BackgroundSchizophrenia is a complex， chronic and severe mental disorder， and the pathogenesis of which has not been fully elucidated. The abnormalities in lipid metabolism and circulating metabolomes have already been implicated in the pathophysiology of schizophrenia. However， available studies have mainly focused on a few liposomes and circulating metabolites， failing to systematically reveal the mediating role of circulating metabolomes in the causal relationship between liposomes and schizophrenia. ObjectiveTo uncover mediating role of circulating metabolomes in the causal relationship between liposomes and schizophrenia， thereby providing biomarkers and potential therapeutic targets for the prevention and treatment of schizophrenia. MethodsData from Genome-Wide Association Studies （GWAS） were analyzed， taking data on 179 liposomes as exposure variables， data on 123 circulating metabolites as intermediate variables， and data on schizophrenia as outcome variable. A two-step， two-sample Mendelian randomization analysis was conducted using the inverse-variance weighted （IVW）， MR- Egger， Weighted median， and Weighted mode methods to study the causal relationship of liposomes with schizophrenia and the mediating role of circulating metabolomes in the relationship. ResultsIVW model identified 8 lipids associated with schizophrenia without reverse causality. There were 5 circulating metabolomes strongly associated with schizophrenia. Acetate played a significant mediating role in the causal relationship between phosphatidylinositol （18：0_18：2） and schizophrenia （P=0.023， 95% CI： 0.036~0.532）， accounting for 28.4% of the causal relationship. ConclusionThis study demonstrates a causal relationship between liposomes and schizophrenia， with phosphatidylinositol being a risk factor in the progression of schizophrenia， and acetate playing a mediating role in this process. ［Fund by National Natural Science Foundation of China General Program （number， 82271546）； Shanxi Merit Funding for Overseas Students Sci-Tech Activities Project （number， 20240041）； Shanxi Province Science and Technology Innovation Leading Talent Team Project （number， 202304051001049）； Shanxi Scientific Research Foundation for the Returned Overseas Chinese Scholars （number， 2022-190）； "Six Measures for Health Care Prosperity" Specialized Research Program （number， Y2024008）］

Objective To investigate the clinical efficacy and safety of endoscopic ultrasonography-guided(EUS-guided)enterocolon anastomosis in treating patients with malignant bowel obstruction(MBO).Methods The clinical data of 12 patients with MBO,who underwent EUS-guided enterocolon anastomosis at the Nanjing Drum Tower Hospital of China from April 2023 to December 2023,were collected.The perioperative clinical efficacy and safety were retrospectively analyzed.Results Successful EUS-guided enterocolon anastomosis was accomplished in all the 12 patients,with a technical success rate of 100％(12/12).The clinical success rate was 83.3％(11/12),one patient developed obstruction of the stent.The clinical symptoms were relieved in 2-68 hours after treatment,and the time to resume defecation and exhaust was(18.02±15.75)hours.Within one week after the operation,4 patients took liquid diet and 8 patients took semi-fluid diet.Each dimension score of the Quality of Life Core-30 scale of The European Organization for Research and Treatment of Cancer(EORTC QLQ-C30)was remarkably improved,the patient's overall health score was increased from preoperative median 5 points to postoperative 8 points(P＜0.001).During the operation,stent displacement occurred in 2 patients,and the operation was successfully completed after promptly taking remedial measures.After operation,11 patients developed fever(37.5-39.4 ℃),and all the patients were discharged smoothly after symptomatic treatment.No complication such as bleeding,perforation,or stent displacement occurred.Conclusion EUS-guided enterocolon anastomosis is clinically safe and effective,it can effectively relieve the clinical symptoms and improve the quality of life of patients with MBO.

Objective To investigate the relationship between thyroid stimulating hormone(TSH) and uric acid (UA), blood pressure, blood glucose, blood lipid and body mass index (BMI) in patients with type 2 diabetes. Methods A total of 254 patients with type 2 diabetes and normal thyroid function who were admitted to the Shengjing Hospital Affiliated to China Medical University from 2017 to 2019 were selected. Height, weight, systolic blood pressure (SBP) and diastolic blood pressure (DBP) and test fasting blood glucose (FBG), glycated hemoglobin (HbA1c), total cholesterol (TC), triacylglycerol (TG), low density lipoprotein cholestorol (LDL-C), free triiodothyronine (FT3), free theroxine (FT4), TSH and UA was measured. The correlations between TSH and blood pressure, blood lipid, FBG, BMI and UA was analyzed. Results According to gender, there were two groups. The levels of FT3, UA and BMI of males were significantly higher than that of females (P<0.05). Age, course of disease, TSH and TC of females were significantly higher than that of males (P<0.05). According to the TSH values of males and females, 254 patients were divided into TSH < 2.5 mU/L group and TSH ≥ 2.5 mU/L group respectively. The levels of BMI, FBG and UA in TSH≥2.5 mU/L group were significantly higher than those in TSH<2.5 mU/L group within females:(26.38 ± 4.06)kg/m2 vs.(23.91 ± 2.79)kg/m2,(10.29 ± 4.52)mmol/L vs. (8.38 ± 2.72)mmol/L,(406.53 ± 79.48)μmol/L vs.(270.17 ± 17.15)μmol/L. The levels of BMI, DBP and UA in TSH≥2.5 mU/L group were significantly higher than those in TSH<2.5 mU/L group within males:(27.87 ± 3.85)kg/m2 vs.(25.09 ± 3.10)kg/m2,(85.98 ± 9.75)mmHg(1 mmHg＝0.133 kPa) vs. (80.79 ± 8.44)mmHg,(430.35 ± 101.01)μmol/L vs.(318.10 ± 65.25)μmol/L, and the differences were statistically significant (P<0.05). Pearson correlation analysis was used to analyze the correlation between TSH and various indexes of all selected subjects. Only BMI, UA, FT4 and TG were statistically significant, and the correlation coefficients were 0.297, 0.550, - 0.208 and 0.127, P < 0.05, respectively. BMI, FBG and UA levels of females were positively correlated with TSH (P < 0.05), and the correlation coefficients were 0.332, 0.219 and 0.632, respectively. BMI, DBP, HbA1c and UA of males were positively correlated with TSH (P<0.05), and the correlation coefficients were 0.316, 0.204, 0.176 and 0.541, respectively. FT4 was negatively correlated with TSH, with a correlation coefficient of 0.248, which was statistically significant (P < 0.05), and UA had a stronger correlation with TSH. Conclusions Even in type 2 diabetics with normal thyroid function, small changes in TSH can affect weight, UA, FBG in women and DBP in men.

Objective To determine the expression of cathepsin L2 (CTSL2)and evaluate its activity in skin lesions of seborrheic keratosis (SK),to observe the ultrastructural changes of melanosomes in the skin lesions of SK,and to estimate the effect of CTSL2 on the degradation of melanosomes.Methods Twenty patients with SK were enrolled from the Department of Dermatology,Renmin Hospital of Wuhan University.The lesional tissue and the perilesional normal skin were biopsied from each patient.Among 15 of the 20 patients,hematoxylin and eosin (HE)staining and Fontana-Masson silver staining were performed to observe the distribution of melanin granules,transmission electron microscopy (TEM)was conducted to observe the ultrastructural changes of melanosomes,and immunohistochemical staining was performed to estimate the cellular proliferative activity.RT-PCR and fluorogenic substrate cleavage assay were performed in the other 5 patients to determine the mRNA expression of CTSL2 and evaluate its activity,respectively.Sucrose density gradient ultracentrifugation was performed to isolate and purify melanosomes from the retinal pigment epithelium (RPE) harvested from a discarded eyeball of a 35-year old male patient with informed consent.The purified melanosomes were incubated with epidermal lysates of SK lesions,and TEM was used to observe the changes in the membrane structure of melanosomes.Statistical analysis was carried out by paired t test,and a P value ＜ 0.05 was considered statistically significant.Results A large number of melanin granules were deposited in SK lesions,while the linear deposition of melanin granules was only seen in the basal layer of the normal skin.TEM showed that the percentage of damaged melanosomes was much higher in the normal skin (49.00％ ± 4.00％) than in the SK lesions (24.33％ ± 3.06％)(t =8.49,P ＜ 0.05).RT-PCR revealed that the mRNA expression and activity of CTSL2 were both significantly lower in the SK lesions than in the normal skin (mRNA:0.35 ± 0.09 vs.0.43 ± 0.08,t =3.17,P ＜ 0.05;activity:17.46 ± 0.45 vs.28.78 ± 0.58,t =34.29,P ＜ 0.05).Moreover,TEM also showed that the percentage of damaged melanosome was lower in the SK lesion lysate-treated group (32.33％ ± 4.93％) than in the normal skin lysate-treated group (43.00％ ± 2.65％,t =3.30,P ＜ 0.05).Conclusion Decreased expression of CTSL2 in the SK lesions can affect the degradation of melanosomes by keratinocytes.However,whether CTSL2 directly takes part in the pathogenesis of SK or not is still needed to be further confirmed.

Kinetin (Kn) is a cytokinin growth factor that exerts several anti-aging and antioxidant effects on cells and organs. To investigate the mechanism underlying apoptotic events in aging cells induced by D-galactose (D-gal), we examined the effect of Kn delivered via nuchal subcutaneous injection on D-gal-induced aging and apoptosis in rats. Our results showed that interleukin (IL)-2 levels and mitochondrial membrane potential (DeltaPsim) were decreased by Kn in aging rats while IL-6 production and apoptosis increased. In addition, the expression of anti-apoptotic Bcl-2 was low while that of Bax was high in the aging group. After treated with Kn, compared with aging group, there showed obvious difference in Kn group with elevated IL-2, proliferation index, Bcl-2, DeltaPsim and decreased IL-6 and Bax in splenic lymphocyte. Based on these results, we concluded that Kn can effectively protect the rat spleen from aging, apoptosis, and atrophy.
Aging/drug effects/physiology ; Animals ; Apoptosis/drug effects/*physiology ; Female ; Galactose/*pharmacology ; Interleukin-6/physiology ; Interleukins/physiology ; Kinetin/pharmacology/*physiology ; Male ; Membrane Potential, Mitochondrial/drug effects/physiology ; Rats ; Spleen/*cytology/drug effects/physiology