Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

ObjectiveTo investigate the effects of paeoniflorin （PF） on neuroinflammation and cognitive impairment in the rat model of Alzheimer's disease （AD） and to clarify whether its mechanism is associated with regulation of the Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） signaling pathway. MethodsGlycosides related to AD-associated neuroinflammation were screened through bibliometric analysis， and the potential targets of PF were predicted through network pharmacology and molecular docking. A rat model of AD was established by intraperitoneal injection of D-galactose （100 mg·kg^-1·d^-1）. Rats were assigned into a control group， a model group， a PF （200 mg·kg^-1） group， and a donepezil （0.5 mg·kg^-1·d^-1） group， and drugs were administered by gavage for 21 days. The learning and memory abilities were evaluated by the Morris water maze （MWM）. Hematoxylin-eosin （HE） staining and Nissl staining were performed to observe hippocampal neuronal morphology. The mRNA levels of inflammatory factors were determined by Real-time quantitative polymerase chain reaction （Real-time PCR）， and the protein levels of molecules in the JAK2/STAT3 signaling pathway were determined by Western blot. ResultsCompared with the control group， the model group showed prolonged escape latency and decreased platform crossings and time spent in the target quadrant （P<0.05， P<0.01）， accompanied by increased expression of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α）， as well as elevated ratios of phosphorylated （p）-JAK2/JAK2 and p-STAT3/STAT3 （P<0.01）. Compared with the model group， the PF group and donepezil group exhibited shortened escape latency and increased platform crossings and time spent in the target quadrant （P<0.05， P<0.01）， decreased expression levels of IL-1β and TNF-α， upregulated mRNA levels of interleukin-4 （IL-4） and interleukin-10 （IL-10）， and reduced ratios of p-JAK2/JAK2 and p-STAT3/STAT3 （P<0.05， P<0.01）. ConclusionPaeoniflorin can alleviate cognitive impairment and neuroinflammation in the rat model of AD by inhibiting the JAK2/STAT3 signaling pathway.

Objective The aim of the study is to analyze the incidence patterns and epidemiological characteristics of parasitic and vector-borne diseases in the Minhang and Jinshan districts of Shanghai, and provide evidence-based information for optimizing prevention and control measures. Methods We collected information from epidemic reports and epidemiological investigation forms for cases of parasitic and vector-borne diseases from 2005 to 2024 in Shanghai's Minhang and Jinshan districts. Descriptive epidemiological method were adopted to conduct a comparative analysis of incidence trends, epidemic characteristics, and infection sources. Results A total of 229 cases in 7 categories were reported between 2005 and 2024, with an average annual incidence rate of 0.36/100 000. The average annual incidence rate in Minhang District was significantly higher than that in Jinshan District. The most prevalent diseases were malaria and dengue fever, followed by Japanese encephalitis. Monthly case reports were available, predominantly from June to October, with a peak in July-August. A statistically significant difference was observed between the two districts in case distribution during June-October (P＜0.001), whereas no significant difference was found for July-August (P=0.331). The majority of cases were young men (111/229,48.47%), aged 20-39 years. Migrant workers/farmers constituted the largest occupational group (55/229, 24.02%). Registered residents of other provinces and cities (147/229,64.19%), and the main source of infection was overseas importation (112/229,48.91%). There were no statistically significant differences in gender and household-registration composition between the two districts (P＞0.05). Significant differences existed in age, occupation, and source of infection (P＜0.05). The imported diseases were malaria and dengue fever, with Africa and Southeast Asia being the primary source locations. Malaria was the predominant disease imported from other provinces and cities, with cases having been imported from abroad since 2012. Local infections were mainly Japanese encephalitis, followed by malaria (with the last local case reported in 2010). Cases between 2005 and 2009 were predominantly imported from other provinces and cities. The proportion of cases imported from abroad increased sharply after 2010, particularly in Minhang District. Local infections sometimes arise in Jinshan District, with Japanese encephalitis serving as the primary type. Conclusions Incidence rates of parasitic and vector-borne diseases in Minhang and Jinshan districts have generally remained low. To further reduce this disease burden, it will be necessary to strengthen joint measures for prevention and control, eliminate the environmental risk factors of vector organisms, enhance monitoring and precise control of the environment and inbound personnel to prevent the occurrence and transmission of parasitic and vector-borne diseases.

Objective To explore the intervention effect of acceptance and commitment therapy(ACT)on adolescent depression patients with non-suicidal self-injury.Methods A total of 60 adolescent depression patients with non-suicidal self-injury treated in Guilin Mental Health Center from June 2022 to June 2023 were selected as study objects,and they were divided into observation group and control group according to random number table method,with 30 cases in each group.Patients in control group received routine nursing,and patients in observation group received ACT intervention at the same time of routine nursing.Both groups received intervention for 6 weeks.The scores of self-rating depression scale(SDS),self-rating anxiety scale(SAS),nurses's global assessment of suicide risk(NGASR),acceptance and action questionnaire-Ⅱ(AAQ-Ⅱ)and cognitive fusion questionnaire(CFQ)before and after treatment were compared between two groups.Results After the intervention,the scores of SDS,SAS,NGASR,AAQ-Ⅱ and CFQ in observation group were significantly lower than before the intervention(P＜0.05).The NGASR score of observation group was significantly lower than that of control group(P＜0.05).There were no significant differences in SDS,SAS,AAQ-Ⅱ and CFQ scores between two groups(P＞0.05).Conclusion ACT can effectively improve the non-suicidal self-injury behavior of patients,help patients improve psychological flexibility,and is conducive to depression treatment.

Objective To analyze the incidence,colonization pathways,and predictive factors of bacterial colonization of epidural analgesia catheters in patients with chronic pain.Methods A total of 150 patients with chronic pain who underwent continuous epidural catheterization(catheter in-dwelling time of 7 to 10 days)were selected as study subjects.Samples from three sites were collect-ed for bacterial culture.Clinical data of the patients were collected,and the positive rate of bacterial culture,characteristics of bacterial species distribution,and bacterial colonization pathways were ana-lyzed.The efficacy of predictive factors was assessed using the receiver operating characteristic(ROC)curve.Results The positive rates of bacterial culture in samples from the skin swabbing fluid around the puncture site,the subcutaneous segment of the catheter,and the catheter tip were 22.0％,7.3％,and 8.7％,respectively.Staphylococcus epidermidis was the predominant colonizing bacterial species.Spearman correlation coefficient analysis showed a significant correlation between the results of bacterial culture from the skin around the puncture site and catheter tip colonization(r=0.47,P＜0.01).ROC curve analysis revealed that the area under the curve of bacterial culture results from the skin around the puncture site in predicting catheter tip bacterial colonization was 0.843,with a sensitivity of 84.9％and a specificity of 84.6％.Conclusion Bacterial migra-tion along the catheter is the main pathway for catheter tip bacterial colonization,and the results of bacterial culture from the skin around the puncture site are an effective predictive factor for the risk of bacterial colonization.

Objective:To study the clinical and pathological features, immunophenotypes, molecular genetics characteristics, differential diagnosis, and prognostic factors of pulmonary and tracheal glomus tumors.Method:Eight cases of pulmonary and tracheal glomus tumors were collected in Jiangsu Provincial Hospital (including 1 consultation, from Gaochun People's Hospital, Nanjing, China) between May 2015 and April 2023, and their clinical and imaging data, pathological morphology, and immunohistochemical characteristics were retrospectively analyzed. Gene testing and follow-up were performed.Result:There were 5 males and 3 females with onset ages ranging from 29 to 75 years old, median age 63.5 years. Among the patients, 5 cases were located in the trachea and 3 cases in the lungs. Under light microscopy, 5 cases were benign glomus tumors with clear boundaries, diffuse sheet or nest-like distribution, small, round or short spindle-shaped tumor cells, rounded and centered nuclei, and no obvious nuclear mitosis was seen. Two cases of glomus tumor of uncertain malignant potential showed an infiltrative growth pattern involving smooth muscle, nerves and blood vessels with necrosis and calcification, the tumor cells were more uniform in size, round or short spindle-shaped nuclei, and no obvious nuclear mitosis was seen; One case of malignant glomus tumor was seen in sarcomatous areas, lung membrane invasion and necrosis, the tumor cells were highly heterogeneous, binucleated and multinucleated, with nuclear mitoses of 20/50 high power field (HPF), and pathologic nuclear mitoses were easy to be seen. Immunohistochemically, SMA, Calponin, H-caldesmon, Vimentin and Collagen Ⅳ were all positive (8/8). Some cases expressed Syn (3/8) and Bcl-2 (4/8). The Ki-67 proliferation index was 1-2% (7/8) and 40% (1/8). BRAF V600E were detected as wild-type (8/8), and no mutations were detected in exons 2, 3, and 4 of KRAS human EML4- ALK fusion gene were negative in 5 surgical cases. Case 6 showed HMBOX1- ALK gene fusion, TERT gene mutation and CDKN2A gene deletion, and case 8 showed CARMN- NOTCH2 gene fusion. Seven cases were followed up (8-103 months, median follow-up time 30 months), 1 case was lost, 1 case recurred 21 months after surgery, and others with no evidence of recurrence or metastasis. Conclusions:Pulmonary and tracheal glomus tumors are very rare and need to be differentiated from other common tumors by combining pathological morphology and immunohistochemistry. Maybe there are some differences in the malignant diagnostic criteria and molecular genetic characteristics between visceral derived glomus tumors and soft tissue derived tumors of the same kind, such as limbs and skin. More data accumulation is needed.

Objective To observe the clinical efficacy and safety of vericiguat tablets combined with sacubitril valsartan sodium(Sac/Val)tablets in the treatment of patients with heart failure with reduced ejection fraction(HFrEF).Methods The HFrEF patients were divided into control group and treatment group according to the cohort method.The control group was treated with Sac/Val tablets 200 mg per time,bid,orally.On the basis of control group,the treatment group was treated with vericiguat tablets 2.5 mg per time,qd,taken with meal.Two groups were treated for 3 months.The clinical efficacy,left ventricular ejection fraction(LVEF),left ventricular end-diastolic dimension(LVEDD)and end-systolic diameter(LVESD),levels of high sensitivity C-reactive protein(hs-CRP),interleukin-6(IL-6),nitric oxide(NO),N-terminal pro-brain natriuretic peptide(NT-proBNP),blood urea nitrogen(BUN)and serum creatinine(SCr),and safety were compared between the two groups.During follow-up,the heart failure rehospitalization rates and major adverse cardiovascular events were compared between the two groups.Results Treatment group was enrolled 53 patients,control group was enrolled 53 patients.After treatment,the total effective rates of treatment and control groups were 94.34％(50 cases/53 cases)and 81.13％(43 cases/53 cases)with statistical significant difference(P＜0.05).After treatment,the LVEF of treatment and control groups were(48.02±5.20)％and(43.02±4.33)％,the LVEDDs were(52.85±6.30)and(55.63±6.88)mm,the LVESDs were(41.64±6.40)and(44.22±5.85)mm,the levels of hs-CRP were(10.22±2.63)and(14.60±2.98)mg L-1,the levels of IL-6 were(14.48±2.40)and(17.36±2.52)pg·mL-1,the levels of NO were(102.60±20.16)and(92.16±16.33)μmol·L-1,the levels of NT-proBNP were(898.74±102.20)and(1315.60±182.64)ng·L-1,the levels of BUN were(12.02±2.28)and(13.45±2.33)mmol·L-1,the levels of SCr were(82.22±5.89)and(85.64±6.03)μmol·L-1,the heart failure rehospitalization rates were 5.66％and 13.21％,respectively;the differences were statistical significant between two groups(all P＜0.05).The adverse drug reactions of treatment group were hyperkalemia,hypotension,renal dysfunction,dizziness and headache,while those in control group were renal dysfunction,hyperkalemia,and hypotension.The major adverse cardiovascular events of treatment group were angina pectoris and acute myocardial infarction,while those in control group were angina pectoris,acute myocardial infarction and atrial fibrillation.The incidences of total adverse drug reactions in treatment and control groups were 13.21％and 7.55％,the incidences of major adverse cardiovascular events were 5.66％and 13.21％,respectively,without statistically significant differences(all P＞0.05).Conclusion Vericiguat tablets combined with Sac/Val tablets have a definitive clinical efficacy in the treatment of HFrEF patients,which can improve cardiac and endothelial function,reduce inflammatory response and readmission times,without increasing the incidences of adverse drug reactions.

Objective To observe the efficacy of self-made auxiliary reduction device combined with sinus tarsi approach(STA)in the treatment of Sanders type Ⅱ to Ⅳ calcaneal fractures.Methods A total of 40 patients with Sanders type Ⅱ to Ⅳ calcaneal fractures admitted to our hospital from January to June 2023 were selected and divided into the control group and the observation group by the random number table method,with 20 cases in each group.Patients in the control group underwent surgical treatment with the heel extensile lateral approach(ELA),while patients in the observation group underwent surgical treatment with the auxiliary reduction device combined with STA.The surgical-related indicators,postoperative complications and ankle-foot anatomical indicators of patients in the two groups were compared.The recovery of limb function was evaluated by the American Orthopaedic Foot and Ankle Society(AOFAS)ankle-hindfoot scale and Maryland foot function score.Results There was no statistically significant difference in the operation time,postoperative incision drying time,or duration of postoperative pain between the two groups(P>0.05).The postoperative suture removal time of the patients in the observation group was shorter than that of the control group,and the difference was statistically significant(P<0.05).The incidence of skin edge necrosis of incision and the total incidence of complications of patients in the observation group were significantly lower than those in the control group(P<0.05).The B?hler angle and Gissane angle of patients in both groups increased after surgery compared with those before surgery(P<0.05);there was no statistically significant difference in the B?hler angle or Gissane angle after surgery of patients between the two groups(P>0.05).The AOFAS score1 week after surgery of the patients in the observation group was higher than that in the control group(P<0.05),while there were no statistically significant differences in the AOFAS scores or Maryland scores of patients at other time points between the two groups(P>0.05).Conclusion The use of the auxiliary reduction device in surgical treatment with STA for Sanders type Ⅱ to Ⅳ calcaneal fractures can effectively restore the function of the foot and ankle,with short postoperative suture removal time and low incidence of postoperative complications.

The complement component 4 binding protein alpha(C4BPA)gene is the alpha chain of complement binding protein 4.As a plasma protein involved in the complement and coagulation systems,it can influence immune responses and lipid metabolism.In order to study the polymor-phism of C4BPA gene and its correlation with milk quality traits in Chinese Holstein cows,genom-ic DNA was extracted from blood samples of 92 Chinese Holstein cows,and the target fragment of C4BPA gene was amplified by PCR,and the association analysis was performed by using direct se-quencing to obtain the SNP loci and milk quality traits.The results showed that among the four SNPs found at the third intron of the C4BPA gene,I3-11 G＞A was highly significantly correlated with milk protein and urea nitrogen(P＜0.05),I3-291 T＞G was significantly correlated with lac-tose(P＜0.05),I3-374 C＞T was highly significantly correlated with lactose and urea nitrogen(P＜0.05),and I3-375 T＞G was highly significantly correlated with lactose(P＜0.05),milk pro-tein and urea nitrogen.The chi-square test values for each point indicated that the population was in genetic equilibrium.Individuals of haplotype combination H1 H1 had the highest lactose content,and haplotype combination H1H2 can be used as the best haplotype combination in the molecular selection work of dairy cows.

Dysregulated RNA splicing is a well-recognized characteristic of colorectal cancer (CRC); however, its intricacies remain obscure, partly due to challenges in profiling full-length transcript variants at the single-cell level. Here, we employ high-depth long-read scRNA-seq to define the full-length transcriptome of colorectal epithelial cells in 12 CRC patients, revealing extensive isoform diversities and splicing alterations. Cancer cells exhibited increased transcript complexity, with widespread 3'-UTR shortening and reduced intron retention. Distinct splicing regulation patterns were observed between intrinsic-consensus molecular subtypes (iCMS), with iCMS3 displaying even higher splicing factor activities and more pronounced 3'-UTR shortening. Furthermore, we revealed substantial shifts in isoform usage that result in alterations of protein sequences from the same gene with distinct carcinogenic effects during tumorigenesis of CRC. Allele-specific expression analysis revealed dominant mutant allele expression in key oncogenes and tumor suppressors. Moreover, mutated PPIG was linked to widespread splicing dysregulation, and functional validation experiments confirmed its critical role in modulating RNA splicing and tumor-associated processes. Our findings highlight the transcriptomic plasticity in CRC and suggest novel candidate targets for splicing-based therapeutic strategies.
Humans ; Colorectal Neoplasms/metabolism* ; RNA Isoforms/metabolism* ; Single-Cell Analysis ; RNA Splicing ; Gene Expression Regulation, Neoplastic ; RNA, Neoplasm/metabolism* ; Transcriptome