This study aims to explore the mechanism of Jiaotai Pills in treating depression based on metabolomics and network pharmacology. The chemical constituents of Jiaotai Pills were identified by UHPLC-Orbitrap Exploris 480, and the targets of Jiaotai Pills and depression were retrieved from online databases. STRING and Cytoscape 3.7.2 were used to construct the protein-protein interaction network of core targets of Jiaotai Pills in treating depression and the "compound-target-pathway" network. DAVID was used for Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses of the core targets. The mouse model of depression was established with chronic unpredictable mild stress(CUMS) and treated with different doses of Jiaotai Pills. The behavioral changes and pathological changes in the hippocampus were observed. UHPLC-Orbitrap Exploris 120 was used for metabolic profiling of the serum, from which the differential metabolites and related metabolic pathways were screened. A "metabolite-reaction-enzyme-gene" network was constructed for the integrated analysis of metabolomics and network pharmacology. A total of 34 chemical components of Jiaotai Pills were identified, and 143 core targets of Jiaotai Pills in treating depression were predicted, which were mainly involved in the arginine and proline, sphingolipid, and neurotrophin metabolism signaling pathways. The results of animal experiments showed that Jiaotai Pills alleviated the depression behaviors and pathological changes in the hippocampus of the mouse model of CUMS-induced depression. In addition, Jiaotai Pills reversed the levels of 32 metabolites involved in various pathways such as arginine and proline metabolism, sphingolipid metabolism, and porphyrin metabolism in the serum of model mice. The integrated analysis showed that arginine and proline metabolism, cysteine and methionine metabolism, and porphyrin metabolism might be the key pathways in the treatment of depression with Jiaotai Pills. In conclusion, metabolomics combined with network pharmacology clarifies the antidepressant mechanism of Jiaotai Pills, which may provide a basis for the clinical application of Jiaotai Pills in treating depression.
Animals ; Drugs, Chinese Herbal/chemistry* ; Depression/genetics* ; Mice ; Network Pharmacology ; Metabolomics ; Male ; Disease Models, Animal ; Humans ; Protein Interaction Maps/drug effects* ; Antidepressive Agents

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

BACKGROUND: Early control of low-density lipoprotein cholesterol (LDL-C) is crucial for reducing the progress of cardiovascular disease. However, its additional role to the risk of primary osteoporosis in men with coronary heart disease was inconclusive. Our study aims to determine the association of LDL-C and its trajectories for osteoporosis risk in the middle-aged and aged men of China. METHODS: The retrospective cohort study of 1546 men aged 69.74 ± 11.30 years conducted in Beijing, China from 2015 to 2022. And the incidence of primary osteoporosis was annually recorded. LDL-C trajectories were further identified by latent class growth model using repeated measurements of LDL-C. The association of baseline LDL-C for osteoporosis was estimated using hazard ratio (HR) with 95% CI in Cox proportional hazard model, while mean level and trajectories of LDL-C for osteoporosis were evaluated using odds ratio (OR) with 95% CI in logistic regression model. RESULTS: During the median 6.2-year follow-up period, 70 men developed primary osteoporosis. The higher level of baseline LDL-C (HR = 1.539, 95% CI: 1.012-2.342) and mean LDL-C (OR = 2.190, 95% CI: 1.443-3.324) were associated with higher risk of osteoporosis in men with coronary heart disease after adjusted for covariates. Compared with those in the LDL-C trajectory of low-stable decrease, participants with medium-fluctuant trajectory, whose longitudinal LDL-C started with a medium LDL-C level and appeared an increase and then decrease, were negatively associated with osteoporosis risk (OR = 2.451, 95% CI: 1.152-5.216). And participants with initially high LDL-C level and then a rapid decrease demonstrated a tendency towards reduced risk (OR = 0.718, 95% CI: 0.212-2.437). CONCLUSIONS Elevated LDL-C level and its long-term fluctuation may increase the risk of primary osteoporosis in men. Early controlling a stable level of LDL-C is also essential for bone health.

Objective:To investigate the prognostic value of serum adenosylhomocysteinase (AHCY) in patients with hepatitis E virus acute liver failure (HEV-ALF).Methods:From 1 January 2017 to 31 December 2022, 100 patients each with HEV-ALF and acute hepatitis E (AHE) from the First Affiliated Hospital of Medical School of Zhejiang University and Affiliated Suzhou Hospital of Nanjing Medical University were included in this case-control study. The HEV-ALF group was 58.56±11.16 years old, including 71 men. The AHE group was 56.04±14.30 years old, including 61 men. All serum samples were obtained before the patient had an acute onset and were obtained without treatment. Firstly, the serum AHCY levels in patients with HEV-ALF and AHE were analyzed by ELISA. Secondly, the serum AHCY levels in HEV-ALF patients with different organ failure and disease condition were compared. According to the number of organ failure, 100 HEV-ALF patients were divided into organ failure number=2 group ( n=58), number=3 group ( n=24) and number>3 groups ( n=18). According to the disease condition, 100 patients were divided into improvement group ( n=49), disease fluctuation group ( n=37), and deterioration group ( n=14). Thirdly, the survival times between the high serum AHCY level group ( n=50) and the low serum AHCY level group ( n=50) were compared. Finally, the independent risk factors to predict mortality using the multivariate Logistic regression analysis, and evaluated the predictive and decision-making abilities of serum AHCY levels were explored using the receiver operating characteristic (ROC) curve and decision curve analysis (DCA). Results:Serum AHCY levels in HEV-ALF patients were significantly higher than those in AHE patients [326.92 (295.37-385.84) pg/ml vs. 222.88 (188.04-246.78) pg/ml, Z=-12.217, P<0.001]. Serum AHCY levels in group 2 were significantly lower than those in group 3 [303.44 (284.40-330.15) pg/ml vs. 335.36 (306.30-385.84) pg/ml, Z=-3.353, P=0.001]. Serum AHCY level in group 3 were significantly lowerthan those in group>3 [335.36 (306.30-385.84) pg/ml vs. 549.89 (423.35-660.22) pg/ml, P<0.001]. The serum AHCY levels in the fluctuation group were lower than those in the deterioration group [322.17 (283.92-423.74) pg/ml vs. 458.26 (374.66, 593.89) pg/ml, Z=-4.016, P=0.009]. The survival time of high serum AHCY level group was significantly lower than that of low serum AHCY level group [23.11 (20.25-25.96) days vs. 29.49 (28.79-30.20) days, Z=-2.596, P<0.001]. The multivariate Logistic regression analysis showed that the levels of serum AHCY and total bilirubin were independent risk factors to predict mortality in HEV-ALF patients [AHCY, OR (95% CI): 1.008 (1.002-1.015), P=0.008; total bilirubin, OR (95% CI): 1.011 (1.005-1.018), P=0.001]. Serum AHCY level predicting the area under the curve (AUC) of 30-day mortality in HEV-ALF patients was 0.912, with a sensitivity of 90.00% and a specificity of 93.75%. DCA results demonstrated that serum AHCY level had good decision-making power for predicting 30-day mortality in HEV-ALF patients. Conclusion:Serum AHCY has an important prognostic value for HEV-ALF patients. Higher serum AHCY levels indicate the worse prognosis of HEV-ALF patients.

Objective:To screen interleukin(IL)-1β secretion-related membrane transporters by macrophage experiment in vitro and conventional knockout mice.Methods:THP-1 cell line was differentiated to obtain human THP-1-derived macrophages,and the primary macrophages were obtained from human peripheral blood.FVB wild-type mice with the same sex and age were used as the controls of MRP1 knockout mice.The macrophages in abdominal cavity and bone marrow of mice were cultivated.The cells were treated with ABCC1/MRP1,ABCG2/BCRP,ABCB1/P-gp,OATP1B1,and MATE transporter inhibitors,then stimulated by lipopolysaccharide and adenosine triphosphate.The secretion level of IL-iβ was detected by ELISA,Western blot,and immunofluorescence.Results:After inhibiting ABCC1/MRP1 transporter,the secretion of IL-1β decreased significantly,while inhibition of the other 4 transporters had no effect.In animal experiment,the level of IL-1 β secreted by macrophages in bone marrow of MRP1 knockout mice was significantly lower than control group(P＜0.05).Conclusion:ABCC1/MRP1 transporter is a newly discovered IL-1β secretion pathway,which is expected to become a new target for solving clinical problems such as cytokine release syndrome.

Objective To investigate the value of 18F labeled prostate-specific membrane antigen(18F-PSMA)-1007 developing agent PET/CT(18F-PSMA-1007PET/CT)examination in the diagnostic evaluation and therapeutic decision of the newly diagnosed prostate cancer(PCa)and follow up after radical prostatecto-my(RP).Methods This study adopted the retrospective observational study method.A total of 68 patients receiving 18 F-PSMA-1007 PET/CT examination in this hospital from September 2022 to October 2023 were analyzed,including 36 cases of newly diagnosed PCa and 32 cases of biochemistry follow up failure after RP.A total of 30 items of clinical data were collected,including 8 items of basic clinical characteristics,7 items of pa-thology-related characteristics and 15 items of imaging characteristics.The patients clinical characteristics in the newly diagnosed PCa and biochemical failure after RP conducted the descriptive analysis.The Fisher exact probability method was used to analyze the differentiation of the SUVmax of primary lesions in different clini-cal subgroups[different tPSA levels at diagnosis,different mi-T stages,different Gleason scores at postopera-tive pathological puncture and different pathological types]in the newly diagnosed PCa group and the differ-entiation of recurrent lesion detection rates in different clinical subgroups(different tPSA in 18F-PSMA-1007 PET/CT examination,different pathological T stages,different lymph node invasion and different pathological Gleason scores in the biochemical failure after RP group.The Spearman correlation was adopted to test and analyze the correlation between the imaging features of positive lesions and tPSA.Results In the newly diag-nosed PCa group,there were 1 case of prostatic hyperplasia and 35 cases of PCa.SUVmax had no statistical differences among the primary lesions with different tPSA levels(P=0.81),different mi-T stages(P=0.70),different puncture Glleasonscores(P=0.20)and different pathological types(P=0.71).Moreover the tPSA value at diagnosis was positively correlated with the number of metastatic lesions(r=0.410,P=0.01).The clinical treatment decisions in 11 cases(31.43％)were changed according to the examination re-sults.In 9 cases of RP combined with lymph node dissection,the accuracy rate and concordance rate of 18F-PS-MA-1007 PET/CT and MRI in the lymph node detection rate all were 100％.I n the biochemical failure after RP group,the overall recurrent lesion detection rate was 71.88％(23/32),the operative area in situ recurrence(11 cases,34.38％)and bone metastasis(11 cases,34.38％)were most common.The differences of 18F-PS-MA-1007 PET/CT recurrent lesions detection rates had no statistical differences among the patients with dif-ferent tPSA levels(P=0.08),different pathological T stages(P=0.10),different postoperative pathological lymph node invasions(P=0.68)and different pathologic Gleason score in the 18F-PSMA-1007 PET/CT ex-amination.In the 18 F-PSMA-1007 PET/CT examination in the biochemical failure after RP,the tPSA value in the recurrent lesion was positively correlated with the number of recurrent lesions(r=0.48,P=0.01),SUVmax value in the recurrent lesion(r=0.46,P=0.01)and the SUVmean value(r=0.38,P=0.03).The clinical treatment decision in 18 cases(56.25％)was changed according to the examination results.Conclusion 18 F-PSMA-1007 PET/CT has good diagnostic value and efficiency for primary lesion and metastasis lesion of new-ly diagnosed PCa and recurrent foci of biochemical failure after RP.

Objective To investigate the clinical effect of apical microsurgery combined with guided bone regeneration(GBR)on refractory apical periodontitis and masticatory function.Methods A total of 82 patients with refractory apical periodontitis admitted to our hospital from June 2019 to September 2021 were selected as the study subjects,and they were divided into the control group and the com-bined group according to the random number table,with 41 cases in each group.The control group was treated with apical microsurgery,and the combined group was treated with apical microsurgery combined with GBR.The clinical efficacy,masticatory function and the levels of bone absorption markers[Wnt3a,osteoprotegerin(OPG),receptor activator of nuclear factor-κB ligand(RANKL)]of patients in the two groups were compared.Results The total effective rate of the combined group(100%)was higher than that of the control group(85.37%),the difference was statistically significant(P<0.05).The masticatory efficiency and bite force of patients in both groups increased gradually 3,6 and 12 months after operation(P<0.05),which were higher in the combined group compared with the control group(P<0.05).The tooth mobility of patients in both groups decreased gradually 3,6 and 12 months after operation,and the tooth mobility of patients 3 and 6 months after operation in the combined group were lower than those in the control group(P<0.05).The levels of Wnt3a and OPG of patients 1 week after operation in both groups increased,which were higher in the combined group compared with the control group(P<0.05).The RANKL level of gingival crevicular fluid of patients 1 week after operation in both groups decreased,and which was lower in the combined group compared with the control group(P<0.05).Conclusion The microapical surgery combined with GBR is effective for refractory apical periodontitis,which can effectively inhibit bone resorption,and improve masticatory function.

Objective To explore the relevant factors of new-onset conduction disturbance(NOCD)after transcatheter aortic valve replacement(TAVR),such as anatomical structure,device type,surgical strategies,etc.,discover relevant predictive factors,and establish a predictive model to assess the risk of conduction blockages.Methods From January 2016 to March 2022,clinical data of symptomatic patients with severe aortic valve stenosis or severe regurgitation who underwent TAVR at Xiangya Second Hospital of Central South University were collected through the hospital information system and imaging database.ECG,echocardiography,CTA,surgical materials,etc.,were extracted and analyzed by specialists.SPSS software was used for statistical analysis,and a multi-factor regression prediction model for NOCDwas built.Results A total of 184 patients were included,the occurrence rate of NOCD after TAVR was 31.0%,pure regurgitation patients'NOCD occurrence rate was 63.6%(7/11).The NOCD group had a larger aortic angles[(57.7±10.3)°vs.(52.0±9.0)°,P＜0.001],larger Oversizing[(129±28)%vs.(120±21)%,P=0.018],deeper implantation depth[(7.2±5.1)mm vs.(4.8±4.2)mm,P=0.001],and higher pure regurgitation patients'proportion[12.3%vs.3.1%,P=0.037]than the non-NOCD group.Multifactorial Logistic regression analysis indicated that an aorta angle＞54.5°(OR 3.78,95%CI 1.86-7.63,P＜0.001)or implantation depth＞5.7 mm(OR 3.39,95%CI 1.68-6.85,P＜0.001)are independent risk factors for new onset conduction disturbances after TAVR,and a predictive model was established with aortic angle,implantation depth,and Oversizing ratio as variables.The receiver operating characteristics curve showed area under ROC curve 0.709,95%CI 0.623-0.795,predicting NOCD after TAVR.Conclusions A retrospective analysis carried out at a single center discovered that the aortic angle in the NOCD group was larger than that in the non-NOCD group,the Oversizing ratio was higher,the implantation location was deeper,and there was a higher proportion of patients with pure regurgitation lesions.An aortic angle greater than 54.5°or an implantation depth more than 5.7 mm were identified as independent risk factors for NOCD after TAVR.

Objective:This study discusses the job preferences of Center for Disease Control and Prevention(CDC)staffs at the prefectural-level,and provides a basis for the development of an effective incentive mechanism.Method:This study used a combination of stratified sampling and purposive sampling to research online 455 staffs from six prefectural-level CDCs in Shandong Province,analyzed the data using a mixed logit model and latent class model,and calculated willingness to pay and relative importance.Result:In the mixed logit model,income,benefit level,establishment,workload,recognition and respect from the public,personal career development opportunities,and training opportunities all had significant influences(P<0.05)on the job selection preferences of the CDC staffs,with hygiene factors such as establishment(β =2.636)and income(β =0.083)having a greater degree of influence than motivation factors.The latent class model shows that relatively young CDC staffs with lower monthly incomes value income more;older CDC staffs with higher monthly incomes value establishment more.Conclusion:Prefectural-level CDC staffs prefer jobs with establishment,higher incomes,very good benefit levels,recognition and respected from the public,lower workloads,many opportunities for personal career advancement and abundant training opportunities.It is recommended that the total number of establishments be rationally controlled and dynamically adjusted to balance the differences between working conditions within and outside the establishment and that the financial input to CDC be increased and the pay performance system be improved;that attention be paid to both hygiene factors and motivation factors,and that a variety of measures work together to incentivize CDC staffs development;and that differentiated incentives be adopted for different categories of CDC staffs.

Tuberous sclerosis complex(TSC)is a rare genetic disease that can lead to benign dysplasia in multiple organs such as the skin, brain, eyes, oral cavity, heart, lungs, kidneys, liver, and bones. Its main symptoms include epilepsy, intellectual disabilities, skin depigmentation, and facial angiofibromas, whilst incidence is approximately 1 in 10 000 to 1 in 6000 newborns. This case presents a middle-aged woman who initially manifested with epilepsy and nodular depigmentation. Later, she developed a lower abdominal mass, elevated creatinine, and severe anemia. Based on clinical features and whole exome sequencing, the primary diagnosis was confirmed as TSC. Laboratory and imaging examinations revealed that the lower abdominal mass originated from the uterus. CT-guided biopsy pathology and surgical pathology suggested a combination of leiomyoma and abscess. With the involvement of multiple organs and various complications beyond the main diagnosis, the diagnostic and therapeutic process for this patient highlights the importance of rigorous clinical thinking and multidisciplinary collaboration in the diagnosis and treatment of rare and challenging diseases.