This study aimed to explore the pharmacological mechanism of Yourenji Capsules(YRJ) in improving osteoporosis by combining network pharmacology and proteomics technologies. The SD rats were randomly divided into a blank control group and a 700 mg·kg~(-1) YRJ group. The rats were subjected to gavage administration with the corresponding drugs, and the blank serum, drug-containing serum, and YRJ samples were compared using ultra performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS) to analyze the main components absorbed into blood. Network pharmacology analysis was conducted based on the YRJ components absorbed into blood to obtain related targets of the components and target genes involved in osteoporosis, and Venn diagrams were used to identify the intersection of drug action targets and disease targets. The STRING database was used for protein-protein interaction(PPI) network analysis of potential target proteins to construct a PPI network. Gene Ontology(GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment were performed using Enrichr to investigate the potential mechanism of action of YRJ. Ovariectomy(OVX) was performed to establish a rat model of osteoporosis, and the rats were divided into a sham group, a model group, and a 700 mg·kg~(-1) YRJ group. The rats were given the corresponding drugs by gavage. The femurs of the rats were subjected to label-free proteomics analysis to detect differentially expressed proteins, and GO functional enrichment and KEGG pathway enrichment analyses were performed on the differentially expressed proteins. With the help of network pharmacology and proteomics results, the mechanism by which YRJ improves osteoporosis was predicted. The analysis of the YRJ components absorbed into blood revealed 23 bioactive components of YRJ, and network pharmacology results indicated that key targets involved include tumor necrosis factor(TNF), tumor protein p53(TP53), protein kinase(AKT1), and matrix metalloproteinase 9(MMP9). These targets are mainly involved in osteoclast differentiation, estrogen signaling pathways, and nuclear factor-kappa B(NF-κB) signaling pathways. Additionally, the proteomics analysis highlighted important pathways such as peroxisome proliferator-activated receptor(PPAR) signaling pathways, mitogen-activated protein kinase(MAPK) signaling pathways, and β-alanine metabolism. The combined approaches of network pharmacology and proteomics have revealed that the mechanism by which YRJ improves osteoporosis may be closely related to the regulation of inflammation, osteoblast, and osteoclast metabolic pathways. The main pathways involved include the NF-κB signaling pathways, MAPK signaling pathways, and PPAR signaling pathways, among others.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Osteoporosis/metabolism* ; Proteomics ; Rats ; Rats, Sprague-Dawley ; Network Pharmacology ; Female ; Protein Interaction Maps/drug effects* ; Capsules ; Humans ; Signal Transduction/drug effects*

OBJECTIVE: Observational studies have found associations between inflammatory bowel disease (IBD) and the risk of dementia, including Alzheimer's dementia (AD) and vascular dementia (VD); however, these findings are inconsistent. It remains unclear whether these associations are causal. METHODS: We conducted a meta-analysis by systematically searching for observational studies on the association between IBD and dementia. Mendelian randomization (MR) analysis based on summary genome-wide association studies (GWASs) was performed. Genetic correlation and Bayesian co-localization analyses were used to provide robust genetic evidence. RESULTS: Ten observational studies involving 80,565,688 participants were included in this meta-analysis. IBD was significantly associated with dementia (risk ratio [ RR] =1.36, 95% CI = 1.04-1.78; I ² = 84.8%) and VD ( RR = 2.60, 95% CI = 1.18-5.70; only one study), but not with AD ( RR = 2.00, 95% CI = 0.96-4.13; I ² = 99.8%). MR analyses did not supported significant causal associations of IBD with dementia (dementia: odds ratio [ OR] = 1.01, 95% CI = 0.98-1.03; AD: OR = 0.98, 95% CI = 0.95-1.01; VD: OR = 1.02, 95% CI = 0.97-1.07). In addition, genetic correlation and co-localization analyses did not reveal any genetic associations between IBD and dementia. CONCLUSION Our study did not provide genetic evidence for a causal association between IBD and dementia risk. The increased risk of dementia observed in observational studies may be attributed to unobserved confounding factors or detection bias.
Humans ; Mendelian Randomization Analysis ; Inflammatory Bowel Diseases/complications* ; Dementia/etiology* ; Observational Studies as Topic ; Genome-Wide Association Study

OBJECTIVE: To explore the clinical significance of circulating tumor DNA (ctDNA) in response evaluation and relapse monitoring for patients with primary mediastinal large B-cell lymphoma (PMBCL). METHODS: The clinical characteristics, efficacy and survival of 38 PMBCL patients in our hospital from January 2010 to April 2020 were retrospectively analyzed. The ctDNA monitoring was conducted by targeted next-generation sequencing (NGS). RESULTS: Among the 38 patients, 26 cases were female, and 32 cases were diagnosed with Ann Arbor stage I-II. The 5-year overall survival (OS) rate and progression-free survival (PFS) rate were 74.7% and 61.7%, respectively. Males and those with high aaIPI scores (3 points) had a relatively poor prognosis. The NGS results of 23 patients showed that STAT6 (65.2%), SOCS1 (56.5%), and TNFAIP3 (56.5%) were the most common mutated genes. Patients with stable disease (SD)/progressive disease (PD) exhibited enrichment in cell cycle, FoxO, and TNF signaling pathways. A total of 29 patients underwent end-of-treatment PET/CT (EOT PET/CT), and 16 of them received ctDNA monitoring with 12 negative. Among 6 patients with EOT PET/CT positive (Deauville 4), 4 underwent ctDNA monitoring, and 3 of them were negative, being still in continuous remission without any subsequent anti-tumor therapy. CONCLUSION CtDNA may be combined with PET/CT to assess efficacy, monitor relapse, and guide treatment of PMBCL.
Humans ; Circulating Tumor DNA/blood* ; Female ; Mediastinal Neoplasms ; Male ; Retrospective Studies ; High-Throughput Nucleotide Sequencing ; Prognosis ; Lymphoma, Large B-Cell, Diffuse/genetics* ; Middle Aged ; Adult ; Aged ; Neoplasm Recurrence, Local ; Mutation

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Objective To investigate the therapeutic effects of upper limb rehabilitation robot training combined with intermittent theta burst stimulation(iTBS)on upper limb motor and neurological function in stroke patients with hemiplegia.Methods This study retrospectively consecutive enrolled 46 stroke hemiparetic patients from the Department of Rehabilitation Medicine,Nanjing Pukou People's Hospital.The patients were randomly assigned to a control group and an experimental group(23patients in each)using a random number table.Baseline data,including sex,age,disease duration,side of hemiplegia,and stroke type,were collected from patients enrolled.All patients received conventional treatment.The control group received upper limb rehabilitation robot training combined with iTBS sham stimulation(coil placed perpendicular to the skull),while the experimental group received upper limb rehabilitation robot training combined with iTBS real stimulation(coil placed parallel to the skull).Both groups underwent treatment for 3 weeks.Upper limb motor function was assessed using the Fugl-Meyer upper extremity(FMA-UE)scale and Wolf motor function test(WMFT);while neurological function was evaluated using the motor-evoked potentials(MEP)latency,amplitude,and central motor conduction time(CMCT)of the affected thumb abductor muscle.Activities of daily living were assessed using the modified Barthel index(MBI).Results(1)No significant differences in baseline data were found between the two groups(all P＞0.05).(2)Before treatment,the FMA-UE and WMFT scores in the experimental group were 27.48±7.87 and 28.22±3.87,respectively;and in the control group were 26.35±4.78 and 28.35±3.33,respectively;there were no significant differences in both FMA-UE and WMFT scores between the two groups(all P＞0.05).After 3weeks of treatment,the FMA-UE and WMFT scores in the experimental group were 40.35±8.96 and 37.74±4.11,respectively;and in the control group were 32.78±4.50 and 32.57±4.11,respectively;there were significant interaction effects of time and group(Ftime×group values of 19.613 and 31.522,both P＜0.01),main effects of group(Fgroup values of 5.401 and 5.897,both P＜0.05),and main effects of time(Ftime values of 176.516 and 211.478,both P＜0.01).(3)Before treatment,the MEP latency,amplitude,and CMCT in the experimental group were(24.39±3.56)ms,(137.77±42.67)μV,and(10.62±2.76)ms,respectively;and in the control group were(24.64±2.77)ms,(136.74±48.77)μV,and(10.73±1.84)ms,respectively,there were no significant differences between the two groups(all P＞0.05).After 3weeks of treatment,the MEP latency,amplitude,and CMCT in the experimental group were(20.39±1.83)ms,(239.91±43.70)μV,and(6.58±1.23)ms,respectively,and in the control group were(22.53±3.53)ms,(198.54±50.37)μV,and(9.19±1.60)ms,respectively,there were significant interaction effects of time and group(Ftime×group values of 7.270,15.554,and 20.110,all P＜0.05)and main effects of time(Ftime values of 76.540,256.706,and 100.629,all P＜0.01),the main effect of group for CMCT was significant(Fgroup=7.406,P＜0.01),but there were no significant difference in the main effect of group on MEP latency,amplitude between two groups(Fgroup values of 2.145,2.778,both P＞0.05).(4)Before treatment,the MBI score in the experimental group was 42.83±7.36,and in the control group was 43.91±6.56,with no significant difference between two groups(P＞0.05).After 3 weeks of treatments,the MBI score in the experimental group was 67.83±12.69,and in the control group was 54.13±5.57,there were significant interaction effects of time and group(Ftime×group=39.862,P＜0.01),main effects of group(Fgroup=8.083,P=0.007),and main effects of time(Ftime=226.241,P＜0.01).Conclusions Upper limb rehabilitation robot training combined with iTBS can improve upper limb motor function and neurological function and enhance the daily living activity ability of stroke patients.Real iTBS combined with robot training has a more significant effect than sham iTBS.

Objective:To investigatethe effects of different blood lead levels on indicators of immune function in occupationally lead-exposed populations.Methods:From October to December 2023, a total of 126 occupationally exposed lead workers of a company in Guizhou Province were selected, and their basic information was collected through questionnaires. Inductively coupled plasma mass spectrometry was used to detect blood lead levels in the study population. Workers were categorized into Group 1, Group 2 and Group 3 based on blood lead levels (blood lead levels <200 μg/L, 200~400 μg/L and >400 μg/L). Lymphocyte subpopulation marker leukocyte differentiation antigen (CD) in peripheral blood and interleukin (IL) -1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17, tumor necrosis factor-alpha (TNF-α), and interferon (IFN) -γ in serum were examined by flow cytometry. Serum levels of immunoglobulin (Ig) A, IgG, IgM, and complement proteins (C3, C4) were measured by immunoscattering turbidimetry. Data were statistically analyzed using rank sum test, Chi-square test or Fisher exact probability method for multiple samples.Results:Compared with group 1, the percentage of CD3 +CD8 + and CD4 +CD25 + cells decreased ( P<0.05) and the percentage of CD4 + CD95 + cells increased in the lead-exposed populations in groups 2 and 3 ( P<0.05) ; however, the serum IL-1β, IL-2, IL- 5, IL-8, IL-12p70, and IFN-γ levels were decreased ( P<0.05) in group 3. Meanwhile, IgG ( P<0.05) and IgM levels in serum of lead-exposed population in group 2 and group 3 were reduced ( P<0.05) comparing with group 1. Spearman correlation analysis showed that blood lead levels of workers were negatively correlated with the percentage of peripheral blood CD8 +CD95 + cells, CD3 +CD8 + cells, CD3 -CD16 + CD56 + cells, IgG, IgM, and IgA ( rs=-0.20, -0.22, -0.23, -0.24, -0.26, -0.35, P<0.05), but was positively correlated with the level of CD3 +CD4 + cells ( rs= 0.18, P<0.05). Regression analysis revealed that blood lead level was a risk factor for the percentage of CD8 +CD95 + cells, CD3 +CD8 + cells, CD3 -CD16 + CD56 + cells, IgG, IgM, and IgA ( P<0.05) . Conclusion:Different lead loads can lead to abnormal changes in peripheral blood lymphocyte subsets, cytokines, and immunoglobulin levels in occupationally lead-exposed people. Lead exposure in occupationally lead-exposed populations may affect their immune function.

This study was aimed at identifying the pathogenic bacteria responsible for the death of a young tiger at the Fujian Meihua Mountain South China Tiger Breeding Research Institute.Tissue samples from the lungs,liver,and intestines of the deceased tiger were collected,and the bacteria were cultured inasterile environment.The bacterial strains were characterized according to their morphological and molecular biological properties,including assessment of virulence genes and antibiotic resistance genes,mouse lethality tests,and antibiotic susceptibility evaluations.A predominant bacterial strain isolated from the liver of the deceased tiger was identified as enterotoxigenic Escherichia coli(ETEC)strain Tiger22513F.Phylogenetic analysis of the 16S rRNA gene revealed that the Tiger22513F strain exhibited close genetic similarity to the reference strain ETEC(MF919609.1),with 99.9%nucleotide similarity,and resided on the same evolutionary branch.The Tiger22513F strain contained 11 antibiotic resistance genes(tetA,sul1,sul3,cmlA,floR,blaTEM,blaSHV,blaCMY-2,qnrA,qnrS,and qnrD)along with five virulence genes(VT1,fyuA,tsh,iucD,and ST).Mouse lethality tests indicated significant pathogenicity toward mice,affecting primarily the lungs,liver,and intestines.Antibiotic susceptibility testing demonstrated that this strain exhibited resistance to various classes of beta-lactam antibiotics,as well as quinolones and aminoglycosides.This investigation successfully isolated a multi-drug resistant enterotoxigenic Escherichia coli strain with pronounced pathogenicity from the liver of a deceased tiger;thus providing valuable scientific insights for clinical diagnosis,as well as prevention and control measures,against ETEC infections in South China tigers.

This study was aimed at identifying the pathogenic bacteria responsible for the death of a young tiger at the Fujian Meihua Mountain South China Tiger Breeding Research Institute.Tissue samples from the lungs,liver,and intestines of the deceased tiger were collected,and the bacteria were cultured inasterile environment.The bacterial strains were characterized according to their morphological and molecular biological properties,including assessment of virulence genes and antibiotic resistance genes,mouse lethality tests,and antibiotic susceptibility evaluations.A predominant bacterial strain isolated from the liver of the deceased tiger was identified as enterotoxigenic Escherichia coli(ETEC)strain Tiger22513F.Phylogenetic analysis of the 16S rRNA gene revealed that the Tiger22513F strain exhibited close genetic similarity to the reference strain ETEC(MF919609.1),with 99.9%nucleotide similarity,and resided on the same evolutionary branch.The Tiger22513F strain contained 11 antibiotic resistance genes(tetA,sul1,sul3,cmlA,floR,blaTEM,blaSHV,blaCMY-2,qnrA,qnrS,and qnrD)along with five virulence genes(VT1,fyuA,tsh,iucD,and ST).Mouse lethality tests indicated significant pathogenicity toward mice,affecting primarily the lungs,liver,and intestines.Antibiotic susceptibility testing demonstrated that this strain exhibited resistance to various classes of beta-lactam antibiotics,as well as quinolones and aminoglycosides.This investigation successfully isolated a multi-drug resistant enterotoxigenic Escherichia coli strain with pronounced pathogenicity from the liver of a deceased tiger;thus providing valuable scientific insights for clinical diagnosis,as well as prevention and control measures,against ETEC infections in South China tigers.

Objective To investigate the therapeutic effects of upper limb rehabilitation robot training combined with intermittent theta burst stimulation(iTBS)on upper limb motor and neurological function in stroke patients with hemiplegia.Methods This study retrospectively consecutive enrolled 46 stroke hemiparetic patients from the Department of Rehabilitation Medicine,Nanjing Pukou People's Hospital.The patients were randomly assigned to a control group and an experimental group(23patients in each)using a random number table.Baseline data,including sex,age,disease duration,side of hemiplegia,and stroke type,were collected from patients enrolled.All patients received conventional treatment.The control group received upper limb rehabilitation robot training combined with iTBS sham stimulation(coil placed perpendicular to the skull),while the experimental group received upper limb rehabilitation robot training combined with iTBS real stimulation(coil placed parallel to the skull).Both groups underwent treatment for 3 weeks.Upper limb motor function was assessed using the Fugl-Meyer upper extremity(FMA-UE)scale and Wolf motor function test(WMFT);while neurological function was evaluated using the motor-evoked potentials(MEP)latency,amplitude,and central motor conduction time(CMCT)of the affected thumb abductor muscle.Activities of daily living were assessed using the modified Barthel index(MBI).Results(1)No significant differences in baseline data were found between the two groups(all P＞0.05).(2)Before treatment,the FMA-UE and WMFT scores in the experimental group were 27.48±7.87 and 28.22±3.87,respectively;and in the control group were 26.35±4.78 and 28.35±3.33,respectively;there were no significant differences in both FMA-UE and WMFT scores between the two groups(all P＞0.05).After 3weeks of treatment,the FMA-UE and WMFT scores in the experimental group were 40.35±8.96 and 37.74±4.11,respectively;and in the control group were 32.78±4.50 and 32.57±4.11,respectively;there were significant interaction effects of time and group(Ftime×group values of 19.613 and 31.522,both P＜0.01),main effects of group(Fgroup values of 5.401 and 5.897,both P＜0.05),and main effects of time(Ftime values of 176.516 and 211.478,both P＜0.01).(3)Before treatment,the MEP latency,amplitude,and CMCT in the experimental group were(24.39±3.56)ms,(137.77±42.67)μV,and(10.62±2.76)ms,respectively;and in the control group were(24.64±2.77)ms,(136.74±48.77)μV,and(10.73±1.84)ms,respectively,there were no significant differences between the two groups(all P＞0.05).After 3weeks of treatment,the MEP latency,amplitude,and CMCT in the experimental group were(20.39±1.83)ms,(239.91±43.70)μV,and(6.58±1.23)ms,respectively,and in the control group were(22.53±3.53)ms,(198.54±50.37)μV,and(9.19±1.60)ms,respectively,there were significant interaction effects of time and group(Ftime×group values of 7.270,15.554,and 20.110,all P＜0.05)and main effects of time(Ftime values of 76.540,256.706,and 100.629,all P＜0.01),the main effect of group for CMCT was significant(Fgroup=7.406,P＜0.01),but there were no significant difference in the main effect of group on MEP latency,amplitude between two groups(Fgroup values of 2.145,2.778,both P＞0.05).(4)Before treatment,the MBI score in the experimental group was 42.83±7.36,and in the control group was 43.91±6.56,with no significant difference between two groups(P＞0.05).After 3 weeks of treatments,the MBI score in the experimental group was 67.83±12.69,and in the control group was 54.13±5.57,there were significant interaction effects of time and group(Ftime×group=39.862,P＜0.01),main effects of group(Fgroup=8.083,P=0.007),and main effects of time(Ftime=226.241,P＜0.01).Conclusions Upper limb rehabilitation robot training combined with iTBS can improve upper limb motor function and neurological function and enhance the daily living activity ability of stroke patients.Real iTBS combined with robot training has a more significant effect than sham iTBS.

Objective:To investigatethe effects of different blood lead levels on indicators of immune function in occupationally lead-exposed populations.Methods:From October to December 2023, a total of 126 occupationally exposed lead workers of a company in Guizhou Province were selected, and their basic information was collected through questionnaires. Inductively coupled plasma mass spectrometry was used to detect blood lead levels in the study population. Workers were categorized into Group 1, Group 2 and Group 3 based on blood lead levels (blood lead levels <200 μg/L, 200~400 μg/L and >400 μg/L). Lymphocyte subpopulation marker leukocyte differentiation antigen (CD) in peripheral blood and interleukin (IL) -1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17, tumor necrosis factor-alpha (TNF-α), and interferon (IFN) -γ in serum were examined by flow cytometry. Serum levels of immunoglobulin (Ig) A, IgG, IgM, and complement proteins (C3, C4) were measured by immunoscattering turbidimetry. Data were statistically analyzed using rank sum test, Chi-square test or Fisher exact probability method for multiple samples.Results:Compared with group 1, the percentage of CD3 +CD8 + and CD4 +CD25 + cells decreased ( P<0.05) and the percentage of CD4 + CD95 + cells increased in the lead-exposed populations in groups 2 and 3 ( P<0.05) ; however, the serum IL-1β, IL-2, IL- 5, IL-8, IL-12p70, and IFN-γ levels were decreased ( P<0.05) in group 3. Meanwhile, IgG ( P<0.05) and IgM levels in serum of lead-exposed population in group 2 and group 3 were reduced ( P<0.05) comparing with group 1. Spearman correlation analysis showed that blood lead levels of workers were negatively correlated with the percentage of peripheral blood CD8 +CD95 + cells, CD3 +CD8 + cells, CD3 -CD16 + CD56 + cells, IgG, IgM, and IgA ( rs=-0.20, -0.22, -0.23, -0.24, -0.26, -0.35, P<0.05), but was positively correlated with the level of CD3 +CD4 + cells ( rs= 0.18, P<0.05). Regression analysis revealed that blood lead level was a risk factor for the percentage of CD8 +CD95 + cells, CD3 +CD8 + cells, CD3 -CD16 + CD56 + cells, IgG, IgM, and IgA ( P<0.05) . Conclusion:Different lead loads can lead to abnormal changes in peripheral blood lymphocyte subsets, cytokines, and immunoglobulin levels in occupationally lead-exposed people. Lead exposure in occupationally lead-exposed populations may affect their immune function.