Objective:To analyze the clinical and prognostic characteristics of patients with immune checkpoint inhibitor (ICI) -related colitis.Methods:A retrospective observational research method was conducted. Clinical data from patients diagnosed with ICI-related colitis at Beijing Friendship Hospital between January 2016 and May 2024 were collected. Clinical severity was assessed using the common terminology criteria for adverse event (CTCAE) grading, Mayo Score, Truelove & Witts Score, and endoscopic severity was assessed using Mayo endoscopic score (MES), ulcerative colitis endoscopic index of severity (UCEIS), and MD Anderson Cancer Center endoscopic inflammation grading (MD grading). Spearman rank correlation analysis was performed to evaluate the correlation between different scoring systems.Results:A total of 15 patients were included, with 10 males and 5 females, and the median age was 64.0 (55.5, 71.0) years. Thirteen patients were treated with programmed cell death protein 1 (PD-1) monoclonal antibodies, and 2 patients were treated with programmed cell death-ligand 1 (PD-L1) monoclonal antibodies. The median onset time of the 15 patients was 66.5 (41.0, 168.0) days after ICI treatment. All patients had diarrhea, only 25% patients presented with abdominal pain, and 20%-33% patients had fever, abdominal distension, nausea, and vomiting. Most of the inflammatory indicators were non-specific. Among the 14 patients who underwent CT examinations, 2 patients had no abnormal manifestations, 10 patients had left colon involvement, mainly manifested as thickening of the colon wall, and 6 of these patients had full-thickness involvement. Among the 12 patients who underwent colonoscopy examination, except for one patient with no abnormalities, 11 patients had rectal and sigmoid colon involvement, the proportions of the descending colon, ascending colon, and terminal ileum involvement decreased successively, and the involved mucosa was mainly manifested as disappearance of vascular texture, mucosal congestion and edema, erosion to shallow ulcers, and lumen stenosis. The lesions in 5 patients were distributed continuously similar to ulcerative colitis, and the lesions in 6 patients were distributed segmentally, 1 of them had an isolated deep ulcer in the rectum under endoscopy. Correlation analysis revealed significant correlations between endoscopic scores (MES, UCEIS, and MD grading; all P < 0.001). Truelove & Witts score strongly correlated with the Mayo score ( ρ = 0.88, P < 0.001). Among clinical-endoscopic comparisons, the Mayo score exhibited the strong positive correlation with endoscopic scores (all P < 0.05), followed by the Truelove & Witts score (all P < 0.05), and CTCAE diarrhea grading only had positive correlation with MD grading ( P = 0.034). However, CTCAE colitis grading showed no significant correlation with endoscopic scores (all P > 0.05). During a mean follow-up of 13.5 months, 10 patients received corticosteroid therapy, and 5 received alternative treatments. Corticosteroid-treated patients showed favorable clinical responses, and rapid tapering feasible occurred in parts of mild-to-moderate patients without relapse. However, perforation occurred in 2 patients with small bowel involvement. Conclusions:The main clinical manifestations of patients with ICI-related colitis are diarrhea. Imaging studies suggest thickening of the colonic wall. Endoscopic findings show the highest involvement in the left colon. Truelove&Witts score and Mayo score is strongly correlated. Corticosteroid therapy exhibits a rapid response, and the prognosis of patients with small intestine involvement is poor.

OBJECTIVE: To investigate the effect and mechanism of Hyssopus cuspidatus Boriss. extract (HCE) in ovalbumin (OVA)-induced allergic asthma. METHODS: Components identification of HCE was conducted using ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry. Mice were sensitized with OVA to establish asthmatic model, and dexamethasone was used as positive control. Respiratory reactivity, white cells counting in bronchoalveolar lavage fluid and peripheral blood, cytokine level measurement in serum and lung tissue, and histologic examination were performed to evaluate the therapeutic effect of HCE on asthma. Network pharmacology approach was used for mechanism prediction. Western blotting and untargeted lipidomics method were applied for mechanism validation. RESULTS: Fifty-two compounds were identified in HCE, predominantly terpenoids and flavonoids. HCE markedly reduced airway resistance, the eosinophil infiltration in lung tissues, and the levels of immunoglobulin E, interleukin-4, interleukin-5, and interleukin-13. Network pharmacology analysis suggested phosphatidylinositol 3-kinases (PI3K), c-Jun N-terminal kinase (JNK), and p38 Mitogen-activated protein kinase (p38 MAPK) may be key proteins of HCE in the treatment of allergic asthma. Western blot results indicated that the levels of phosphorylated PI3K, JNK, and P38 were downregulated in HCE-treated group. Moreover, HCE significantly upregulated the levels of ceramide and sphingomyelin and downregulated the level of phosphatidylcholine. CONCLUSION HCE inhibited allergic asthma via PI3K/JNK/P38 signaling pathway and lipid homeostasis regulation.

Objective:To analyze the clinical and prognostic characteristics of patients with immune checkpoint inhibitor (ICI) -related colitis.Methods:A retrospective observational research method was conducted. Clinical data from patients diagnosed with ICI-related colitis at Beijing Friendship Hospital between January 2016 and May 2024 were collected. Clinical severity was assessed using the common terminology criteria for adverse event (CTCAE) grading, Mayo Score, Truelove & Witts Score, and endoscopic severity was assessed using Mayo endoscopic score (MES), ulcerative colitis endoscopic index of severity (UCEIS), and MD Anderson Cancer Center endoscopic inflammation grading (MD grading). Spearman rank correlation analysis was performed to evaluate the correlation between different scoring systems.Results:A total of 15 patients were included, with 10 males and 5 females, and the median age was 64.0 (55.5, 71.0) years. Thirteen patients were treated with programmed cell death protein 1 (PD-1) monoclonal antibodies, and 2 patients were treated with programmed cell death-ligand 1 (PD-L1) monoclonal antibodies. The median onset time of the 15 patients was 66.5 (41.0, 168.0) days after ICI treatment. All patients had diarrhea, only 25% patients presented with abdominal pain, and 20%-33% patients had fever, abdominal distension, nausea, and vomiting. Most of the inflammatory indicators were non-specific. Among the 14 patients who underwent CT examinations, 2 patients had no abnormal manifestations, 10 patients had left colon involvement, mainly manifested as thickening of the colon wall, and 6 of these patients had full-thickness involvement. Among the 12 patients who underwent colonoscopy examination, except for one patient with no abnormalities, 11 patients had rectal and sigmoid colon involvement, the proportions of the descending colon, ascending colon, and terminal ileum involvement decreased successively, and the involved mucosa was mainly manifested as disappearance of vascular texture, mucosal congestion and edema, erosion to shallow ulcers, and lumen stenosis. The lesions in 5 patients were distributed continuously similar to ulcerative colitis, and the lesions in 6 patients were distributed segmentally, 1 of them had an isolated deep ulcer in the rectum under endoscopy. Correlation analysis revealed significant correlations between endoscopic scores (MES, UCEIS, and MD grading; all P < 0.001). Truelove & Witts score strongly correlated with the Mayo score ( ρ = 0.88, P < 0.001). Among clinical-endoscopic comparisons, the Mayo score exhibited the strong positive correlation with endoscopic scores (all P < 0.05), followed by the Truelove & Witts score (all P < 0.05), and CTCAE diarrhea grading only had positive correlation with MD grading ( P = 0.034). However, CTCAE colitis grading showed no significant correlation with endoscopic scores (all P > 0.05). During a mean follow-up of 13.5 months, 10 patients received corticosteroid therapy, and 5 received alternative treatments. Corticosteroid-treated patients showed favorable clinical responses, and rapid tapering feasible occurred in parts of mild-to-moderate patients without relapse. However, perforation occurred in 2 patients with small bowel involvement. Conclusions:The main clinical manifestations of patients with ICI-related colitis are diarrhea. Imaging studies suggest thickening of the colonic wall. Endoscopic findings show the highest involvement in the left colon. Truelove&Witts score and Mayo score is strongly correlated. Corticosteroid therapy exhibits a rapid response, and the prognosis of patients with small intestine involvement is poor.

Objective To elucidate the prediction ability of monocyte monolayer assay(MMA)used in hemolytic dis-ease of fetus and newborn(HDFN)caused by IgG anti-M.Methods Plasma from eight pregnant women containing IgG an-ti-M were collected,and were divided into two groups(4 cases with HDFN,with severe clinical symptoms such as fetal hy-drops,and 4 cases without HDFN)according to the clinical outcomes.M antigen positive cells were sensitized with dithioth-reitol(DTT)treated plasma from eight pregnant women respectively.MMA was performed by coincubation with monocytes and sensitized M cells,along with negative and positive control set up.T-test was conducted to compare the difference in phagocytic efficiency between two groups.Results The phagocytic efficiency in group with HDFN were 15.37%,13.05%,9.17%and 24.50%respectively,with the mean value of 15.52%,while the group without HDFN were 8.74%,11.07%,5.12%and 6.23%respectively,with the mean value of 7.79%.There was no significant difference in phagocytic efficiency between two groups(P>0.05).The mean values of both groups were not significantly different from the negative control(P>0.05),but both were significantly lower than positive control(P<0.05).Conclusion The low phagocytic efficiency couldn't convince that the MMA is an effective predictor for the HDFN caused by IgG anti-M,indicating that another mech-anism might be responsible for it rather than monocyte phagocytosis.The assessment of the peak systolic velocity in middle cerebral artery of the fetal should be considered in the management for pregnant women who produce IgG anti-M to estimate the situation of fetal anemia.

ObjectiveTo investigate the effect of modified Weijingtang on the pyroptosis of RAW264.7 macrophages via the cysteinyl aspartate-specific protease-1 （Caspase-1）/gasdermin D （GSDMD） pathway. MethodLipopolysaccharide （LPS） was used to induce pyroptosis of RAW264.7 cells. The blank group was treated with the blank serum， and the intervention groups were treated with the sera containing different doses of modified Weijingtang. After 24 h， the viability of cells in different groups was examined by the cell counting kit-8 （CCK-8）. The pyroptosis and morphology of cells in each group were observed by a scanning electron microscope and a phase-contrast microscope， respectively. The mRNA and protein levels of nucleotide-binding oligomerization domain-like receptor protein 3 （NLRP3）， Caspase-1， and GSDMD in each group were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. The levels of interleukin （IL）-18 and IL-1β in each group were measured by enzyme-linked immunosorbent assay. ResultUnder the electron microscope， RAW264.7 cells presented the best morphology and structure in the blank group and obvious pyroptosis and leakage of cell contents in the model （LPS） group. Compared with the model group， the intervention groups showed reduced pyroptosis to varying degrees， and the high-dose group had the closest cell morphology and structure to the blank group. Under the optical microscope， RAW264.7 cells were spherical in the blank group and irregular with protrusions in the model group. Compared with the model group， the intervention groups showed improved cell morphology， and the cell morphology in the group with the dose of 20% was the closest to that in the blank group. The mRNA and protein levels of NLRP3， Caspase-1， and GSDMD in the model group were higher than those in the blank group （P<0.05）. Compared with the model group， each intervention group showed down-regulated expression of the above indicators （P<0.05）. Compared with the blank group， the model group presented elevated levels of IL-18 and IL-1β （P<0.05）， which were lowered in the intervention （10%， 20%） groups （P<0.01）. ConclusionModified Weijingtang inhibits the pyroptosis of macrophages by down-regulating the Caspase-1/GSDMD pathway and reducing the release of proinflammatory cytokines.

Objective:To investigate the etiological characteristics of hand, foot and mouth disease (HFMD) and the VP1 gene evolution of coxsackievirus A6 (CVA6) in Qingdao from 2020 to 2022.Methods:Total enterovirus (EV), enterovirus 71 (EV71), coxsackievirus A16 (CVA16), CVA6 and coxsackievirus A10 (CVA10) were detected by fluorescent RT-PCR in throat swab samples from HFMD patients in Qingdao from 2020 to 2022. The full-length sequence amplification of VP1 gene and gene sequence determination of CVA6 isolates were performed, and the phylogenetic and molecular characteristics were analyzed by MEGA-X software.Results:The overall positive rate of enteroviruses in 1 645 samples collected during 2020-2021 was 80.73%(1 328/1 645). The proportions of EV71, CVA16, CVA6, CVA10 and other enteroviruses were 0.08%(1/1 328), 19.65%(261/1 328), 68.15%(905/1 328), 0.98%(13/1 328) and 11.14%(148/1 328), respectively. Children under 5 years old accounted for 75.68% (1 245/1 645) of all cases and 100% (2/2) of severe cases. A phylogenetic tree was constructed based on the VP1 region sequences of 45 CVA6 strains showing all strains belonging to the D3a subtype. There were 10 non-synonymous mutations of amino acids in the VP1 protein by gene evolution analysis.Conclusions:CVA6 D3a subtype is the main epidemic strain causing HFMD in Qingdao from 2020 to 2022, especially in children under 5 years old.

Humans ; Hypertension ; Atherosclerosis ; Colorectal Neoplasms ; Risk Factors

In the context of non-alcoholic fatty liver disease (NAFLD), characterized by dysregulated lipid metabolism in hepatocytes, the quest for safe and effective therapeutics targeting lipid metabolism has gained paramount importance. Sanhuang Xiexin Tang (SXT) and Baihu Tang (BHT) have emerged as prominent candidates for treating metabolic disorders. SXT combined with BHT plus Cangzhu (SBC) has been used clinically for Weihuochisheng obese patients. This retrospective analysis focused on assessing the anti-obesity effects of SBC in Weihuochisheng obese patients. We observed significant reductions in body weight and hepatic lipid content among obese patients following SBC treatment. To gain further insights, we investigated the effects and underlying mechanisms of SBC in HFD-fed mice. The results demonstrated that SBC treatment mitigated body weight gain and hepatic lipid accumulation in HFD-fed mice. Pharmacological network analysis suggested that SBC may affect lipid metabolism, mitochondria, inflammation, and apoptosis-a hypothesis supported by the hepatic transcriptomic analysis in HFD-fed mice treated with SBC. Notably, SBC treatment was associated with enhanced hepatic mitochondrial biogenesis and the inhibition of the c-Jun N-terminal kinase (JNK)/nuclear factor-kappa B (NF-κB) and extracellular signal-regulated kinase (ERK)/NF-κB pathways. In conclusion, SBC treatment alleviates NAFLD in both obese patients and mouse models by improving lipid metabolism, potentially through enhancing mitochondrial biogenesis. These effects, in turn, ameliorate inflammation in hepatocytes.
Humans ; Mice ; Animals ; Non-alcoholic Fatty Liver Disease/metabolism* ; NF-kappa B/metabolism* ; Organelle Biogenesis ; Retrospective Studies ; Mice, Inbred C57BL ; Obesity/metabolism* ; Liver ; Inflammation/metabolism* ; Body Weight ; Lipid Metabolism ; Lipids ; Diet, High-Fat/adverse effects*

Objective:To summarize the scope of research status and progress of midway abandonment of electronic health records.Methods:Articles on the application of community electronic health records were retrieved through computers in China Biology Medicine disc, Wanfang Data, China National Knowledge Infrastructure, PubMed. The retrieval time limit was from January 1, 2010 to June 1, 2022. The basic features of the articles were retrieved, screened and extracted independently by 2 researchers.Results:A total of 19 articles were included. The influencing factors of midway abandonment of electronic health records included 4 categories, namely the imbalance of perceived and actual learning costs and benefits, exposure to undesirable content during participation in electronic health records community, concerns about privacy infringement, demographic and sociological characteristics of users.Conclusions:The imbalance of perceived and actual learning costs and benefits, exposure to undesirable content during participation in electronic health records community, concerns about privacy infringement, and demographic and sociological characteristics of users can lead users abandon electronic health records. Relevant departments should pay attention to the needs of users, strengthen information supervision and privacy protection, formulate appropriate health education programs, standardize the electronic health records management process, so as to improve the utilization rate of electronic health records.

【Objective】 To establish an experimental method for detecting phagocytosis of sensitized red blood cells in vitro by flow cytometry. 【Methods】 Mononuclear cells were isolated from the peripheral blood of blood donors and cultured in a cell incubator for 1 hour, and then adherent monocytes were isolated and obtained. Di^b-positive red blood cells (RBCs) were labeled with PKH26 and then sensitized with IgG anti-Di^b. The sensitized RBCs were added to monocytes for in vitro phagocytosis assay. Monocytes were labeled with FITC anti-human CD14, then phagocytosis was measured by flow cytometry, and the phagocytic efficiency was calculated. The method was used to detect the phagocytic efficiency of monocytes on human IgG anti-D sensitized RBCs with different titers. 【Results】 The phagocytic efficiency of monocytes was averaged at 5% (1.2%~7.6%, SD 3.30) versus 81% (71.4%~92.7%, SD 8.65) in the negative versus positive control group, respectively. Phagocytic activity of monocytes mediated by anti-D was correlated with the antibody titer. The phagocytosis efficiency was within 10% when the antibody titer was lower than 32 and increased sharply when the titer was between 32 to 128, it entered a plateau and stabilized at 80% at the titer above 256. 【Conclusion】 A detection platform for detecting phagocytosis-sensitized RBCs in vitro by flow cytometry has been successfully established. It can be used to assess the clinical significance of red blood cell allotype or autologous IgG antibodies.