Retraction Note: MicroRNA-199a regulates myocardial fibrosis in rats by targeting SFRP5.

The article "MicroRNA-199a regulates myocardial fibrosis in rats by targeting SFRP5", by M.-H. Chen, J.-C. Liu, Y. Liu, Y.-C. Hu, X.-F. Cai, D.-C. Yin, published in Eur Rev Med Pharmacol Sci 2019; 23 (9): 3976-3983-DOI: 10.26355/eurrev_201905_17827-PMID: 31115026 has been retracted by the authors. This paper has been questioned on PubPeer (https://pubpeer.com/publications/6417BECD38A43595A89D977A1CBDF8). In particular, concerns were raised about Figures 2C and 4C, potentially showing three panels with overlapping details of a single image. The corresponding author states they used the wrong figure during manuscript drafting, which led to picture reuse. For this reason, the authors decided to withdraw the manuscript. This article has been retracted. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/17827.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with gastric cancer.

The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with gastric cancer (GC), published in late 2022 and the updated ESMO Gastric Cancer Living Guideline published in July 2023, were adapted in August 2023, according to previously established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with GC. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with GC representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), coordinated by ESMO and the Japanese Society of Medical Oncology (JSMO). The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different Asian regions represented by the 10 oncological societies. The latter are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with GC across the different regions of Asia, drawing on the evidence provided by both Western and Asian trials, whilst respecting the differences in screening practices, molecular profiling and age and stage at presentation. Attention is drawn to the disparity in the drug approvals and reimbursement strategies, between the different regions of Asia.

Partial cellular reprogramming stably restores the stemness of senescent epidermal stem cells.

OBJECTIVE: Adult stem cell senescence and exhaustion are important drivers of organismal age. Restored stem cell self-renewal has revealed novel therapeutic targets for decreasing the incidence of age-associated diseases (AADs) and prolonging the human health span. Transient ectopic expression of the reprogramming factors Oct3/4, Sox2, Klf4 and c-Myc (collectively known as OSKM) in somatic cells can induce partial cellular reprogramming and effectively ameliorate their age-associated hallmarks. However, how this form of rejuvenation is applied to senescent stem cells remains unknown. MATERIALS AND METHODS: The Integrin-α6highCD71high epidermal stem cells (ESCs) with low self-renewal ability were sorted by flow cytometry and then treated by the interrupted reprogramming induced by transient expression of OSKM. The ability of secondary clones' generation and self-proliferation in vitro, as well as stem cell marker p63, were detected to determine their self-renewal ability. Besides, gene and protein of epidermal cell markers were detected to determine whether their cell identities were retained. Finally, DNA methylation age (eAge) and DNA dehydroxymethylase/methyltransferase were analyzed to explore the alternation of their global DNA methylation pattern during this rejuvenation. RESULTS: The partial reprogramming restored the youthful self-renewal and proliferation in senescent ESCs, including larger secondary clone generation, higher expression of stem cell marker p63 and proliferation marker Ki67, and faster proliferation speed, in each case without abolishing epithelial cellular identity. Moreover, the rejuvenation of adult stem cells could be maintained for 2 weeks after reprogramming factor withdrawal, which was more stable than that of differentiated somatic cells. Additionally, we found that partial reprogramming counteracted the acceleration of eAge in senescent epidermal stem cells and DNA methyltransferase 1 (DNMT1) may play a crucial role in this process. CONCLUSIONS: Partial reprogramming has high therapeutic potential for reversing adult stem cell age, providing an advanced way to treat AADs.

Associations of a family history of lupus with the risks of lupus and major psychiatric disorders in first-degree relatives.

BACKGROUND: Genetic factors link psychiatric disorders, particularly major depressive disorder (MDD), bipolar disorder, and obsessive-compulsive disorder (OCD), with systemic lupus erythematosus (SLE). Additionally, maternal SLE is a risk factor for long-term developmental problems, particularly learning disabilities, attention disorders, autism spectrum disorder (ASD) and speech disorders, in children. AIM: We aimed to determine whether first-degree relatives (FDRs) of patients with SLE have increased risks of SLE and major psychiatric disorders. DESIGN AND METHODS: Using the Taiwan National Health Insurance Research Database, we recruited 40 462 FDRs of patients with SLE as well as 161 848 matched controls. The risks of major psychiatric disorders, including schizophrenia, bipolar disorder, OCD, MDD, ASD and attention-deficit/hyperactivity disorder (ADHD), were assessed. RESULTS: The FDRs of patients with SLE had higher risks of SLE (reported as the adjusted relative risk and 95% confidence interval: 14.54; 12.19-17.34), MDD (1.23; 1.12-1.34), ADHD (1.60; 1.55-1.65), OCD (1.41; 1.14-1.74) and bipolar disorder (1.18; 1.01-1.38) compared with controls. Specifically, male FDRs of patients with SLE had higher risks of SLE and bipolar disorder, whereas female FDRs of patients with SLE had higher risks of MDD and OCD. Differences in the familial relationship (i.e. parents, children, siblings and twins) were consistently associated with higher risks of these disorders compared with controls. CONCLUSIONS: The FDRs of patients with SLE had higher risks of SLE, MDD, ADHD, OCD and bipolar disorder than the controls.

Inhibition of extracellular signal-regulated kinase downregulates endoplasmic reticulum stress-induced apoptosis and decreases brain injury in a cardiac arrest rat model.

Cerebral ischemia-reperfusion injury (CIRI) is the predominant cause of neurological disability after cardiac arrest/cardiopulmonary resuscitation (CA/CPR). The endoplasmic reticulum stress (ERs)-induced apoptosis plays an important role in neuronal survival/death in CIRI. Our previous studies reported that the extracellular signal-regulated kinase (ERK) inhibitor, PD98059, alleviates CIRI after CA/CPR. Whether ERs-induced apoptosis is involved in the neuroprotection of PD98059 remains unknown. This study aims to investigate the effects of ERK inhibition by PD98059 on ERs-induced apoptosis after CIRI in the CA/CPR rat model. The baseline characteristics of male adult Sprague-Dawley (SD) rats in all groups were evaluated before CA/CPR. The SD rats that survived from CA/CPR were randomly divided into 3 groups (n=12/group): normal saline group (1 ml/kg), dimethylsulfoxide (DMSO, the solvent of PD98059, 1 ml/kg) group, PD98059 group (0.3 mg/kg). Another 12 SD rats were randomly selected as the Sham group. Twenty-four hours after resuscitation, neural injury was assessed by survival rate, neurological deficit scores (NDS) and Nissl staining; apoptosis of brain cells was detected using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining; mRNA expression and protein levels of ERs-related protein BIP, PERK, ATF4 and CHOP were checked with RT-PCR and Western Blot. The results showed that there were no significant differences in baseline characteristics before CA/CPR among all groups. PD98059 significantly improved survival rate and NDS, increased the Nissl bodies in neurons, reduced apoptosis, downregulated the mRNA transcription and expression levels of BIP, PERK, ATF4 and CHOP at 24 h after CA/CPR. Our results demonstrate that inhibition of ERK by PD98059 alleviates ERs-induced apoptosis via BIP-PERK-ATF4-CHOP signaling pathway and mitigates CIRI in the CA/CPR rat model.

Blockade of fatty acid signalling inhibits lipopolysaccharide-induced macrophage recruitment and progression of apical periodontitis.

AIM: To examine the role of palmitic acid in lipopolysaccharide (LPS)-stimulated chemotaxis of macrophages and the potential contribution of saturated fatty acid in signalling during the pathogenesis of apical periodontitis. METHODOLOGY: J774, a mouse macrophage cell line, was used in the experiments. After treatment with LPS, proteolytic maturation of sterol regulatory element-binding protein-1c (SREBP-1c) and expression of fatty acid synthase (FASN) were examined by Western analysis. Levels of palmitic acid were measured by reverse phase-high performance liquid chromatography-mass spectrometry. Knockdown of SREBP-1c and FASN was accomplished by small interfering RNA technology. Secretion of CC-chemokine ligand 2 (CCL2) and cellular chemotaxis were assessed by enzyme-linked immunosorbent assay and transwell migration assay, respectively. Sulfo-N-succinimidyl oleate (SSO) treatment was used to inhibit fatty acid signalling in vitro and also in a rat model of apical periodontitis. All data were first subjected to Levene's test. In vitro data were then analysed using ANOVA followed by Tukey's multiple comparison test. Data from animal experiments were analysed by independent t-tests. The significant level was set at 0.05. RESULTS: LPS stimulated proteolytic maturation of SREBP-1c and FASN expression in macrophages and significantly enhanced palmitic acid synthesis (P < 0.05). Knockdown of SREBP-1c attenuated LPS-enhanced FASN expression. Knockdown of FASN significantly suppressed LPS-enhanced palmitic acid synthesis (P < 0.05). LPS and exogenous palmitic acid significantly enhanced CCL2 secretion and macrophage chemotaxis (all P < 0.05). Inhibition of FASN expression significantly alleviated LPS-augmented CCL2 secretion (P < 0.05). SSO significantly suppressed CCL2 secretion and macrophage chemotaxis augmented by LPS and palmitic acid (all P < 0.05). In a rat model of induced apical periodontitis, SSO treatment significantly attenuated progression of apical periodontitis and macrophage recruitment (all P < 0.05). CONCLUSIONS: LPS/SREBP-1c/FASN/palmitic acid signalling contributed to tissue destruction caused by bacterial infection. Modulation of lipid metabolism and signalling may be helpful for the management of apical periodontitis.

Follow-up management strategy for patients undergoing peritoneal dialysis during novel coronavirus pneumonia epidemic.

OBJECTIVE: The study aimed to explore the best follow-up management strategy for patients undergoing peritoneal dialysis (PD) during the novel coronavirus pneumonia (NCP) epidemic. PATIENTS AND METHODS: Patients undergoing PD who were followed up during the NCP epidemic by our hospital were enrolled in this study. Because of the need to control the epidemic, a follow-up system was established during the epidemic period, with WeChat, QQ, and the telephone as the main methods of communication. Outpatient and emergency follow-ups were carried out to ensure the safety of dialysis and the prevention and control of the epidemic. The follow-up strategy included response measures related to the epidemic situation, prevention of peritonitis related to PD, water and salt control, exercise guidance, and psychological care. According to the patient's condition, the appointment system was implemented, with one consulting room and one process for each patient. The emergency patients were isolated in accordance with the epidemic situation. RESULTS: Since January 2020, among the 580 patients undergoing PD who were followed up in our department and their families, none had NCP infection. During the epidemic period, the standard hemoglobin level and the inpatient rate decreased. Complications related to PD, such as peritonitis, cardiovascular complications caused by volume overload, and pulmonary infection, did not significantly increase, and the withdrawal rate and mortality rate decreased compared with those in the same period last year. CONCLUSIONS: The patient follow-up strategy during the epidemic period had a significant positive effect on preventing and controlling the epidemic. Furthermore, during the epidemic period, encouraging patients and caregivers to pay attention to protection at home, avoid going out, strengthen self-management, and other measures were beneficial to the control of kidney disease itself, which is worth promoting. The close relationship between doctors and patients during the epidemic had a positive effect on the occurrence of complications related to patients undergoing PD.

TPM4 aggravates the malignant progression of hepatocellular carcinoma through negatively regulating SUSD2.

OBJECTIVE: The aim of this study was to elucidate the role of TPM4 in the progression of hepatocellular carcinoma (HCC), and to explore the potential underlying mechanism by interacting with SUSD2. PATIENTS AND METHODS: TPM4 expression levels in 41 HCC tissues and paracancerous tissues were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The relationship between TPM4 level with the pathological indexes and overall survival of HCC patients was analyzed. TPM4 overexpression and knockdown models were constructed in Bel-7402 and Hep3B cells, respectively. Subsequently, Cell Counting Kit-8 (CCK-8) and transwell assay were conducted to assess the effects of TPM4 on the proliferative and migratory abilities of HCC cells. Dual-Luciferase reporter gene assay was performed to verify the binding relationship between TPM4 and SUSD2. In addition, the xenograft model was conducted in HCC-bearing mice administrated with Hep3B cells in vivo. Finally, the effect of TPM4 on the growth of HCC was explored. RESULTS: TPM4 was significantly upregulated in HCC tissues and cell lines. Higher rates of lymphatic and distant metastasis, as well as worse prognosis, were observed in HCC patients with higher expression level of TPM4. The overexpression of TPM4 significantly enhanced the viability and migration abilities of Bel-7402 cells. However, opposite results were observed after the knockdown of TPM4 in Hep3B cells. SUSD2 was verified to be the target of TPM4 and was negatively regulated by TPM4. SUSD2 was lowly expressed in HCC tissues and cell lines. Meanwhile, SUSD2 was considered to be responsible for TPM4-regulated progression of HCC. In mice administrated with Hep3B, the cells transfected with sh-TPM4, the tumor volume and weight of HCC were markedly reduced when compared with the controls. CONCLUSIONS: TPM4 level is correlated with high rates of lymphatic and distant metastasis, as well as poor prognosis of HCC patients. By negatively targeting SUSD2, TPM4 aggravates the progression of HCC by accelerating the proliferative and migratory abilities of HCC cells.

Increased risk of major depressive disorder among probands with psoriasis and unaffected siblings: a nationwide population-based study.

BACKGROUND: Previous studies have shown that patients with psoriasis have a higher risk of depression. However, the risk of major depressive disorder (MDD) among unaffected siblings of psoriasis probands remains unknown. This study aimed to investigate the risk of MDD among probands with psoriasis and unaffected siblings. METHODS: We selected subjects from the National Health Insurance Research Database (NHIRD) in Taiwan. Subjects were followed up from 01 January 1996 until a diagnosis of MDD, death or 31 December 2011. The Breslow-Cox model was used to calculate the adjusted relative risk (aRR). RESULTS: This study included 1094 probands with psoriasis, 1202 unaffected siblings and 4808 matched controls. Overall, 11.9% of the psoriasis probands (n = 130) and 2.5% of the unaffected siblings (n = 30) developed MDD, as compared with 1.1% of the controls (n = 52). Compared with controls, probands with psoriasis and unaffected siblings had aRRs of 10.60 [95% confidence interval (CI): 7.73-14.52] and 2.17 (95% CI: 1.44-3.28), respectively, for MDD. CONCLUSIONS: Probands with psoriasis and unaffected siblings have an increased risk of subsequently developing MDD. Further studies are needed to investigate the shared familial mechanisms underlying psoriasis and MDD.

MicroRNA-199a regulates myocardial fibrosis in rats by targeting SFRP5.

OBJECTIVE: Myocardial fibrosis seriously affects normal heart function. This study focused on the role of microRNA-199a in regulating rat myocardial fibrosis by targeting secreted frizzled-related protein 5 (SFRP5). MATERIALS AND METHODS: The in vitro myocardial fibrosis model was established by 10 µM isoproterenol (ISO) induction in cardiac fibroblasts (CFs) for 24 h. Expression levels of microRNA-199a, collagen I and α smooth muscle actin (α-SMA) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein levels of SFRP5 and transforming growth factor-ß1 (TGF-ß1) in CFs were detected by Western blot. The binding condition between microRNA-199a and SFRP5 was verified by luciferase reporter gene assay. After transfection of microRNA-199a inhibitor or SFRP5 overexpression plasmid, proliferative and migratory rates of CFs were determined by cell counting kit-8 (CCK-8) and transwell assay, respectively. RESULTS: ISO treatment remarkably upregulated microRNA-199a expression in CFs. Transfection of microRNA-199a inhibitor could inhibit proliferation, migration and cardiac fibroblast-to-myofibroblast transformation (CMT) of CFs. Luciferase reporter gene assay confirmed the binding of microRNA-199a to SFRP5 3'UTR. Moreover, SFRP5 overexpression reversed the effects of microRNA-199a inhibitor on proliferation, migration, and CMT of CFs. CONCLUSIONS: MicroRNA-199a deficiency can inhibit the proliferative and migratory potentials of CFs, as well as CMT by targeting SFRP5, thus exerting the protective effect on myocardial fibrosis.

Analysis of serum metabolite profiles in syphilis patients by untargeted metabolomics.

BACKGROUND: Global metabolomics analysis can provide substantial information on energy metabolism, physiology, possible diagnostic biomarkers and intervention strategies for pathogens. OBJECTIVE: To gain a better understanding of the mechanisms of syphilis and analysis of serum metabolite profiles in syphilis patients. METHODS: We conducted an untargeted metabolomics analysis of serum from 20 syphilis patients and 20 healthy controls. RESULTS: A total of 2890 molecular features were extracted from each sample, and the peak intensity of each feature was obtained. Distinct differential metabolites were identified by principal component analysis, partial least squares-discriminant analysis and hierarchical clustering analysis. Furthermore, five metabolites were identified as significantly different by Student's t-test, including trimethylamine N-oxide, l-arginine, lysoPC(18:0), betaine and acetylcarnitine. KEGG analysis showed that these differential metabolites were in various pathways, including Chagas disease, fatty acid biosynthesis, primary bile acid biosynthesis, Salmonella infection, ABC transporters, glycerophospholipid metabolism and choline metabolism. Among them, trimethylamine N-oxide was 3.922 times in patients with syphilis than healthy controls. CONCLUSION: Trimethylamine N-oxide may be used as an indicator to distinguish between syphilis patients and healthy controls. The changes in these metabolites suggest that Treponema pallidum affects the normal metabolic activity of host cells, providing some clues for elucidating the pathogenesis of T. pallidum.

Simvastatin alleviates bone resorption in apical periodontitis possibly by inhibition of mitophagy-related osteoblast apoptosis.

AIM: To assess the connection between mitophagy and hypoxia-induced apoptosis in osteoblasts and whether simvastatin alleviates bone resorption in apical periodontitis through modulation of mitophagy-related apoptosis. METHODOLOGY: Hypoxia-induced generation of reactive oxygen species in mitochondria and changes in mitochondrial membrane potential were evaluated, respectively, by MitoSOX and JC-1 fluorescence dye signalling. Accumulation of mitophagy markers PTEN-induced putative kinase 1 (PINK1) and Parkin in mitochondria was examined by Western blotting and immunofluorescence microscopy. Osteoblast apoptosis was assessed by Western analysis of cleaved-poly (adenosine diphosphate ribose) polymerase (PARP). In a rat model of induced apical periodontitis, the therapeutic effect of simvastatin and its action on osteoblast mitophagy and apoptosis were examined. anova, Fisher's and Student's t-test were used for data analysis. RESULTS: Hypoxia-induced mitochondrial dysfunction and stimulated mitophagy in osteoblasts. Hypoxia also provoked apoptosis in osteoblasts and inhibition of mitophagy decreased hypoxia-augmented apoptotic activity. Simvastatin alleviated hypoxia-induced mitochondrial dysfunction, mitophagy and apoptosis. The protective action of simvastatin against apoptosis was related to its antimitophagy activity. Experiments in the rat model of induced apical periodontitis supported the laboratory findings. Simvastatin treatment mitigated periapical bone loss and reduced the activities of apoptosis and mitophagy in regional osteoblasts. CONCLUSIONS: The results suggest that modulation of osteoblast mitophagy may help diminish bone loss associated with inflammation and has potential as an auxiliary therapy for apical periodontitis.

Works on heart, how about brain? Effect of hyperkalemia on focal cerebral ischemia/reperfusion injury in rats.

OBJECTIVE: To investigate the effects of hyperkalemia on the brain after I/R in h transient middle cerebral artery occlusion (tMCAO) model. MATERIALS AND METHODS: A total of 120 adult male SD rats were randomly assigned to four groups: (1) hyperkalemia 80 µg/g (HK80) group; (2) hyperkalemia 40 µg/g (HK40) group; (3) normal saline (NS) group; (4) sham (SH) group. The concentration of serum K+ was elevated in HK80 and HK40 groups. The transient middle cerebral artery occlusion (tMCAO) model was used to assess the effect of hyperkalemia on the brain after I/R. After 24 h reperfusion, the infarct volume and cell damage of rat's I/R brain tissue sections were analyzed. The concentration of K+, Ca2+ and calmodulin (CaM), the activity of Ca-ATPase, the expression of Western blot of Ca2+/calmodulin-dependent protein kinase II (CaMKII) and Na+/Ca2+ exchanger 1 (NCX1), were also measured. RESULTS: After 24 h reperfusion, compared with NS group, the two-hyperkalemia groups (HK80 and HK40) were with less infarct volume and cell damage, higher concentration of K+ but lower Ca2+ and CaM compared with NS group. The activity of Ca-ATPase was also elevated, the expression of CaMK II and NCX1 were down-regulated in the two hyperkalemia groups. CONCLUSIONS: Hyperkalemia could also ameliorate the brain I/R injury by alleviating calcium overload inhibiting the activity of NCX1, lowering the concentration of Ca2+.

Changes in the range of the medicinal herb Eriocaulon buergerianum Körnicke. (Eriocaulaceae) under climate change.

Eriocaulon buergerianum Körnicke. (Eriocaulaceae) is one of the most common and least expensive herbal medicines for eye disease. This species is facing potential threats from climate change. Insufficient biogeographic knowledge of this plant species can hinder its effective management for long-term population survival. We integrated ecological niche modelling (Biomod2) with 70 records of E. buergerianum and eight environmental variables to estimate changes in distribution over time. A core area Zonation algorithm was introduced to identify conservation priority areas. Our results indicate that the range of E. buergerianum will likely decrease in the future: the overall range change on average is -44.36 ± 21.56% (-3.70% to -77.73%); values of range loss and range gain are 45.79 ± 20.30% (9.29-78.19%) and 1.43 ± 1.53% (0.18-5.59%), respectively. According to conservation priority analysis, the mandatory reserve (top 5%), negotiable reserve (0.95-0.9) and partial reserve (0.9-0.8) areas are 19,799, 19,799 and 39,597 km2 , respectively. The areas identified as conservation priority are located in the southeast, especially in northern Taiwan and the Wuyi Mountains. Based on these results, we suggest a re-evaluation of the threatened status of this species, with a potential upgrade to the vulnerable (VU) category. To overcome the adverse conditions faced by populations of E. buergerianum in China, we propose a multi-faceted conservation strategy involving more complete resource assessment, a monitoring system, medical research focused on revealing medicinal components or substitutes, and a regional development plan that considers both wildlife and socio-economic issues.

Arsenic and five metal concentrations in the muscle tissue of bigeye tuna (Thunnus obesus) in the Atlantic and Indian Oceans.

White muscle concentrations of As, Cd, Cu, Fe, Se, and Zn were investigated in Atlantic- and Indian-bigeye tuna (BET) (Thunnus obesus) from 6 regions. As and Cd muscle concentrations were significantly higher in the Indian-BET than in the Atlantic-BET, whereas the Indian-BET caught in the waters off South Africa revealed the highest As, Se, and Zn muscle concentrations. Accordingly, multidimensional scaling separated them into two oceanic groups. Positive linear relationships between muscle Cd concentration and fork length (FL) were established in both oceans. For the other elements, only muscle-Fe and FL relationship was found in the Atlantic-BET. 10.3% of BET > 145 cm FL from both oceans possessed muscle Cd concentrations exceeding the food safety limit (0.1 µg g-1 wet weight) set by the European Commission. Increased Cd, Cu and Zn pollution was found in the Atlantic Ocean compared with previous data, with higher levels found in the Indian Ocean.

Co-aggregation of major psychiatric disorders in individuals with first-degree relatives with schizophrenia: a nationwide population-based study.

A previous genetic study has suggested that schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) share common disease-associated genes. However, whether individuals with first-degree relatives (FDRs) with schizophrenia have a higher risk of these major psychiatric disorders requires further investigation. This study used Taiwan's National Health Insurance Research Database and identified 151 650 patients with schizophrenia and 227 967 individuals with FDRs with schizophrenia. The relative risks (RRs) of schizophrenia and other major psychiatric disorders were assessed in individuals with FDRs with schizophrenia. The individuals with FDRs with schizophrenia exhibited higher RRs (95% confidence interval) of major psychiatric disorders, namely schizophrenia (4.76, 4.65-4.88), bipolar disorder (3.23, 3.12-3.35), major depressive disorder (2.05, 2.00-2.10), ASD (2.55, 2.35-2.77) and ADHD (1.31, 1.25-1.37) than were found in the total population. Several sensitivity analyses were conducted to confirm these results. A dose-dependent relationship was observed between the risks of major psychiatric disorders and the numbers of FDRs with schizophrenia. The increased risks of major psychiatric disorders were consistent in different family relationships, namely among parents, offspring, siblings and twins. Our study supports the familial dose-dependent co-aggregation of schizophrenia, bipolar disorder, major depressive disorder, ASD and ADHD, and our results may prompt governmental public health departments and psychiatrists to focus on the mental health of individuals with FDRs with schizophrenia.

The effect of dexmedetomidine on expressions of inflammatory factors in patients with radical resection of gastric cancer.

OBJECTIVE: To investigate the effect of dexmedetomidine on the expressions of inflammatory factors, T-lymphocyte subgroups and nuclear factor kappa-B (NF-κB) in peripheral blood monocytes in the perioperative period of radical resection of gastric cancer. PATIENTS AND METHODS: We selected 74 patients who were admitted to our hospital for radical resection of gastric cancer between January 2012 and October 2015. All patients were randomly divided into the dexmedetomidine group and the control group. Within 15 min before anesthesia induction, patients in the dexmedetomidine group received the intravenous injection of dexmedetomidine, while the same volume saline in the control group. During the operation, the initial dosage in the dexmedetomidine group was set as 1 µg/kg followed by 0.2 µg/kg•h intravenous injection to the end of operation. Three time points were selected: 15 min before anesthesia induction (T0), 1 h before the end of operation (T1) and 24 h after operation (T2). At these time points, we detected the levels of serum inflammatory factors using enzyme-linked immune sorbent assay (ELISA), immunoturbidimetry, and flow cytometer, respectively. RESULTS: The levels of IL-1ß, IL-6, TNF-α, NF-κB and CRP at T1 and T2 were significantly elevated compared with the levels at T0, and the amplitude of elevation in the control group was significantly larger than that in the dexmedetomidine group. The expression levels of T-lymphocyte subgroup in patients in both groups were decreased at T1 (compared with the levels at T0), and the decreasing extent of the ratio of CD4+ to CD8+ in the control group was significantly larger than that in the dexmedetomidine group. Meanwhile, we found that the percentages of CD3+ and CD4+ at T1 and T2 in the control group were significantly lower than those in the dexmedetomidine group. CONCLUSIONS: Dexmedetomidine can effectively reduce the release of inflammatory factors in patients that received the radical resection of gastric cancer, and the anti-inflammation effect may be exerted through downregulating the expression of NF-κB. Besides, dexmedetomidine can also alleviate the reduction in subgroups of CD3+ and CD4+, thereby ameliorating the impaired immune functions.