Objective To identify core targets of hepatocellular carcinoma (HCC) by using bioinformatics and specific algorithms, explore their relationships with immune cells, and investigate the causal relationships between immune cells and HCC through Mendelian randomization. Methods Relevant genes associated with the development of HCC were screened using the GEO and TCGA databases. Immune infiltration analysis was conducted using GSVA and CIBERSORT algorithms. A bidirectional Mendelian randomization analysis was then performed to explore the causal relationships between immune cells and HCC. Results A total of 284 HCC-related genes were identified, with 120 genes recognized within the protein interaction network. Immune infiltration analysis revealed significant correlations between key genes and immune cells. Mendelian randomization results indicated that HLA DR on CD33⁺ HLA DR⁺ CD14dim (OR=1.097, 95%CI: 1.002–1.201, P=0.045, P_Bonferroni=0.091) and CD8 on CD28⁺ CD45RA⁺ CD8⁺ T cell (OR=1.123, 95%CI: 1.027–1.228, P=0.011, P_Bonferroni=0.022) were the risk factors for HCC. Conversely, HLA DR⁺⁺ monocyte absolute count was identified as a protective factor for HCC (OR=0.812, 95%CI: 0.702–0.938, P=0.005, P_Bonferroni=0.139). Conclusion The occurrence and development of liver cancer may be related to CDK1, CCNB1, and CDC20, showing a high degree of correlation with Th2 cells, T helper cells, Th17 cells, and DCs. Mendelian randomization shows that HLA DR on CD33⁺HLA DR⁺ CD14dim and CD8 on CD28⁺CD45RA⁺CD8⁺T cells are associated with an increased risk of HCC. The risk of hepatocellular carcinoma is associated with a decrease in the level of HLA DR⁺⁺monocyte absolute count.

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: 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.

Accurate timing of myelination is crucial for the proper functioning of the central nervous system. Here, we identified a de novo heterozygous mutation in TMEM63A (c.1894G>A; p. Ala632Thr) in a 7-year-old boy exhibiting hypomyelination. A Ca²⁺ influx assay suggested that this is a loss-of-function mutation. To explore how TMEM63A deficiency causes hypomyelination, we generated Tmem63a knockout mice. Genetic deletion of TMEM63A resulted in hypomyelination at postnatal day 14 (P14) arising from impaired differentiation of oligodendrocyte precursor cells (OPCs). Notably, the myelin dysplasia was transient, returning to normal levels by P28. Primary cultures of Tmem63a^-/- OPCs presented delayed differentiation. Lentivirus-based expression of TMEM63A but not TMEM63A_A632T rescued the differentiation of Tmem63a^-/- OPCs in vitro and myelination in Tmem63a^-/- mice. These data thus support the conclusion that the mutation in TMEM63A is the pathogenesis of the hypomyelination in the patient. Our study further demonstrated that TMEM63A-mediated Ca²⁺ influx plays critical roles in the early development of myelin and oligodendrocyte differentiation.
Animals ; Cell Differentiation/physiology* ; Oligodendroglia/metabolism* ; Mice, Knockout ; Mice ; Male ; Myelin Sheath/metabolism* ; Humans ; Child ; Cells, Cultured ; Oligodendrocyte Precursor Cells/metabolism*

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

Solid organ transplantation has significantly prolonged the survival of patients with end-stage diseases. However, long-term use of immunosuppressants will increase the risk of post-transplantation diabetes mellitus (PTDM) in the recipients, thereby elevating the risk of infection, cardiovascular disease and death. In recent years, with persistent improvement of diagnostic criteria of PTDM, clinicians have deepened the understanding of this disease. Compared with type 2 diabetes mellitus, PTDM significantly differs in pathophysiological characteristics and clinical progression. Hence, different treatment strategies should be adopted. Early identification of risk factors of organ transplant recipients, early diagnosis and intervention are of significance for improving the quality of life of recipients, prolonging the survival of grafts and reducing the fatality of recipients. Therefore, the diagnosis, incidence and risk factors of PTDM were reviewed in this article, aiming to provide reference for clinicians to deliver prompt diagnosis and intervention for PTDM.

Objective:To analyze the epidemic characteristics of reported tuberculosis incidence in Kashgar from 2015 to 2022, and use the seasonal autoregressive integrated moving average (SARIMA) model to predict the incidence, providing references for the local control of pulmonary tuberculosis.Methods:The reported incidence data of tuberculosis in the Kashgar area of Xinjiang from January 2015 to August 2023 were collected through the"Infectious Disease Monitoring System", a subsystem of the "Chinese Disease Prevention and Control Information System". The epidemic characteristics of reported incidence in this area from 2015 to 2022 were analyzed. Two SARIMA models of monthly reported incidence number and rate were established. The prediction performance of the two models was evaluated using the reported incidence data of tuberculosis from January 2023 to August 2023. The χ2 test was used to analyze population characteristics, and the Cochran-Armitage trend test was used to analyze annual incidence. Results:From 2015 to 2022, 133 972 cases of pulmonary tuberculosis were reported in Kashgar, with a yearly reported incidence rate of 383.64/100 000, showing a rising trend ( TCA=77.03, P<0.001) and then a declining trend ( TCA=176.16, P<0.001). The proportion of pathogenic positive pulmonary tuberculosis had increased yearly ( TCA=132.66, P<0.001). The reported onset time was concentrated from January to June each year, with a peak in April. Yengisar County, Zepu County and Yopurga County had the highest reported incidence rate in Kashgar. The sex ratio of men to women was 1.03∶1, and the reported incidence rate of men was higher than that of women ( χ2=27.04, P<0.001). The reported incidence rate of the group aged 60 years and older was the highest. The patient′s occupation was mainly farmers (84.99%). The average relative errors of the SARIMA ( 1, 1, 2) ( 0, 1, 1) 12 model and SARIMA ( 0, 1, 1)( 0, 1, 1) 12 model in predicting the reported monthly incidence number and rate were 11.67% and -9.81%, respectively. Both models had good prediction accuracy (MAPE=33.55%, MAPE=38.22%). Conclusion:The average reported incidence rate of pulmonary tuberculosis in the Kashgar area shows a rising trend first and then a declining trend. The patients are mainly men and farmers, and attention should be paid to the prevention and control of tuberculosis among the elderly in winter and spring. The SARIMA ( 1, 1, 2) ( 0, 1, 1) 12 model and SARIMA ( 0, 1, 1)( 0, 1, 1) 12 model can fit the trend of reported tuberculosis incidence in the Kashgar area well and have good predictive performance.

Objective:To analyze the epidemic characteristics of reported tuberculosis incidence in Kashgar from 2015 to 2022, and use the seasonal autoregressive integrated moving average (SARIMA) model to predict the incidence, providing references for the local control of pulmonary tuberculosis.Methods:The reported incidence data of tuberculosis in the Kashgar area of Xinjiang from January 2015 to August 2023 were collected through the"Infectious Disease Monitoring System", a subsystem of the "Chinese Disease Prevention and Control Information System". The epidemic characteristics of reported incidence in this area from 2015 to 2022 were analyzed. Two SARIMA models of monthly reported incidence number and rate were established. The prediction performance of the two models was evaluated using the reported incidence data of tuberculosis from January 2023 to August 2023. The χ2 test was used to analyze population characteristics, and the Cochran-Armitage trend test was used to analyze annual incidence. Results:From 2015 to 2022, 133 972 cases of pulmonary tuberculosis were reported in Kashgar, with a yearly reported incidence rate of 383.64/100 000, showing a rising trend ( TCA=77.03, P<0.001) and then a declining trend ( TCA=176.16, P<0.001). The proportion of pathogenic positive pulmonary tuberculosis had increased yearly ( TCA=132.66, P<0.001). The reported onset time was concentrated from January to June each year, with a peak in April. Yengisar County, Zepu County and Yopurga County had the highest reported incidence rate in Kashgar. The sex ratio of men to women was 1.03∶1, and the reported incidence rate of men was higher than that of women ( χ2=27.04, P<0.001). The reported incidence rate of the group aged 60 years and older was the highest. The patient′s occupation was mainly farmers (84.99%). The average relative errors of the SARIMA ( 1, 1, 2) ( 0, 1, 1) 12 model and SARIMA ( 0, 1, 1)( 0, 1, 1) 12 model in predicting the reported monthly incidence number and rate were 11.67% and -9.81%, respectively. Both models had good prediction accuracy (MAPE=33.55%, MAPE=38.22%). Conclusion:The average reported incidence rate of pulmonary tuberculosis in the Kashgar area shows a rising trend first and then a declining trend. The patients are mainly men and farmers, and attention should be paid to the prevention and control of tuberculosis among the elderly in winter and spring. The SARIMA ( 1, 1, 2) ( 0, 1, 1) 12 model and SARIMA ( 0, 1, 1)( 0, 1, 1) 12 model can fit the trend of reported tuberculosis incidence in the Kashgar area well and have good predictive performance.

Objective:To analyze the impact of the implementation of the policy of centralized volume-based procurement of dental implant consumables on the prevention and control of corruption risk in public hospitals, and provide reference for improving the construction of corruption risk prevention and control in public hospitals.Methods:Develop a survey questionnaire for three entities: the Discipline Inspection Commission of public hospitals, dental implant doctors in public hospitals, and dental implant consumables distribution enterprises. The questionnaire content for the Discipline Inspection Commission of public hospitals mainly included the impact of the implementation of the policy of centralized volume-based procurement of dental implant consumables on the prevention and control of hospital integrity risks, as well as the development of supporting policies in hospitals; The questionnaire content for dental implant doctors mainly included their understanding of the centralized volume-based procurement policy, their communication with distribution companies, and their awareness of integrity; The questionnaire content for dental implant consumables distribution enterprises mainly included the situation of the distribution enterprises entering the centralized volume-based procurement catalog for implants, and the subsequent adjustment of business strategies.Using convenience sampling method, a questionnaire survey was conducted from February to June 2023 on the Discipline Inspection Commission of public hospitals in Zhejiang Province, dental implant doctors in public hospitals nationwide, and distribution enterprises of dental implant consumables in Zhejiang Province. Descriptive analysis was conducted on the questionnaire data.Results:Effectively collected 16 questionnaires filled out by the Discipline Inspection Commission leaders of public hospitals in Zhejiang Province. Among them, the Discipline Inspection Commission leaders of 11 public hospitals believed that the implementation of the policy of centralized volume-based procurement of dental implant consumables could reduce the existing corruption risks of public hospitals, 1 believed that it would create new corruption risks, and 4 believed that both aspects of the impact existed; 12 leaders believed that the policy′s strengthening of corruption risk prevention and control was mainly reflected in squeezing implant prices, reducing selection and procurement risks, and reducing red envelopes and kickbacks. 270 questionnaires from dental implant doctors in public hospitals were effectively collected. Regarding the implementation of the centralized volume-based procurement policy, 187 people believed that it would inhibit the development of the dental implant industry, 148 people expected their personal salaries to decrease, 78 people would participate more in lectures and training organized by enterprises, and 39 people would recommend implant systems outside the centralized volume-based procurement catalog to patients; 140 people were unable to accurately grasp all the contents of the " Nine Guidelines on Integrity for Staff of Medical Institution" ; Only 202 people believed that compliance contact with distribution companies could only be based on listening to their introduction to the implant system. 23 questionnaires were effectively collected from dental implant consumables distribution companies. Among them, 22 companies would reduce their expenses in maintaining relationships with clinical doctors after the implementation of the centralized procurement policy, and 14 companies would reduce their sales position expenses. All distribution companies believed that the phenomenon of medical institution staff receiving red envelopes and kickbacks would decrease or disappear after the implementation of the centralized volume-based procurement policy.Conclusions:The implementation of the policy of centralized volume-based procurement of dental implant consumables is beneficial for reducing the existing corruption risks in public hospitals, but if regulatory oversight is inadequate, new corruption risks will arise in the early stages of policy implementation. Public hospitals should improve the supporting system for centralized volume-based procurement of dental implant consumables, standardize the procurement process of dental implant consumables outside the centralized volume-based procurement catalog, strengthen supervision and inspection of centralized procurement, and further strengthen corruption risk prevention and control by implementing anti-corruption education.