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.

Objective To investigate the seroprevalence of antibody against Toxoplasma gondii among patients with hematological malignancies, and compare it with that among health individuals, so as to provide insights into unraveling the pathogenesis of hematological malignancies. Methods A total of 225 patients with hematological malignancies in Department of Hematology, Xuzhou Central Hospital and 300 healthy individuals in the same hospital were enrolled from 2017 to 2024. Blood samples were collected from all subjects, and the serum IgG and IgM antibodies against T. gondii were detected using chemiluminescent immunoassay. Demographic and clinical features were collected from patients with hematological malignancies, including gender, age, contact with cats, consumption of raw or undercooked meat, type of malignancy, clinical symptoms, blood transfusion and treatment, and the seroprevalence of anti-T. gondii antibody was compared among patients with different characteristics. Results The age (t = 0.72, P > 0.05) and gender (χ² = 0.93, P > 0.05) were compared between patients with hematological malignancies and healthy individuals. The seroprevalence of T. gondii infection was 20.89% among patients with hematological malignancies and 4.33% among healthy individuals (χ² = 34.81, P < 0.01), and the seroprevalence of anti-T. gondii IgG antibody was 20.89% among patients with hematological malignancies and 4.33% among healthy individuals (χ² = 34.81, P < 0.01), while there was no significant difference in the seroprevalence of anti-T. gondii IgM antibody between patients with hematological malignancies and healthy individuals (1.33% vs. 0; corrected χ² = 2.02, P > 0.05). The seroprevalence of T. gondii infection was 23.08% among patients with leukemia, 16.67% among patients with lymphoma, 19.23% among patients with multiple myeloma, 24.00% among patients with myeloproliferative neoplasm, and 26.09% among patients with myelodysplastic syndrome (χ² = 1.44, P > 0.05), and was all higher than among healthy individuals (corrected χ² = 23.92, 10.74, 13.76, 12.84 and 14.54; all P values < 0.01). In addition, there were no significant differences in the detection of anti-T. gondii antibody among patients with hematological malignancies in terms of gender, age, contact with cats, consumption of raw or undercooked meat, chemotherapy or blood transfusion (χ² = 0.76, 1.97, 0, 2.81, 2.38 and 0.66; all P values > 0.05). Conclusions There is a high risk of T. gondii infection among patients with hematological malignancies, and intensified surveillance of T. gondii infection is recommended among patients with hematological malignancies.

Abstract On October 13 2023, the Beijing Economic and Technological Development Area Center for Disease Control and Prevention recAAAAAeived a report from a school indicating an outbreak of fever among students in Class 2, Grade 4. An on-site epidemiological investigation was immediately conducted. A total of 14 cases were reported, all of whom were students, with an attack rate of 34.15%. The onset of illness was concentrated between October 6 and 15, with the main clinical symptoms being fever, cough and fatigue. There were no cases of hospitalization, severe illness or death. Seven cases tested positive for Mycoplasma pneumoniae P1-Ⅱ. Based on the on-site investigation and laboratory test results, it was an outbreak of influenza-like illness caused by Mycoplasma pneumoniae infection. The likely cause of the spread was cases infecting other classmates through respiratory droplets while attending class. The outbreak occurred only in one class and did not spread to neighboring classes. Schools should actively carry out health education to raise awareness among parents for reporting infectious diseases, and strengthen morning and afternoon screenings to improve the sensitivity of identification.

OBJECTIVE To study the pharmacokinetics of Esketamine hydrochloride nasal spray in rats and ciliary toxicity to maxillary mucosa of bullfrog. METHODS The plasma concentration of esketamine hydrochloride in rats was determined by LC-MS/ MS after intravenous injection of esketamine hydrochloride solution and nasal administration of esketamine hydrochloride； the pharmacokinetic parameters were calculated by using Phoenix WinNonlin 8.1.0 software. Using the maxillary mucosa of isolated bullfrog as a model， the morphological changes of maxillary mucosa were investigated， and the duration and recovery of ciliary oscillation were recorded after nasal administration of esketamine hydrochloride. RESULTS The peak of blood concentration occurred 2 min after nasal administration of esketamine hydrochloride； cmax was （814.58±418.80） ng/mL， AUC0－∞ was （203.75± 92.76） ng·h/mL， and the absolute bioavailability was 60.68%. After nasal administration of esketamine hydrochloride， it was observed that the cilia of bullfrog were arranged neatly， the edges were clear， the cilia tissue structure was complete and the cilia moved actively. The cilia movement time was （178.17±13.30） min for the first time， and after the cilia moved again， the ciliary movement time measured again was （24.50±9.19）min with a relative movement percentage of 53.56%. CONCLUSIONS Esketamine hydrochloride nasal spray has a rapid onset of action， high bioavailability， and low ciliary toxicity.

Objective:To investigate the value of fibrinogen to albumin ratio (FAR), creatinine to albumin ratio (CAR) and platelet to lymphocyte ratio (PLR) in predicting the poor prognosis of hyperlipidemic acute pancreatitis (HLAP).Methods:Clinical data of HLAP patients admitted to the hospital from January 2021 to January and December 2023 were retrospectively collected. According to the prognosis, the patients were divided into two groups: good prognosis group and poor prognosis group.The independent risk factors of HLAP in different prognostic groups were obtained by multivariate Logistic regression analysis. Receiver operating characteristic (ROC) curves were plotted to evaluate the prognostic value of FAR, CAR and PLR alone and in combination.Results:A total of 118 patients with HLAP were included, including 69 patients with good prognosis and 49 patients with poor prognosis.The difference of heart rate, lymphocyte, triglyceride, albumin, creatinine, urea nitrogen, blood calcium, blood glucose, C-reactive protein, procalcitonin, fibrinogen, FAR, CAR, PLR, Bedside indicator of acute pancreatitis Severity score, Acute Physiology and Chronic Health status score, hospitalization time assessment between the two groups was statistically significant ( P<0.05). Multivariate Logistic regression analysis showed that FAR (odds ratio ( OR) = 25.949, 95% confidence interval (95% CI):3.190 ~ 211.080, P = 0.002), CAR ( OR = 1.453, 95% CI:1.095 ~ 1.928, P = 0.010) and PLR ( OR = 1.005, 95% CI: 1.001 ~ 1.009, P = 0.020) were independent risk factors for poor prognosis in HLAP patients. ROC curve analysis showed that the area under the ROC curve (AUC) of FAR, CAR and PLR to predict poor prognosis of HLAP patients were 0.823, 0.781 and 0.652, respectively.The AUC of FAR combined with CAR, FAR combined with PLR and CAR combined with PLR were 0.840, 0.845 and 0.849, respectively.The combined ability of FAR, CAR and PLR to predict poor prognosis in HLAP patients was (AUC=0.875,95% CI:0.814 ~ 0.937). When the cut-off value was 0.387, the sensitivity was 83.7%, and the specificity was 79.7%. Conclusions:The prognostic value of FAR, CAR and PLR in HLAP patients is better than that of single or pairwise combination.

Objective To evaluate the differences in chemical composition and pharmacological effects between Angelica-Astragalus medicine pair decoction(DGD)and traditional decotion,and to provide a reference for the rational clinical application of Danggui Buxue decoction.Methods With the two comparison methods of unified and non-uniform raw material source batches,we set up different sample groups,established characteristic maps by HPLC,and evaluated the chemical components based on the similarity of characteristic maps,component types,index component content,common peak area,and other factors.The efficacy of the drug was evaluated in the hemorrhagic blood deficiency model mice.Results ①The similarity of the feature map between the DGD and TD was high(similarity was greater than 0.87).②The number of chromatographic peaks was inconsistent.Traditional decoction from self-purchased decoction pieces,or traditional decoction-Factory A decoction pieces had a total of 12 chromatographic peaks each.The DGD of Factory A had a total of 15 chromatographic peaks.There were 10 chromatographic peaks in the DGD of Factory B.③The contents of ferulic acid and calycosin 7-O-glucoside(CG)in DGD of Factory A were higher than those in traditional decoction(P<0.05,n=3).There was no significant difference between DGD and TD ferulic acid content in Factory B,but the content of CG was lower than that in traditional decoction(P<0.05).④The total area of common peaks in DGD was different from that in TD.The relative total ratios of the contents of the components in the self-purchased traditional decoction pieces,the traditional decoction pieces of Factory A,the formula granules of Factory A,and the formula granules of Factory B were 1.00,0.96,2.14,0.60,respectively.⑤Both DGD and traditional decoction could significantly promote the recovery of hemoglobin and red blood cells in hemorrhagic anemia model mice(P<0.01);Compared with the model control group,there was a significantly difference(P<0.05)except for the DGD group of Plant B.There was no significant difference between DGD and TD of Plant A,but there was a very significant difference between DGD and TD of Plant B(P<0.01).Conclusion Whether the raw material source batch is consistent or not,DGD and TD have certain differences in chemical composition.In terms of pharmacological effect,DGD,prepared from a unified batch of decoction pieces,has similar efficacy to traditional decoction in alleviating hemorrhagic anemia.There are certain differences in the pharmacological effects between DGD prepared from different batches of decoction pieces and traditional decoctions.The differences caused by the different preparation processes of the same source batch of prepared slices were compared,and the quality differences of the formula granules from different manufacturers were caused by the different source batches of prepared slices and different preparation processes,indicating the necessity and urgency of the country to formulate a unified quality standard for formula granules and related process specifications.

Objective:To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on the childhood Epstein-Barr virus(EBV)-positive lymphoproliferative diseases(EBV + LPD). Methods:The clinical features, treatment course, and prognosis of 9 children with EBV + LPD who underwent allo-HSCT in Children′s Hospital Affiliated to Zhengzhou University from July 2019 to July 2022 were analyzed retrospectively. Results:All the 9 children underwent histopathological examination, including 6 patients with EBV-positive T-cell lymphoproliferative disease (EBV + T-LPD), 1 with pulmonary lymphomatoid granuloma, and 2 with systemic EBV-positive T-cell lymphoma.There were 6 males and 3 females, with the median age of 5.8 (1.5-13.0) years.At the initial diagnosis, plasma and peripheral EBV-DNA copy at the initial diagnosis was (5.67-865.00)×10 2/mL, and (5.13-1 250.00)×10 2/mL, respectively.The EBV-DNA load of cerebrospinal fluid increased to (5.18-291.00)×10 2/mL in 3 cases.The whole exon sequencing data showed no abnormality in 3 cases, pulmonary lymphomatoid granuloma with the IL2RG mutation in 1 case and EBV + T-LPD with a hemizygous mutation in the SH2D1A gene as the pathogenic mutation in 1 case.Pathogenic mutations were not detected in the remaining 4 cases.The course of disease before transplantation was 5.4(3.0-10.0) months.Disease status before transplantation was as follows: all 3 cases of lymphomas had partial regression; 2 cases of EBV + T-LPD had active disease; and 4 cases had no active disease.Among the donors, there were 5 cases of half-matched relatives, 2 cases of full-matched siblings and 2 cases of unrelated full-matched donors.The median number of mononuclear cells in peripheral blood and/or bone marrow hematopoietic stem cell was 6.60(3.64-12.18)×10 8/kg, while the median implantation time of neutrophils was 18(9-23) days.One month after the transfusion of hematopoietic stem cells, plasma EBV-DNA copy was negative in all cases, and peripheral EBV-DNA copy was negative in 7 cases.The copy number in the other 2 cases was 10 2/mL.At the 3-month evaluation, plasma and peripheral EBV-DNA copy were negative in all cases.In addition, 3 cases of lymphomas achieved radiographic complete remission, and 6 cases of EBV + T-LPD were inactive.All transplant-related complications were effectively controlled after medication.Following the median follow-up of 24 (11-42) months, all patients had disease-free survival.Serious impact on the quality of life due to graft versus host disease was not reported. Conclusions:allo-HSCT is an effective treatment of childhood EBV + LPD, which is able to control transplant-related complications.Children with EBV + LPD can achieve long-term disease-free survival through transplantation.

Objective:To analyze the prognostic risk factors of patients with traumatic pancreatitis (TP) and establish an early combined prediction of multiple indicators model for TP.Methods:Patients admitted to the ICU of the First Affiliated Hospital of Zhengzhou University from June 2017 to June 2022 were collected retrospectively. Based on their prognosis, the patients were divided into two groups: the good prognosis group and the poor prognosis group. The general data such as sex, age, underlying diseases, Glasgow Coma Scale (GCS), acute physiology and chronic health evaluationⅡ (APACHEⅡ), injury severity score (ISS), bedside index for severity in acute pancreatitis (BISAP), and clinical test indices such as blood routine, blood coagulation, blood gas analysis, and liver and kidney function at admission were compared between the two groups. Univariate analysis and multivariate logistic regression analysis were used to screen the early independent predictors of poor prognosis of TP, and the prediction model of TP was established by combining all of the independent indicators. The receiver operating characteristic (ROC) curve of each independent predictor and prediction model was drawn, and the area under the curve (AUC), sensitivity, specificity, and optimal cut-off value were calculated to examine the diagnostic impact of each independent predictor and the combined prediction model.Results:There were statistically significant differences in the complication rate of mental disorders, GCS, APACHE II, combined craniocerebral injury, combined chest injury, activated partial thromboplastin time, fibrin(pro)degradation products, lactate, aspartate aminotransferase, glomerular filtration rate, amylase, lipase, NT-proBNP, myoglobin, procalcitonin, ISS, and BISAP between the good and poor prognosis groups (all P<0.05). Multivariate logistic regression analysis showed that lactate ( OR=1.636, 95% CI: 1.046-2.559), lipase ( OR=1.005, 95% CI: 1.001-1.008), and ISS ( OR=1.161, 95% CI: 1.064-1.266) were independent risk factors influencing the prognosis of patients with TP. Based on the risk factors listed above, a prediction model was created: Logit P=-9.260+0.492×lactate+0.005×lipase+0.149×ISS, and the ROC curve was plotted. The AUC curve of the prediction model was 0.96 (95% CI: 0.91-1.00). Conclusions:Lactate, lipase, and ISS are early independent risk factors associated with the prognosis of TP. Their combined multi-indicator prediction model has an excellent clinical prediction effect, which can provide a clinical reference for early prediction and treatment of TP.

Objective:To observe the multimodal imaging features of acute macular neuroretinopathy (AMN) associated with COVID-19.Methods:A retrospective case study. A total of 52 eyes of 26 patients of AMN associated with COVID-19 diagnosed in Handan Eye Hospital from December 8 to 20, 2022 were included in the study. There were 8 males and 18 females, with the mean age of (33.8±8.1) years. All the patients were bilateral. The time from diagnosis of COVID-19 to the onset of vision loss was 3 to 6 days. All patients underwent the examinations of best corrected visual acuity (BCVA), fundus color photography, infrared fundus photography (IR), fundus autofluorescence (AF), and optical coherence tomography (OCT). Fluorescein fundus angiography (FFA) combined with indoxine green angiography (ICGA) were performed in 12 eyes, and visual field were performed in 18 eyes. Multimodal image features of the affected eye were retrospectively analyzed.Results:The BCVA of the affected eye was 0.25 to 1.0. Round or mottled grayish-white lesions in the macular area were seen in all affected eyes. IR examination showed irregular map-like weak reflex in macular region. AF examination showed speckled fluorescence enhancement in lesion related areas in 3 eyes. FFA combined with ICGA showed weak fluorescence in the macular region in 8 eyes. OCT examination showed patchy strong reflection in the outer plexus layer (OPL) and outer nuclear layer (ONL) of macular area in all affected eyes, and partial absence of outer membrane and ellipsoid band. The en-face OCT showed petal-like intense refleciton between OPL and ONL. Eighteen eyes underwent visual field, and 15 eyes had central dark spots.Conclusion:The characteristic manifestations of AMN associated with COVID-19 are speckled or round-like grayish-white lesions in the macular area, weak reflexes in IR, enhanced OPL and ONL reflexes in OCT, and petal-like intense refleciton changes between OPL and ONL can be seen in en-face OCT.

Background Flurochloridone (FLC) is toxic to male reproduction and can induce apoptosis of testicular tissue and supporting cells under oxidative stress. Of particular concern is whether nuclear factor-erythrocyte 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway and nuclear factor kappa B (NFκB) signaling pathway participate this process. Objective To observe apoptosis of testicular tissue and sertoli TM4 cells and alterations of Nrf2/HO-1 and NFκB signaling pathways in mice treated with FLC in vivo/in vitro. Methods (1) Animal experiment. Testis samples were harvested from male C57BL/6 mice after 28-day FLC (0, 3, 15, 75, and 375 mg·kg⁻¹ per day) exposure via oral route. Malondialdehyde (MDA) and superoxide dismutase (SOD) in homogenate of testicular tissue were measured by colorimetry. Apoptosis of testicular tissue was evaluated by TUNEL staining. Expression and distribution of Nrf2 and NFκB were detected by immunohistochemistry. Protein expression levels of Nrf2, HO-1, NAD(P)H: quinone oxidoreductase 1 (NQO1), NFκB, inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ), and phosphorylated recombinant inhibitory subunit of nuclear factor kappa-B alpha (P-IκBα) in testicular tissue homogenate were determined by Western blotting. (2) Cell experiment. TM4 cell lines were treated with 40, 80, 120, 160, and 200 μmol·L⁻¹ FLC for 6 h, and cell viability was detected by CCK-8. After 6 h exposure to 40, 80, and 160 μmol·L⁻¹ FLC, the apoptosis rate was detected by flow cytometry, and the protein expression levels of Nrf2, HO-1, NQO1, NFκB, IKKβ, and IκBα were detected by Western blotting. Results (1) Animal experiment. Apoptosis occurred in the interstitial and basal parts of spermatogenic tubules in male C57BL/6 mice after 28 days of oral FLC exposure. Compared with the control group, the MDA level in testicular tissue of the 375 mg·kg⁻¹ FLC-treated group was significantly increased (P<0.05), and the SOD activity was significantly decreased (P<0.05). After 375 mg·kg⁻¹ FLC exposure, apoptosis occurred in the interstitial and basal parts of spermatogenic tubules. The results of immunohistochemistry showed the expression of Nrf2 and NFκB in the interstitium and basal part of spermatogenic tubules of the treated groups. Compared with the control group, the protein levels of Nrf2, NQO1, P-IκBα, NFκB, and IKKβ in the 15, 75, and 375 mg·kg^-1 groups were significantly increased (P<0.001), and the HO-1 protein level was significantly increased in the 375 mg·kg⁻¹ group (P<0.001). (2) Cell experiment. Compared with the control group, the TM4 cell viabilities in the 40, 80, 120, 160, and 200 μmol·L⁻¹ FLC-treated groups significantly decreased (P<0.01). The apoptosis rates were significantly increased (P<0.05), and the apoptosis rates increased from 5.7% in the control group to 7.4%, 9.4%, and 11.7% in the 40, 80, and 160 μmol·L⁻¹, respectively. The Nrf2 protein level in the 40 μmol·L⁻¹ group was significantly increased (P<0.01), while the levels significantly decreased in the 80 and 160 μmol·L⁻¹ groups (P<0.01). The HO-1 protein levels in the 40, 80, and 160 μmol·L⁻¹ groups were significantly increased (P<0.01). The level of NQO1 protein in the 40 μmol·L⁻¹ group was significantly increased (P<0.01). The NFκB protein levels were significantly increased in the 80 and 160 μmol·L⁻¹ groups (P<0.001). The IκBα protein levels were significantly decreased in all treated groups (P<0.001). The IKKβ protein had no significant change. Conclusion FLC induces testicular tissue apoptosis, and the process affects Nrf2/HO-1 signaling pathway and NFκB signaling pathway. The in vitro study confirms that FLC could induce apoptosis of TM4 cells and activate Nrf2/HO-1 and NFκB signaling pathways.