ObjectiveThis study aims to explore and elucidate the possible mechanism of action of Shakuyakukanzoto (SKT) in improving ulcerative colitis (UC) in mice through regulating energy metabolism and polarization of macrophages. MethodsThe mouse UC model was constructed by administering 3% dextran sulfate sodium salt (DSS), and the mice were treated with SKT intragastrically. In addition, single-cell sequencing and enrichment of metabolic pathways against two datasets, GSE21157 and GSE210415, were conducted first. Second, the extraction and metabolomics of peritoneal macrophages from UC mice were verified. Then, the pathway of differentially abundant metabolite enrichment and the correlation of UC risk were analyzed depending on univariate Mendelian randomization of two samples weighted by standard inverse variance. Finally, the results were verified by qRT-PCR, Western blot, and flow cytometry. ResultsAccording to the HE staining results, SKT can significantly alleviate colon damage caused by DSS. Macrophages, NK cells, T cells, and more than 10 different types of cells, based on single-cell sequencing analysis, are detected in the intestinal wall. In the disease group, we can conclude that the activity of 49 macrophage metabolic pathways, mainly involved in energy metabolism, is significantly upregulated through a comparison of the two datasets. In energy metabolomics, 10 and 18 types of metabolites accompanied by significantly upregulated and downregulated differential expression were identified in the treatment group and the model group, as well as the model group and the blank group, respectively. Meanwhile, these differentially expressed metabolites present an obvious correlation with glycolysis and oxidative phosphorylation. Moreover, it can be inferred that glycolysis and the oxidative phosphorylation-related gene NDUFS1 (OR: 0.56, 95% CI: 0.48-0.98, P=0.000 068) are associated with a reduced risk of UC based on the univariate Mendelian randomization of two samples weighted based on standard inverse variance. By analyzing the difference in transcription levels between the two datasets, the transcription level of NDUFS1 in UC was decreased compared with that in the normal group. The results of qRT-PCR, Western blot, and flow cytometry indicate that SKT can promote the expression of the oxidative phosphorylation protein NDUFS1 in macrophages and inhibit the M1-type polarization of macrophages. Furthermore, knockdown/overexpression of NDUFS1 can affect the effect of SKT on M1-type polarization of macrophages. ConclusionBased on the results of this study, SKT inhibits macrophage polarization toward the M1 phenotype by regulating the level of the oxidatively phosphorylated protein NDUFS1 in macrophages; hence, UC is also relieved in mice. These conclusions not only reveal the therapeutic mechanism of SKT for UC but also provide a new theoretical basis for clinical application.

Objective Bevacizumab has been clinically used in colorectal cancer,ovarian cancer,cervical cancer,non-small cell lung cancer and other tumor diseases.Common adverse reactions during bevacizumab treatment include albuminuria,thrombosis,bleeding,gastrointestinal perforation and hypertension,among which the incidence of hypertension is as high as 19％-47％.The occurrence of hypertension affects the quality of life of patients,hinds the normal development of tumor treatment,and even induces serious cardiovascular diseases and increases the risk of death,which requires clinical attention.In this paper,the mechanism,influencing factors,prognosis and related treatment of bevacizumab associated hypertension were reviewed,so as to provide reference for clinical rational drug use.

Objective Viral encephalitis is an infectious disease severely affecting human health.It is caused by a wide variety of viral pathogens,including herpes viruses,flaviviruses,enteroviruses,and other viruses.The laboratory diagnosis of viral encephalitis is a worldwide challenge.Recently,high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections.Thus,In this study,we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods We designed nine pairs of specific polymerase chain reaction(PCR)primers for the 12 viruses by reviewing the relevant literature.The detection ability of the primers was verified by software simulation and the detection of known positive samples.Amplicon sequencing was used to validate the samples,and consistency was compared with Sanger sequencing. Results The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×,and the sequence lengths were consistent with the sizes of the predicted amplicons.The sequences were verified using the National Center for Biotechnology Information BLAST,and all results were consistent with the results of Sanger sequencing. Conclusion Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis.It is also a useful tool for the high-volume screening of clinical samples.

As the backbone force of China's social and economic construction, the health status of workers is closely related to the nation's productivity and social development. Currently, cancers have become one of the major diseases threatening the health of workers. However, there are still many shortcomings in the cancer screening services for the workers. To standardize cancer screening services for workers, ensure the quality of screening services, and improve the overall screening effectiveness, 19 institutions, including Peking Union Medical College Hospital of the Chinese Academy of Medical Sciences, have jointly formulated the Group Standard "Specification for service of cancer screening for workers (T/CHAA 023-2023)". This standard follows the principles of "legality, scientific rigor, advancement, and feasibility" and combines the frontier scientific advances in cancer screening. It clarifies the relevant requirements for service principles, service design, service delivery, service management, service evaluation, and improving worker cancer screening. Implementing this group standard will help connect the common screening needs of workers, employers, and cancer screening service providers, standardize the screening process, improve screening quality, and ultimately increase the early diagnosis rate and survival rate of cancer patients. Consequently, this group standard will help safeguard workers' health rights and interests, ensure the labor force resources, promote the comprehensive coordinated and sustainable development of society, and contribute to realizing the "Healthy China 2030" strategic policy.

Objective:To assess the value of serum alpha-fetoprotein(AFP),protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ)and glypican-3(GPC-3)in the diagnosis of hepatocellular carcinoma(HCC).Methods:Studies of AFP,PIVKA-Ⅱ,GPC-3 or in combination for the diagnosis of HCC since 2002 were searched in PubMed,Web of Science and Embase databases.The literature was screened according to the inclusion and exclusion criteria,the quality of the included articles was evaluated by QUADAS checklist,and relevant data were extracted by Meta DiSc,Review Manager 5.4 and Stata 15.1.The diagnostic values of AFP,PIVKA-Ⅱ and GPC-3 alone or in combination for HCC were assessed with receiver operating characteristic(ROC)curve.Results:A total of 32 articles were included in the study.Meta-analysis showed that when a single marker was used to diagnose HCC,the area under the ROC curve(AUC)of PIVKA-Ⅱ was the highest(0.88,95%CI:0.85-0.91),followed by GPC-3 and AFP.The AUC of combination of serum markers was higher than that of a single marker,and the AUC of PIVKA-Ⅱ combined with GPC-3 was the highest(0.90,95%CI:0.87-0.92).When a single marker was used for diagnosis,the sensitivity of PIVKA-Ⅱ and GPC-3 were relatively high(0.75 and 0.76),while the specificity of PIVKA-Ⅱ(0.88)and AFP(0.87)were higher than that of GPC-3(0.81).The sensitivity of the combination of serum markers was higher than that of a single marker,while the specificity was not significantly improved.When a single marker is used to diagnose HCC,the diagnostic odds ratio(DOR)of PIVKA-Ⅱ was the highest(22,95%CI:13-36),followed by GPC-3 and AFP.The DOR of the combination of two markers in the diagnosis of HCC was higher than that of a single marker,and the DOR of AFP combined with GPC-3 was the highest(25,95%CI:9-67).The DOR of the combination of the three markers was significantly reduced to 10(95%CI:7-45).Conclusions:When a single marker is used,PIVKA-Ⅱhas a higher diagnostic value for HCC.The combination of two markers can significantly improve the diagnostic sensitivity,and AFP combined with PIVKA-Ⅱ is recommended for the diagnosis of HCC.The combination of all three markers failed to further improve the diagnostic value.

Objective To investigate the age-related changes of the mandibular third molar root pulp visibility in individuals in East China,and to explore the feasibility of applying this method to deter-mine whether an individual is 18 years or older.Methods A total of 1 280 oral panoramic images were collected from the 15-30 years old East China population,and the mandibular third molar root pulp visibility in all oral panoramic images was evaluated using OLZE 0-3 four-stage method,and the age distribution of the samples at each stage was analyzed using descriptive statistics.Results Stages 0,1,2 and 3 first appeared in 16.88,19.18,21.91 and 25.44 years for males and in 17.47,20.91,22.01 and 26.01 years for females.In all samples,individuals at stages 1 to 3 were over 18 years old.Conclusion It is feasible to determine whether an individual in East China is 18 years or older based on the mandibular third molar root pulp visibility on oral panoramic images.

UPLC-Q-Exactive-MS/MS and network pharmacology were employed to preliminarily study the active components and mechanism of Jinwugutong Capsules in the treatment of osteoporosis. Firstly, UPLC-Q-Exactive-MS/MS was employed to characterize the chemical components of Jinwugutong Capsules, and network pharmacology was employed to establish the "drug-component-target-pathway-disease" network. The key targets and main active components were thus obtained. Secondly, AutoDock was used for the molecular docking between the main active components and key targets. Finally, the animal model of osteoporosis was established, and the effect of Jinwugutong Capsules on the expression of key targets including RAC-alpha serine/threonine-protein kinase(AKT1), albumin(ALB), and tumor necrosis factor-alpha(TNF-α) was determined by enzyme-linked immunosorbent assay(ELISA). A total of 59 chemical components were identified from Jinwugutong Capsules, among which coryfolin, 8-prenylnaringenin, demethoxycurcumin, isobavachin, and genistein may be the main active components of Jinwugutong Capsules in treating osteoporosis. The topological analysis of the protein-protein interaction(PPI) network revealed 10 core targets such as AKT1, ALB, catenin beta 1(CTNNB1), TNF, and epidermal growth factor receptor(EGFR). The Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment showed that Jinwugutong Capsules mainly exerted the therapeutic effect by regulating the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT) signaling pathway, neuroactive ligand-receptor interaction, mitogen-activated protein kinase(MAPK) signaling pathway, Rap1 signaling pathway and so on. Molecular docking showed that the main active components of Jinwugutong Capsules well bound to the key targets. ELISA results showed that Jinwugutong Capsules down-regulated the protein levels of AKT1 and TNF-α and up-regulated the protein level of ALB, which preliminarily verified the reliability of network pharmacology. This study indicates that Jinwugutong Capsules may play a role in the treatment of osteoporosis through multiple components, targets, and pathways, which can provide reference for the further research.
Animals ; Tumor Necrosis Factor-alpha/genetics* ; Network Pharmacology ; Capsules ; Molecular Docking Simulation ; Phosphatidylinositol 3-Kinases ; Reproducibility of Results ; Tandem Mass Spectrometry

Objectives: To construct a nomogram for prediction of intrahepatic cholangiocarcinoma (ICC) lymph node metastasis based on inflammation-related markers,and to conduct its clinical verification. Methods: Clinical and pathological data of 858 ICC patients who underwent radical resection were retrospectively collected at 10 domestic tertiary hospitals in China from January 2010 to December 2018. Among the 508 patients who underwent lymph node dissection,207 cases had complete variable clinical data for constructing the nomogram,including 84 males,123 females,109 patients≥60 years old,98 patients<60 years old and 69 patients were pathologically diagnosed with positive lymph nodes after surgery. Receiver operating characteristic curve was drawn to calculate the accuracy of preoperative imaging examinations to determine lymph node status,and the difference in overall survival time was compared by Log-rank test. Partial regression squares and statistically significant preoperative variables were screened by backward stepwise regression analysis. R software was applied to construct a nomogram,clinical decision curve and clinical influence curve,and Bootstrap method was used for internal verification. Moreover,retrospectively collecting clinical information of 107 ICC patients with intraoperative lymph node dissection admitted to 9 tertiary hospitals in China from January 2019 to June 2021 was for external verification to verify the accuracy of the nomogram. 80 patients with complete clinical data but without lymph node dissection were divided into lymph node metastasis high-risk group and low-risk group according to the score of the nomogram among the 858 patients. Log-rank test was used to compare the overall survival of patients with or without lymph node metastasis diagnosed by pathology. Results: The area under the curve of preoperative imaging examinations for lymph node status assessment of 440 patients was 0.615,with a false negative rate of 62.8% (113/180) and a false positive rate of 14.2% (37/260). The median survival time of 207 patients used to construct a nomogram with positive or negative postoperative pathological lymph node metastases was 18.5 months and 27.1 months,respectively (P<0.05). Five variables related to lymph node metastasis were screened out by backward stepwise regression analysis,which were combined calculi,neutrophil/lymphocyte ratio,albumin,liver capsule invasion and systemic immune inflammation index,according to which a nomogram was constructed with concordance index(C-index) of 0.737 (95%CI: 0.667 to 0.806). The C-index of external verification was 0.674 (95%CI:0.569 to 0.779). The calibration prediction curve was in good agreement with the reference curve. The results of the clinical decision curve showed that when the risk threshold of high lymph node metastasis in the nomogram was set to about 0.32,the maximum net benefit could be obtained by 0.11,and the cost/benefit ratio was 1∶2. The results of clinical influence curve showed that when the risk threshold of high lymph node metastasis in the nomogram was set to about 0.6,the probability of correctly predicting lymph node metastasis could reach more than 90%. There was no significant difference in overall survival time between patients with high/low risk of lymph node metastasis assessed by the nomogram and those with pathologically confirmed lymph node metastasis or without lymph node metastasis (Log-rank test:P=0.082 and 0.510,respectively). Conclusion: The prediction accuracy of preoperative nomogram for ICC lymph node metastasis based on inflammation-related markers is satisfactory,which can be used as a supplementary method for preoperative diagnosis of lymph node metastasis and is helpful for clinicians to make personalized decision of lymph node dissection for patients with ICC.

Objective: To describe a technique of endoscopic transoral approach nasopharyngectomy for petroclival and jugular foramen nasopharyngeal carcinoma, based on anatomic studies and surgeries. Methods: Three dry human skulls and five fresh human cadaver heads were used for anatomic study of a endoscopic transoral approach to expose petroclival and jugular foramen. The anatomical landmarks and the extent of exposure were recorded. Six clinical cases who were treated in Eye & ENT Hospital, Fudan University from June 2020 to April 2022 were used to illustrate the technique and feasibility of this approach and to assess its indications and advantages, including 3 males and 3 females, aged 42 to 69 years old. Descriptive analysis was used in this research. Results: On the basis of the preservation of the internal pterygoid muscle and the external pterygoid muscle, this approach could fully expose the parapharyngeal, petrosal and paraclival segment internal carotid arteries, and safely deal with the lesions of jugular foramen and petroclival region. The 6 patients in our study tolerated the procedure well. Postoperative enhanced MRI showed complete resection of the tumor and no postoperative masticatory dysfunction. Conclusion: Endoscopic transoral approach is a safe, minimally invasive and effective surgical treatment for petroclival and jugular foramen recurrent nasopharyngeal carcinoma.
Male ; Female ; Humans ; Adult ; Middle Aged ; Aged ; Nasopharyngeal Carcinoma ; Jugular Foramina ; Neoplasm Recurrence, Local ; Endoscopy/methods* ; Nasopharyngeal Neoplasms/surgery*

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis