ObjectiveTo observe the effects of modified Chaihu Shugansan on the calmodulin-dependent protein kinase Ⅱ（CaMKⅡ）/cAMP-response element binding protein （CREB） signaling pathway in the hippocampus and heart tissue of a rat model with myocardial ischemia and depression and explore the mechanism by which this formula prevents and treats coronary heart disease combined with depression. MethodsThe model of myocardial ischemia combined with depression was established by high-fat diet， intraperitoneal injection of isoproterenol （ISO）， and chronic unpredictable mild stress （CUMS）. A total of 108 SD male rats were randomly divided into normal group， model group， high （23.4 g·kg^-1）， medium （11.7 g·kg^-1）， and low （5.85 g·kg^-1） dose groups of modified Chaihu Shugansan， CaMKⅡ inhibitor （KN93） group， and KN93 + high， medium， and low dose groups of modified Chaihu Shugansan， with 12 rats in each group. From the first day of modeling to the end of modeling， drugs were administered once a day. In the seventh and eighth weeks， the KN93 group and the KN93 + high， medium， and low dose groups of modified Chaihu Shugansan were intraperitoneally injected with KN93 three times weekly. At the end of the eighth week， behavioral tests including sucrose preference， open field， and elevated plus maze were conducted. Electrocardiogram （ECG） lead Ⅱ changes were observed in each group of rats， and hematoxylin-eosin （HE） staining was performed to observe changes in heart tissue. Serum levels of triglycerides （TG）， total cholesterol （TC）， high-density lipoprotein （HDL）， low-density lipoprotein （LDL）， and lactate dehydrogenase （LDH） were measured by using an enzyme-labeled instrument. Creatine kinase （CK） and creatine kinase-MB （CK-MB） were detected by ultraviolet spectrophotometry， while serum monocyte chemoattractant protein-1 （MCP-1） was measured by enzyme-linked immunosorbent assay （ELISA）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect mRNA expression of CaMKⅡ and CREB in hippocampal and heart tissue， and Western blot was performed to assess protein expression of CaMKⅡ， phosphorylated （p）-CaMKⅡ， CREB， and p-CREB. ResultsCompared to the normal group， the model group showed significant reductions in sucrose preference rate， total activity distance in the open field， number of entries into the center area of the open field， and percentage of entries into the open arms of the elevated plus maze （P<0.01）. The ECG showed ST-segment elevation， and HE staining showed serious degeneration of myocardial fibers， disordered arrangement， and infiltration of a large number of inflammatory cells. In addition， serum TC and LDL levels increased （P<0.01）， and HDL level decreased （P<0.01）. CK， CK-MB， LDH， and MCP-1 levels significantly increased （P<0.05， P<0.01）. The mRNA expression of CaMKⅡ and CREB and the protein expression of p-CaMKⅡ and p-CREB decreased in the hippocampal tissue （P<0.05， P<0.01）， but those increased in the heart tissue （P<0.01）. Compared to the model group， the high， medium， and low dose groups of modified Chaihu Shugansan showed improvements in these abnormalities. The KN93 group had reduced sucrose preference， total activity distance in the open field， number of entries into the center area of the open field， and percentage of entries into the open arms of the elevated plus maze （P<0.01）， as well as decreased serum CK， CK-MB， LDH， and MCP-1 levels （P<0.05， P<0.01）. KN93 also reduced ST-segment elevation， alleviated the degeneration degree of myocardial fibrosis， and lowered inflammatory cell infiltration. The mRNA expression of CaMKⅡ and CREB and the protein expression of p-CaMKⅡ and p-CREB in both the hippocampal and heart tissue were reduced （P<0.05， P<0.01）. The KN93 + high， medium， and low dose groups of modified Chaihu Shugansan showed further improvements in these abnormalities compared to the KN93 group. ConclusionThe modified Chaihu Shugansan exerts antidepressant and myocardial protective effects in rats with myocardial ischemia and depression， possibly related to bidirectional regulation of the CaMKⅡ/CREB signaling pathway， with the high-dose modified Chaihu Shugansan showing the best effects.

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

Objective: To investigate the characteristics and risk factors of an outbreak of acute hemorrhagic conjunctivitis (AHC) in a boarding middle school in Guangdong Province, in order to provide a scientific evidence for effective prevention and control of campus AHC outbreaks. Methods: From September 1st to 28th 2023, case identification was conducted among 559 students and 60 faculty members using standardized definition. Descriptive analysis was conducted on the three distrubution patterns of the outbreak. Questionnaires were designed, and a case-control study was adopted to analyze the possible risk factors of the disease transmission. The propensity score matching (PSM) method was used to control the difference of baseline data. Results: A total of 269 cases of AHC were identified, with an attack rate of 43.46%. The pathogen was confirmed as Coxsackie virus A24 variant (CA24v). Among these, 264 cases were students (attack rate of 47.23%) and 5 were staff (attack rate of 8.33%). A total of 153 pairs of PSM were successfully matched. After PSM matching, there were no statistically significant differences in gender, grade and class between the case group and the control group ( χ 2=0.12, 5.41, 11.24, P >0.05). The results of multivariate Logistic regression analysis showed that middle school students whose towels contacted with others ( OR =1.81), and direct contact with other AHC cases recently ( OR =4.89) were more likely to have AHC; while wearing glasses ( OR =0.43) and frequent use of hand sanitizer ( OR = 0.37 ) were less likely to have AHC ( P <0.05). Conclusion The outbreak of AHC is caused by CA24v, demonstrating rapid spread and extensive impact within the school setting.

Objective To investigate and analyze epidemiological characteristics of patients with mycoplasma pneumoniae pneumonia (MPP) from 2020 to 2023, and the risk factors for plastic bronchitis (PB), To provide data support for developing preventive measures. Methods The medical records of 2 257 patients with respiratory tract infection treated at Huai'an Hospital Affiliated to Xuzhou Medical University from 2020 to 2023 were collected. Count the number of MPP patients and analyze the MP detection rate. Multivariate logistic regression analysis and ROC curve was used to screen the risk factors for PB. Results A total of 858 cases were positive for MP antibodies, and the detection rate was 38.02%. There are statistically significant differences in MP detection rates among different genders, age groups, and years (P<0.05). Among the 286 patients diagnosed with MPP and undergoing bronchoscopy, 68 (23.78%) patients had PB. According to univariate and multivariate logistic regression analysis, small age, higher N%, D-D, LDH and AST levels were independent risk factors for PB (P<0.05). ROC curve analysis shows that age and combined detection are the most effective indicators for PB prediction, with areas under the curve of 0.998 and 0.961, respectively. Conclusion MP is the main pathogen of respiratory tract infections in the area from 2020 to 2023. Women and children are more susceptible to MP infection. Small age, high N%, DD, LDH and AST levels are independent risk factors for PB in patients with MPP. Targeted preventive measures should be taken for MP susceptible population, and close attention should be paid to PB related risk factors to prevent disease progression and the occurrence of PB.

Objective To describe and analyze the epidemiological characteristics of scrub typhus in Huai'an, Jiangsu Province from 2006 to 2024 and explore the long-term incidence trend and distribution of high-risk areas, and to formulate targeted prevention and control strategies. Methods The scrub typhus case report data of Huai'an from 2006 to 2024 in the Chinese Disease Prevention and Control Information System were extracted for descriptive analysis. Results A total of 898 cases of scrub typhus were reported in Huai'an, with an average annual incidence rate of 0.96 per 100 000 from 2006 to 2024. There was a turning point in the incidence trend of scrub typhus in 2011. From 2006 to 2011, the annual percentage change (APC) was 47.09% (95% CI: 7.53 - 859.39), and the upward trend was statistically significant (P < 0.05). From 2012 to 2024, the APC was -2.12% (95% CI: -29.09 - 3.75), and the downward trend was not statistically significant. October and November were the high-incidence months, and the total concentration from 2006 to 2024 was 0.93, indicating that scrub typhus had strict seasonality. The circular distribution method estimated that the peak period of the epidemic was from October 11th to November 25th, and the peak day of incidence was November 3rd. Jinhu County was a high-incidence area. The ratio of male to female cases was 1.03. The age group with the highest reported incidence was 40 to < 80 years old. The occupation with the highest proportion was farmers, accounting for 78.03%. Conclusion From 2006 to 2024, scrub typhus in Huai'an shows a peak every 3 - 4 years. Middle-aged and elderly farmers are the key population at risk, and Jinhu County is a key area. In the future, targeted health education should be carried out to effectively control the prevalence of scrub typhus.

OBJECTIVES: To explore the measures to improve the follow-up rate of preterm infants after discharge, and to evaluate the effectiveness of these measures using quality improvement methodology. METHODS: The follow-up status of preterm infants discharged from March to May 2017 was used as the baseline before quality improvement, and a specific quality improvement goal for the follow-up rate was proposed. The Pareto chart was used to analyze the causes of follow-up failure, and a key driver diagram was constructed based on the links involved in improving follow-up rate. The causes of failure were analyzed to determine the key links and intervention measures for quality improvement, and the follow-up rate was monitored weekly using a control chart until the quality improvement goal was achieved. RESULTS: The follow-up rate of preterm infants after discharge was 57.92% (117/202) at baseline before quality improvement, and the quality improvement goal was set to increase the follow-up rate of preterm infants from baseline to more than 80% within 12 months. The Pareto chart analysis showed that the main causes of follow-up failure were deficiencies in follow-up file management and irregular follow-up times (33.70%, 31/92), insufficient follow-up education and poor communication (25.00%, 23/92), and the inability to meet the diverse needs of parents (18.48%, 17/92). Based on the key links for quality improvement and the main causes of follow-up failure, the following intervention measures were adopted: (1) strengthen follow-up publicity and education; (2) build a follow-up team; and (3) establish a follow-up platform and system. The control chart indicated that with the implementation of the above intervention measures, the weekly follow-up rate increased to 74.09% (306/413) in July 2017 and 83.09% (511/615) in December 2017, finally achieving the quality improvement goal. During the COVID-19 pandemic, the follow-up rate of preterm infants fluctuated between 23.54% (460/1 954) and 70.97% (1 931/2 721), and subsequently, it returned to pre-pandemic levels starting in February 2023. CONCLUSIONS The application of quality improvement methodology can help to formulate intervention measures based on the main causes of follow-up failure, thereby improving the follow-up rate of preterm infants after discharge. This quality improvement method is feasible and practical and thus holds promise for clinical application.
Humans ; Quality Improvement ; Infant, Premature ; Infant, Newborn ; Patient Discharge ; Follow-Up Studies ; Female ; Male

OBJECTIVES: To identify potential plasma lipidomic biomarkers that distinguish non-metastatic medulloblastoma (nmMB) from metastatic medulloblastoma (mMB) in children. METHODS: In this prospective study, 17 children with mMB and 20 matched children with nmMB were enrolled. Plasma samples were analyzed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Lipid metabolites were evaluated for their associations and diagnostic performance. RESULTS: Orthogonal partial least squares discriminant analysis based on lipid profiles clearly separated nmMB from mMB, and 14 differential lipids were identified, including DG(18:2/20:4/0:0) and SM(d18:1/20:0). Receiver operating characteristic analysis showed nine metabolites with area under the curve greater than 0.7. Differential lipids were enriched in sphingolipid, glycerophospholipid, and arachidonic acid metabolism, suggesting an association with the metastatic phenotype. CONCLUSIONS Plasma lipidomics provides a new approach to identify mMB, and the identified lipid metabolites may support early diagnosis and treatment, prognostic assessment, and selection of therapeutic targets for metastatic medulloblastoma.
Humans ; Medulloblastoma/diagnosis* ; Lipidomics ; Child ; Male ; Female ; Child, Preschool ; Cerebellar Neoplasms/blood* ; Biomarkers, Tumor/blood* ; Neoplasm Metastasis ; Prospective Studies ; Adolescent ; Lipids/blood*

OBJECTIVE: To investigate the effects of histone deacetylase (HDAC) levels on the proliferation and apoptosis of Burkitt lymphoma cells, and the changes in related signaling molecules in the PI3K/AKT/mTOR signaling pathway, so as to explore the pathogenesis of Burkitt lymphoma. METHODS: HDAC levels in Burkitt lymphoma were detected by RT-PCR and Western blot. CA46 and RAJI cells were treated with the HDAC selective inhibitor VPA. CCK8 assay was used to detect the proliferation ability of cells. Western Blot was used to measure the expression of apoptosis-related proteins, PI3K/AKT/mTOR signaling pathway proteins and their phosphorylation levels. RESULTS: The expression levels of classⅠ HDAC in Burkitt lymphoma were higher than those in normal cells, and the HDAC1 inhibitor VPA could inhibit the proliferation of CA46 and RAJI cells. VPA decreased HDAC expression in CA46 and RAJI cells, inhibited the phosphorylation of PI3K/AKT/mTOR pathway molecules AKT and p70S6K, increased the expression of apoptotic proteins Cleaved Caspase-3, Cleaved Caspase-8, Cleaved Caspase-9 and Bax, and decreased the expression of anti-apoptotic proteins Bcl-2 and PARP. CONCLUSION Inhibition of HDAC activity can Attenuate the proliferation of Burkitt lymphoma cells and induce apoptosis by inhibiting the PI3K/AKT/mTOR signaling pathway activity.
Humans ; Burkitt Lymphoma/pathology* ; Apoptosis ; Cell Proliferation ; Signal Transduction ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Cell Line, Tumor ; Histone Deacetylases/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Histone Deacetylase Inhibitors/pharmacology* ; Phosphorylation

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.

Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.