), as a leading cause of disability worldwide, affects intestinal bacterial communities and their metabolites, while recent discoveries have highlighted the importance of the intestinal microflora in the development of IS. Systematic investigations of complex intestinal bacterial communities and their metabolites during ischemic brain injury contribute to elucidate the promising therapeutic targets for IS. However, the associations between intestinal microbiota and related circulating metabolic processes in IS remained unclear. Hence, to identify the changed microflora and their metabolites in IS of NaoMaiTong (NMT), an effective clinical medication, we established the middle cerebral artery occlusion/reperfusion (MCAO/R) model using conventionalized and pseudo-germ-free (PGF) rats. Subsequently, we systematically screen the microflora and related metabolites changing in IS via an integrated approach of cecal 16S rRNA sequencing combined with plasma metabolomics. We found that NMT relied on intestinal flora to improve stroke outcome in conventionalized rats while the protection of NMT was reduced in PGF rats. Total 35 differential bacterial genera and 26 differential microbial metabolites were regulated by NMT. Furthermore, L-asparagine and indoleacetaldehyde were significantly negatively correlated with Lachnospiraceae_UCG.001 and significantly positively correlated with Lachnoclostridium. Indoleacetaldehyde also presented a negative correlation with Lactobacillus and Bifidobacterium. 2-Hydroxybutyric acid was strongly negatively correlated with Ruminococcus, Lachnospiraceae_UCG.001 and Lachnospiraceae_UCG.006. Creatinine was strongly negatively correlated with Akkermansia. In summary, the research provided insights into the intricate interaction between intestinal microbiota and metabolism of NMT in IS. We identified above differential bacteria and differential endogenous metabolites which could be as prebiotic and probiotic substances that can influence prognosis in stroke and have potential to be used as novel therapeutic targets or exogenous drug supplements.

Three Novel EGFR Mutations (750_758del, I759S, T751_I759delinsS) in One Patient with Metastatic Non-Small Cell Lung Cancer Responding to Osimertinib: A Case Report.

Generations of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) can significantly improve the outcome of EGFR-positive NSCLC patients. However, acquired TKIs-resistant mutations are inevitable. Except the common EGFR alterations, more and more rare mutations are revealed by next-generation sequencing (NGS), the clinical significance of which are still unclear. Here, we report an advanced lung adenocarcinoma patient who harbored two novel EGFR exon 19 deletions (750_758del and I759S) at the beginning and exhibited a short response to icotinib for 7.0 months. Then, secondary resistance EGFR T751_I759delinsS occurred. Chemotherapy combined with bevacizumab and erlotinib was administered in turn but failed. Standard-dose osimertinib (80 mg daily) obtained durable clinical remission for 16 months, and high-dose osimertinib (160 mg daily) further prolonged the survival of 9 months after leptomeningeal metastases (LM) occurring. This study presented the first case of intractable terminal NSCLC in a patient with EGFR 750_758del, I759S and T751_I759delinsS mutations, who responded positively to osimertinib and achieved a prolonged OS of 52 months, providing a potential therapeutic option for the patients harboring these particular EGFR mutations.

Treatment response to intrathecal chemotherapy with pemetrexed via an Ommaya reservoir in EGFR-mutated leptomeningeal metastases from non-small cell lung cancer: a case report.

Leptomeningeal metastasis (LM) is one of the most severe complications of non-small cell lung cancer (NSCLC), and it lacks standard treatment guidelines and is always accompanied by poor prognosis. We report a patient who was definitively diagnosed as LM from NSCLC with a targeted mutation of epidermal growth factor receptor (EGFR) via magnetic resonance imaging (MRI) and positive cerebrospinal fluid (CSF) cytology. Tyrosine kinase inhibitors (TKIs) were implemented but ineffective. Then the patient received the installation of an intraventricular Ommaya reservoir. Thirty mg of pemetrexed and other adjuvant treatments were implemented on days 1 and 8 every 3 weeks via the Ommaya reservoir. This treatment regimen resulted in the alleviation of the neurological symptoms, the clearing of CSF cytology and a reduced lesion of LM without notable side effects. At recent follow-ups, MRI examinations revealed the sustained stable LM lesion. We report the first successful example of administering intrathecal chemotherapy with pemetrexed via an Ommaya reservoir, providing a new therapeutic approach against LM from NSCLC.

[Auxiliary Diagnostic Value of Tumor Markers in the Cerebrospinal Fluid and Blood for Leptomeningeal Metastasis from Non-small Cell Lung Cancer].

BACKGROUND: Leptomeningeal metastasis (LM) is one of the most common causes of death in patients with advanced non-small cell lung cancer (NSCLC), which is defined as malignant cells spreading to meninges and cerebrospinal fluid (CSF). Therefore, early diagnosis and timely treatment are essential. CSF cytology is the gold standard for LM diagnosis, however, it has a low sensitivity for diagnosis and can't be used to evaluate the treatment effect. The aim of this study was to assess the clinical value of serum and CSF tumor markers (TM) in the diagnosis and treatment of NSCLC patients with LM. METHODS: Nineteen patients with NSCLC-LM and 27 patients with nonmalignant neurological diseases (NMNDs) were included. We tested the levels and positive rates of carbohydrate antigen (CEA), carbohydrate antigen-125 (CA125), cytokeratin 19 fragments (CYFRA21-1) and neurone specific enolase (NSE) in CSF and serum, compared the sensitivity and specificity in the diagnosis of LM between different groups, and analyzed the correlation of detection between serum and CSF. Finally, we measured serum and CSF TM dynamically in 2 patients with NSCLC developing LM in an attempt to correlate these with the treatment response of extracranial and intracranial, respectively. RESULTS: The levels and positive rates of TM in CSF and serum in LM group were higher than those in NMNDs (P<0.05). In LM group, the levels of CEA, CYFRA21-1 and CEA were significantly higher in CSF than that in the serum (P<0.05), whereas, there was no statistical significance in positive rates of TM between CSF and serum (P>0.05). In CSF, CYFRA21-1 has the highest sensitivity (88.2%) and CEA has the best specificity (92.3%) to distinguish patients between LM and NMNDs. For combined detection of CEA, CA125, CYFRA 21-1 and NSE in CSF, when at least CEA or NSE was positive in patients with LM, the sensitivity and negative predictive value were 100.0%, and the specificity was 74.1%. When both CYFRA21-1 and NSE were positive, the specificity and positive predictive value were 100.0%, and the sensitivity was 78.9%. Furthermore, subgroup analysis showed that the detection rates of TM in CSF cytology positive population was higher than that in typical abnormalities magnetic resonance imaging population, but there was no statistical difference (P>0.05). The detection of TM between serum and CSF in LM patients had no significant correlation. Moreover, biochemical properties of CSF from ventricle and lumbar puncture are similar, therefore evaluating the levels of TM in serum and CSF dynamically can be used to assess the extracranial and intracranial treatment effect, respectively. CONCLUSIONS: Our study demonstrates that Serum and CSF TM can work as an auxiliary clinical diagnostic tool, which has a potential value in early diagnosis of NSCLC patients with LM. Serial measurement of TM may play an important role in the clinical management of NSCLC patients with LM, which is worthy of further promotion and clinical application.

Self-Assembled DNA Nanostructures-Based Nanocarriers Enabled Functional Nucleic Acids Delivery.

Nucleic acids are recognized as the blueprints of life and the repositories of genetic information, which play essential roles in the "central dogma of molecular biology". As classical and specific nucleic acids, apart from carrying genetic information, functional nucleic acids (FNAs) perform many intriguing functions such as targeted recognition, therapy and enzymatic catalysis. FNAs with excellent biocompatibility provide great promise for future applications in bioanalysis, material science, and nanotechnology. Nevertheless, effective delivery of FNAs to the targeted location still suffers from one or more challenges, especially in the field of biomedicine. Encouragingly, DNA nanotechnology shows great potential for applications in bioimaging, biosensing, and molecules delivery. Importantly, it provides an unprecedented opportunity to design and synthesize a series of self-assembled DNA nanostructures with well-defined size, shape, surface chemistry, and function. Through Watson-Crick base-pairing rules, FNAs, including aptamers, DNAzymes, small interfere RNA (siRNA), antisense oligonucleotides (ASOs), and unmethylated cytosine-phosphate-guanine dinucleotide oligonucleotides (CpG ODNS), are successfully decorated with self-assembled DNA nanostructures for delivery. In this progress report, we focus on self-assembled DNA nanostructures-based nanocarriers to deliver FNAs for applications in cellular analysis and cancer theranostics. First, we briefly summarize the superior properties of the prospective nanocarriers and introduce the self-assembled DNA nanostructures. Then we mainly highlight the most recent achievements of self-assembled DNA nanostructures as comers for the delivery of FNAs. Finally, this review points to some of the current challenges in the applications of self-assembled DNA nanostructures as FNAs nanocarriers and provides an insight into the future perspectives of self-assembled DNA nanostructures-based nanocarriers for FNAs delivery.

Treatment Response To Osimertinib In EGFR-Mutated Leptomeningeal Metastases From Non-Small Cell Lung Cancer: A Case Series.

Therapy for leptomeningeal metastases (LM) from non-small cell lung cancer (NSCLC) is challenging, and conventional treatments have little impact on the disease course. We report three cases that were definitively diagnosed as LM from NSCLC with a mutation of epidermal growth factor receptor (EGFR) L858R. The systemic therapies of chemotherapy, local radiotherapy, and early generation tyrosine kinase inhibitors (TKIs) were implemented but ineffective. Three patients were treated with the third-generation TKI osimertinib at 80 mg daily, despite their different detection levels of T790M in the cerebrospinal fluid (CSF) and plasma, and achieved symptomatic remission, a decline of carcinoembryonic antigen (CEA) levels, and stable lesions. After the progression of LM, osimertinib at 160 mg daily further lengthened the quality of life and survival time of patients without any notable side effects during treatment. Recent related studies and our cases indicate that osimertinib has a positive effect on LM from EGFR-mutant NSCLC, regardless of T790M status.

[Use of Ommaya Reservoirs to Deliver Pemetrexed in Leptomeningeal Metastasis from Non-small Cell Lung Cancer: A Case Report and Review of the Literature].

Leptomeningeal metastasis (LM) is one of the most severe complications of non-small-cell lung cancer (NSCLC), and its incidence is increasing gradually with the progress of targeted therapies. There are currently no standard guidelines for the therapy of LM. Intrathecal chemotherapy is the mainstay of treatment for NSCLC patients with LM, but the optimal drug, administration route and mode, and dosage remain unclear. We report a case of LM from NSCLC, who received the intrathecal chemotherapy with pemetrexed by Ommaya reservoir after prior targeted therapies. This local treatment improved the quality of life, and obtained the clearing of CSF cytology and stable lesions of LM without any notable side effects. After confirmation of LM, the patient has survived 17 months until now. Here we report the first case to demonstrate the potential effectiveness of intrathecal pemetrexed by Ommaya reservoir for the treatment of LM of NSCLC, summarize the safety and effectiveness of intrathecal chemotherapy in combination with related literatures, and provide a new strategy for local treatment of LM in clinical.
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APOE genotype and age modifies the correlation between cognitive status and metabolites from hippocampus by a 2D (1)H-MRS in non-demented elders.

Purpose. To examine the associations among age, Apolipoprotein E (APOE) genotype, metabolic changes in the hippocampus detected by 2D (1)H magnetic resonance spectroscopy (MRS), and neuropsychological measures of cognition in non-demented elders. Materials and Methods. We studied a cohort of 16 cognitively normal controls (CN) and 11 amnestic mild cognitive impairment (aMCI) patients between 66 and 88 years old who were genotyped for APOE genetic polymorphism. Measurements of 2D(1)H-MRS metabolites were obtained in the hippocampus region. Adjusting by age among all subjects, the association between metabolic changes and cognitive function was measured by Spearman partial rank-order correlation. The effect of APOE status was measured by separating the subjects into APOE genotype subgroups, including the APOEε4 carriers and APOEε4 non-carriers. Results. In contrast to the CN group matched with age, gender, and education, aMCI patients showed increased myo-inositol (mI)/Creatine (Cr) ratio only in the right hippocampus. No differences were noted on N-acetylaspartate (NAA)/Cr and mI/NAA from bilateral hippocampus, and so was mI/Cr ratio in left hippocampus between aMCI and CN. The mI/Cr ratio from the right hippocampus in non-demented elders was negatively correlated with Montreal Cognitive Assessment (MoCA) scores. Whether ε4 genotype or age was added as a covariate, none of the correlation effects remained significant. Additionally, adjusting for age and APOE genotype together, there was no significant correlation between them. Conclusion. Since the higher mI/Cr from the right hippocampus of the patients with aMCI than those from CN, the mI/Cr could be a more specific predictor of general cognitive function in aMCI patients. There is an association between higher mI/Cr in right hippocampus and worse cognitive function for the non-demented older adults, and the correlation could be modified by APOE status and age. That provided a window on objectively understanding the mechanism between the brain metabolites and the influence factors in non-demented elders.

[Negative symptoms predict the improvement of social functioning of patients with schizophrenia].

OBJECTIVE: To identify predictive factors associated with the improvement of social functioning of schizophrenia patients in a community. METHODS: 101 schizophrenia patients undergoing community rehabilitation were assessed with the Positive and Negative Syndrome Scale (PANSS), Personal and Social Performance Scale (PSP), Self-Esteem Scale (SES), Family Function Questionnaire (APGAR), and the World Health Organization Disability Assessment Scale II (WHODAS-II) twice 6 months apart. Pearson correlation and hierarchical multiple linear regression analyses were performed to identify the influencing and predictive factors associated with the improvement of social functioning. RESULTS: The increase of PSP score was correlated with age (r = 0.220), reduced PANSS negative score (r = 0.468), reduced PANSS general score (r = 0.392), reduced PANSS total score (r = 0.472), and reduced WHODAS-II Score (r = 0.247). The predictive factors of the change of PSP score followed the following order: change of PANSS negative score [the change of coefficient of determination (deltaR2 ) = 0.197], age of onset (deltaR2 = 0.048), change of WHODAS-II score and psychiatric rehabilitation (deltaR2 = 0.031). CONCLUSION: Improvement of negative symptoms predicts the short-term improvement of social functioning of schizophrenia patients.

Angiotensin II promotes the progression of human gastric cancer.

The renin-angiotensin system (RAS) plays an important role in cardiovascular homeostasis, carcinogenesis­related angiogenesis and cell proliferation. The present study was undertaken to determine the expression of angiotensin (Ang) II, Ang II type 1 and 2 receptors (AT1R and AT2R), and the activity of the angiotensin­converting enzyme (ACE) in gastric cancer tissue. The study further examined the roles of Ang II in the growth of gastric cancer cells in nude mice and in the migration and proliferation of MKN45 human gastric cancer cells. Gastric cancer tissue samples were obtained from gastric cancer patients. The levels of Ang II, AT1R and AT2R, as well as ACE activity were increased in tissues from gastric cancer patients compared to healthy tissues. A gastric cancer model was established by intraperitoneally injecting MKN45 human gastric cancer cells in nude mice, intraperitoneally injecting Ang II and measuring the tumor size every two days. Ang II treatment caused an increase in the size and weight of the tumor mass in nude mice, whereas the AT1R antagonist losartan significantly inhibited the size and weight of the tumor. While Ang II enhanced the migratory and proliferative rate of MKN45 human gastric cancer cells, these were significantly reduced following treatment with losartan. These results indicate that RAS is activated in gastric cancer patients and Ang II promotes the progression of gastric cancer in nude mice, as well as the migration and proliferation of MKN45 human gastric cancer cells.

[Relationship between body mass index and volume ratio of brain gray matter in patients with first-episode schizophrenia].

OBJECTIVE: To analyze the relationship between psychotic symptoms and body mass index (BMI) and brain mass index in patients with first-episode schizophrenia. METHODS: We identified 97 patients with first-episode and drug-free schizophrenia and compared their BMI and scare MRI results with 97 healthy participants. RESULTS: There were no statistically significant differences in BMI, volume of white matter and volume of grey matter between the patients with schizophrenia and healthy participants. BMI was positively correlated with age and negatively correlated with gray matter volume and the ratio of gray matter volume in the healthy participants. No such correlations were found in the patients with schizophrenia. BMI were not correlated with the total score of PANSS, nor with the factor score of PANSS. CONCLUSION: BMI is positive correlated with age, but negatively correlated with gray matter volume and the ratio of gray matter volume in healthy adult. But such correlations disappear in patients with schizophrenia. BMI is not associated with the seriousness of psychotic symptoms.