Based on serum metabolomics and gut microbiota technology, this study explores the effects and mechanisms of the water extract of Ziziphi Spinosae Semen(SZRW) and the petroleum ether extract of Ziziphi Spinosae Semen(SZRO) in improving depressive-like behaviors induced by sleep deprivation. A modified multi-platform water environment method was employed to establish a rat model of sleep deprivation. Depressive-like behaviors in rats were assessed through the sucrose preference test and forced swim test. The expression of barrier proteins, such as Occludin, in the colon was determined by immunofluorescence. UPLC-Q-Orbitrap MS was utilized to analyze the serum metabolic profiles of sleep-deprived rats, screen for differential metabolites, and analyze metabolic pathways. The diversity of the gut microbiota was detected using 16S rRNA gene sequencing. Spearman correlation coefficient analysis was conducted to assess the correlation between differential metabolites and gut microbiota. The results indicated that SZRO significantly increased the sucrose preference index and decreased the immobility time in the forced swim test in rats. A total of 34 differential metabolites were identified through serum metabolomics. SZRW and SZRO shared five metabolic pathways, including phenylalanine metabolism. SZRW uniquely featured taurine and hypotaurine metabolism, while SZRO uniquely featured linoleic acid metabolism and tyrosine metabolism. Correlation analysis revealed that SZRW could upregulate the abundance of Bilophila, promoting the production of indole-3-propionic acid and subsequently upregulating the expression levels of intestinal tight junction proteins such as ZO-1, Occludin, and Claudin-1. SZRO could indirectly influence metabolic pathways such as arginine metabolism and linoleic acid metabolism by upregulating the abundance of gut microbiota such as Coprococcus and Eubacterium species. Both SZRW and SZRO can regulate endogenous metabolism, including amino acids, energy, and lipids, alter the gut microbiota microecology, and improve depressive-like behaviors. SZRO demonstrated superior effects in regulating metabolic pathways and gut microbiota structure compared to SZRW. The findings of this study provide a scientific basis for elucidating the pharmacodynamic material basis of Ziziphi Spinosae Semen.
Animals ; Rats ; Gastrointestinal Microbiome/drug effects* ; Male ; Metabolomics ; Drugs, Chinese Herbal/administration & dosage* ; Depression/blood* ; Rats, Sprague-Dawley ; Sleep Deprivation/complications* ; Ziziphus/chemistry* ; Antidepressive Agents/administration & dosage* ; Behavior, Animal/drug effects* ; Humans

The relationship between hyperuricemia (HUA) and erectile dysfunction (ED) remains inadequately understood. Given that HUA is often associated with various metabolic disorders, this study aims to explore the multivariate linear impacts of metabolic parameters on erectile function in ED patients with HUA. A cross-sectional analysis was conducted involving 514 ED patients with HUA in the Department of Andrology, Jiangsu Province Hospital of Chinese Medicine (Nanjing, China), aged 18 to 60 years. General demographic information, medical history, and laboratory results were collected to assess metabolic disturbances. Sexual function was evaluated using the 5-item version of the International Index of Erectile Function (IIEF-5) questionnaire. Based on univariate analysis, variables associated with IIEF-5 scores were identified, and the correlations between them were evaluated. The effects of these variables on IIEF-5 scores were further explored by multiple linear regression models. Fasting plasma glucose ( β = -0.628, P < 0.001), uric acid ( β = -0.552, P < 0.001), triglycerides ( β = -0.088, P = 0.047), low-density lipoprotein cholesterol ( β = -0.164, P = 0.027), glycated hemoglobin (HbA1c; β = -0.562, P = 0.012), and smoking history ( β = -0.074, P = 0.037) exhibited significant negative impacts on erectile function. The coefficient of determination ( R ²) for the model was 0.239, and the adjusted R ² was 0.230, indicating overall statistical significance ( F -statistic = 26.52, P < 0.001). Metabolic parameters play a crucial role in the development of ED. Maintaining normal metabolic indices may aid in the prevention and improvement of erectile function in ED patients with HUA.
Humans ; Male ; Erectile Dysfunction/metabolism* ; Hyperuricemia/metabolism* ; Adult ; Middle Aged ; Cross-Sectional Studies ; Glycated Hemoglobin/metabolism* ; Blood Glucose/metabolism* ; Uric Acid/blood* ; Young Adult ; Triglycerides/blood* ; Adolescent ; Cholesterol, LDL/blood* ; Penile Erection/physiology* ; Surveys and Questionnaires

BACKGROUND:Allogeneic hematopoietic stem cell transplantation is an important treatment for malignant hematological diseases,and delayed postoperative platelet implantation is a common complication that seriously affects the quality of patient survival;however,there are no standard protocols to improve platelet implantation rates and prevent platelet implantation delays. OBJECTIVE:To compare the safety and efficacy of oral Herombopag Olamine versus subcutaneous recombinant human thrombopoietin for promoting platelet implantation in patients with malignant hematological diseases undergoing haploid hematopoietic stem cell transplantation. METHODS:Clinical data of 163 patients with malignant hematological diseases who underwent haploidentical hematopoietic stem cell transplantation from January 2016 to October 2022 were retrospectively analyzed.A total of 72 patients who started to subcutaneously inject recombinant human thrombopoietin at+2 days were categorized into the recombinant human thrombopoietin group;a total of 27 patients who started to orally take Herombopag Olamine at+2 days were categorized into the Herombopag Olamine group;and 64 patients who did not apply Herombopag Olamine or recombinant human thrombopoietin were categorized into the blank control group.The implantation status,incidence of acute graft-versus-host disease of degree II-IV within 100 days,1-year survival rate,1-year recurrence rate,and safety were analyzed in the three groups. RESULTS AND CONCLUSION:(1)The average follow-up time was 52(12-87)months.The implantation time of neutrophils in the blank control group,recombinant human thrombopoietin group,and Herombopag Olamine group was(12.95±3.88)days,(14.04±3.71)days,and(13.89±2.74)days,respectively,with no statistically significant difference(P=0.352);the implantation time of platelets was(15.16±6.27)days,(17.67±6.52)days,and(17.00±4.75)days,with no statistically significant difference(P=0.287).(2)The complete platelet implantation rate on day 60 was 64.06%,90.28%,and 92.59%,respectively,and the difference was statistically significant(P<0.001).The subgroup analysis showed that the difference between the blank control group and the recombinant human thrombopoietin group was statistically significant(P<0.001),and the difference between the blank control group and the Herombopag Olamine group was statistically significant(P=0.004).The difference was not statistically significant between the recombinant human thrombopoietin group and Herombopag Olamine group(P=0.535).(3)100-day II-IV degree acute graft-versus-host disease incidence in the blank control group,recombinant human thrombopoietin group,and Herombopag Olamine group were 25.00%,30.56%,and 25.93%,respectively,and the difference was not statistically significant(P=0.752).(4)The incidence of cytomegalovirus anemia,cytomegalovirus pneumonia,and hepatic function injury had no statistical difference among the three groups(P>0.05).(5)During the follow-up period,there was no thrombotic event in any of the three groups of patients.(6)The results showed that recombinant human thrombopoietin and Herombopag Olamine could improve the platelet implantation rate of malignant hematological disease patients after haploidentical hematopoietic stem cell transplantation,with comparable efficacy and good safety.

Objective To explore the behavioral patterns and hippocampal neurogenesis of CHD8+mice,and to provide behavioral and morphological basis for improving autism like behavior and neurogenesis.Methods Genotype of wild type(WT)and CHD8+/-mice was identified.Weight measurement was conducted on both male and female mice of the WT and CHD8+/-strains.Subsequently,a battery of behavioral tests was administered,which included three-chamber test,self-grooming test,nesting test,Y-maze spontaneous alternation test,food burial test,open-field test and light-dark transition test.Afterwards,the mice were administered 2％pentobarbital sodium(2 ml/kg)to induce anesthesia.Their brains were frozen with 4％paraformaldehyde,removed for photography and analysis to identify any alterations in brain size.Western blotting and immunofluorescent labeling were used to detect changes in the process of hippocampus neurogenesis.Results Western blotting analysis demonstrated a decrease in the amounts of chromodomain helicase DNA binding protein 8(CHD8)protein in both male and female mice with CHD8+genotype,as compared to WT mice.There were no notable disparities in body weight between male and female WT and CHD8+mice,as well as in brain size.The three-chamber social behavior test revealed that both male and female CHD8+/-mice had social deficiencies(P＜0.05).During the open field test,there was no significant difference in the total distance moved by male and female WT and CHD8+/-mice.However,the amount of time spent in the central region was considerably lower in CHD8+/-mice compared to the WT mice(P＜0.01).Furthermore,the light-dark transition test revealed that both male and female CHD8+/-mice spent considerably less time investigating the white box compared to the WT mice(P＜0.05).Nevertheless,there were no notable alterations found in self-grooming,nesting,spontaneous alternation of Y-maze,and food burial experiments.In addition,Western blotting result demonstrated a significant drop in doublecortin(DCX)expression(P＜0.001),and immunofluorescent staining revealed a notable reduction in the number of DCX+cells(P＜0.01)in the hippocampus of CHD8+/-mice.Conclusion CHD8+/-mice exhibit social disorders and anxiety-like behaviors,with a decrease in the number of newly generated neurons in the hippocampus and neurogenesis disorders.

This review aims to summarize the progress of multi-omics technologies in the study of antibi-otic resistance in Cronobacter,with the goal of gaining a deep understanding of its resistance mechanisms and providing a scientific basis for the development of new treatment methods and prevention strategies.By integrating genomics,transcriptomics,proteomics,and metabolomics,the study analyzes gene varia-tions,expression patterns,protein function changes,and metabolic pathway adjustments in Cronobacter.This includes the use of whole-genome sequencing to reveal gene variations related to antibiotic resist-ance,RNA-seq technology to monitor changes in gene expression patterns,proteomics to study protein expression and function,and metabolomics to analyze dynamic changes in metabolites.The research has found that factors such as biofilm formation and outer membrane proteins significantly affect the antibiotic resistance of Cronobacter.In addition,new potential influencing factors have been identified,including the expression changes of multidrug efflux pump genes,which may play a key role in enhancing antibiotic efflux and reducing intracellular antibiotic concentrations.Multi-omics technologies provide a comprehen-sive and in-depth perspective for the study of antibiotic resistance in Cronobacter,revealing multiple fac-tors and potential mechanisms that affect resistance.Although some new influencing factors have been i-dentified,their specific molecular mechanisms still require further investigation.The application pros-pects of multi-omics technologies are broad,and they are expected to provide important support for the development of new treatment methods and prevention strategies.

Objective:To compare the clinical effect of deproteinized calf blood extract (DCBE) eye drops and 0.3% sodium hyaluronate eye drops in the treatment of diabetic cataract patients with dry eye after phacoemulsification.Methods:A randomized controlled study was performed.A total of 112 patients (116 eyes) with type Ⅱ diabetes combined with cataract and dry eye who underwent phacoemulsification in the Eye Hospital of Shandong First Medical University from January 2022 to September 2022 were selected.Patients were divided into DCBE group (49 cases, 51 eyes) and sodium hyaluronate group (63 cases, 65 eyes) by the random number table method.Patients received DCBE eye drops and 0.3% sodium hyaluronate eye drops after surgery according to grouping.Preoperative and postoperative 1 week, 1 month subjective symptoms of dry eye, corneal edema grade, tear film breakup time (TBUT), corneal fluorescein staining (CFS) and Schirmer Ⅰ test (SⅠt) results were recorded and compared.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Eye Hospital of Shandong First Medical University (No.SDSYKYY202112-1).Written informed consent was obtained from each subject.Results:There were significant differences in dry eye symptom score, TBUT and SⅠt at different time points between before and after surgery ( Ftime=323.202, 102.771, 151.876; all P<0.001).Dry eye symptom score decreased and SⅠt increased in the two groups at 1 week and 1 month after surgery compared with before surgery, and the differences were statistically significant (all P<0.017).TBUT was longer at 1 week and 1 month after surgery compared with before surgery in the DCBE group, and TBUT at 1 month after surgery was longer than that before surgery in the sodium hyaluronate group, and the differences were statistically significant (all P<0.017).There were statistically significant differences in CFS scores between the two groups at different time points before and after surgery ( Fgroup=5.391, P=0.022; Ftime=142.402, P<0.001).The CFS scores of both groups at 1 week and 1 month after surgery were lower than those before surgery, and CFS scores in the DCBE group were lower than those in the sodium hyaluronate group, with statistically significant differences (all P<0.017).One week after surgery, the proportion of patients with corneal edema in the DCBE group was 5.9%(3/51), which was significantly lower than 20.0%(13/65) in the sodium hyaluronate group ( χ2=4.790, P=0.029). Conclusions:DCBE eye drops can promote corneal repair, stabilize tear film and improve dry eye discomfort in early postoperative period in diabetic cataract, and its overall effect is better than 0.3% sodium hyaluronate eye drops.

Objective:Exploring the role and mechanism of CHMP4C in regulating necroptosis during gastric can-cer development and progression.Method:The expression of CHMP4C in pan-cancer was analyzed by bioinformatics methods,and the expression of CHMP4C was detected in human normal gastric epithelial cells and GC cell lines by RT-qPCR and Western blot.Overexpression or knockdown of CHMP4C was performed in GC cell lines,and the effects of CHMP4C on the growth and proliferation of GC cells were detected using CCK-8 and clone formation assays.The CCK-8 experiment and Hoechst/PI double staining experiment were used to detect the changes in GC cell mortality and PI positive cell ratio after treatment with the necroptsis inducer TSZ or inhibitor necrostatin-1(Nec-1).Western blot assay was used to detect the protein and phosphorylation levels of RIPK1,RIPK3,and MLKL in GC cells.Result:CHMP4C was upregulated in GC tissues and cells.The CCK-8 and clone formation experiments showed that overex-pression of CHMP4C significantly improved the proliferation ability and colony formation efficiency of GC cells,while knockdown of CHMP4C significantly weakened GC cells.Moreover,the results of CCK-8 and Hoechst 33342/PI double staining experiments showed that upregulated CHMP4C could inhibit TSZ induced GC cell death;Nec-1 can reverse the decrease in GC cell viability caused by CHMP4C knockdown.Western blot experiment showed that the levels of p-RIPK1,p-RIPK3,and p-MLKL were significantly decreased in overexpressing cells,while they were increased in knockdown cells.After treatment with Nec-1,the expression levels of these three proteins decreased in knockdown cells.Conclusion:CHMP4C may promote GC progression by negatively regulating necroptosis through inhibiting the phosphorylation of the RIPK1/RIPK3/MLKL signaling pathway,suggesting that it is expected to be a potential target for GC therapy.

Objective To investigate iodine content in drinking water and clarify the distribution characteristics of iodine in water in Shaanxi Province.Methods A cross-sectional survey method was used to collect water samples from administrative villages in the province.Two tap water samples were taken from the centralized water supply villages,and 10％samples were taken from the decentralized water supply villages.Water iodine was detected by arsenic cerium catalytic spectrophotometry.Water iodine areas were divided according to national standards:＜40 μg/L was iodine deficiency area,40-100 μg/L was iodine adequate area,＞100 μg/L was high iodine area.According to the ecological regionification scheme of the Chinese Academy of Sciences,Shaanxi Province was divided into three types:the central and eastern Inner Mongolia Platea-Loess Plateau ecological region,the Fenwei Basin ecological region,and the Qinba Mountains ecological region.SPSS 25.0 was used for statistical analysis.Results The median of water iodine in Shaanxi Province was 6.66 μg/L.The survey of water iodine content was conducted in 22 848 administrative villages,1 309 townships,112 counties and 14 municipalities in the whole province.The median water iodine was less than 40 μg/L in 91.75％(20 963/22 848)of the administrative villages,between 40 and 100 μg/L in 7.40％(1 691/22 848)of the administrative villages,and more than 100 μg/L in 0.85％(194/22 848)of the administrative villages.The median of water iodine in the central and eastern Inner Mongolia Platea-Lose Plateau ecological zone,the Fenwei Basin ecological zone,and Qinba Mountains ecological zone was 12.35,8.88,and 2.00 μg/L,respectively,and the differences among different ecological zones were statistically significant(H=6 616.23,P＜0.001).The median of water iodine of centralized and decentralized water supply was 6.72 and 6.21 μg/L,respectively,and differences between different water supply methods were statistically significant(Z=5.638,P＜0.01).Conclusion The overall external environment of Shaanxi Province is iodine deficient,and most of the administrative villages are iodine deficient areas.There are a certain proportion of high iodine water source areas and suitable iodine areas.

Objective:To compare the clinical effect of deproteinized calf blood extract (DCBE) eye drops and 0.3% sodium hyaluronate eye drops in the treatment of diabetic cataract patients with dry eye after phacoemulsification.Methods:A randomized controlled study was performed.A total of 112 patients (116 eyes) with type Ⅱ diabetes combined with cataract and dry eye who underwent phacoemulsification in the Eye Hospital of Shandong First Medical University from January 2022 to September 2022 were selected.Patients were divided into DCBE group (49 cases, 51 eyes) and sodium hyaluronate group (63 cases, 65 eyes) by the random number table method.Patients received DCBE eye drops and 0.3% sodium hyaluronate eye drops after surgery according to grouping.Preoperative and postoperative 1 week, 1 month subjective symptoms of dry eye, corneal edema grade, tear film breakup time (TBUT), corneal fluorescein staining (CFS) and Schirmer Ⅰ test (SⅠt) results were recorded and compared.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Eye Hospital of Shandong First Medical University (No.SDSYKYY202112-1).Written informed consent was obtained from each subject.Results:There were significant differences in dry eye symptom score, TBUT and SⅠt at different time points between before and after surgery ( Ftime=323.202, 102.771, 151.876; all P<0.001).Dry eye symptom score decreased and SⅠt increased in the two groups at 1 week and 1 month after surgery compared with before surgery, and the differences were statistically significant (all P<0.017).TBUT was longer at 1 week and 1 month after surgery compared with before surgery in the DCBE group, and TBUT at 1 month after surgery was longer than that before surgery in the sodium hyaluronate group, and the differences were statistically significant (all P<0.017).There were statistically significant differences in CFS scores between the two groups at different time points before and after surgery ( Fgroup=5.391, P=0.022; Ftime=142.402, P<0.001).The CFS scores of both groups at 1 week and 1 month after surgery were lower than those before surgery, and CFS scores in the DCBE group were lower than those in the sodium hyaluronate group, with statistically significant differences (all P<0.017).One week after surgery, the proportion of patients with corneal edema in the DCBE group was 5.9%(3/51), which was significantly lower than 20.0%(13/65) in the sodium hyaluronate group ( χ2=4.790, P=0.029). Conclusions:DCBE eye drops can promote corneal repair, stabilize tear film and improve dry eye discomfort in early postoperative period in diabetic cataract, and its overall effect is better than 0.3% sodium hyaluronate eye drops.