Background: Influenza A virus (IAV) is a negative-sense RNA virus of the Orthomyxoviridae family and is the etiological agent of a highly contagious acute respiratory disease that can lead to acute lung injury. Objective: To elucidate the molecular mechanisms of IAV infection, an integrative research approach combining gene expression profiling, multinetwork analysis, and in vivo experimental validations was employed. Methods: First, a series of network-based analyses were performed, including protein-protein interaction network construction, weighted gene co-expression network analysis, and subsequent gene set enrichment analysis, to identify the major underlying mechanisms of IAV infection. Following gene expression analysis, core targets, both direct and indirect regulators, were screened. An IAV (H1N1) strain A/PR/8/34-induced acute lung injury mouse model was constructed for in vivo validations. Batch one included two groups to evaluate findings from the multi-network analysis: Mock (n = 10; 5 males and 5 females) and IAV (n = 10; 5 males and 5 females). Batch two included three groups to assess the role of toll-like receptor 3 (TLR3) in IAV infection: Mock (n = 6; 3 males and 3 females), IAV (n = 6; 3 males and 3 females), and TLR3 inhibitor (n = 6; 3 males and 3 females). Body weight was measured on days 0, 3, and 5 after infection. On day 5, lung tissues were collected to assess viral load and histopathological changes. Key targets were examined using enzyme-linked immunosorbent assay, Western blotting, and immunofluorescence staining, both in sera and lung tissues. Results: IAV infection was significantly associated with dysregulation of the immune-inflammation system, such as the LTR, nucle-otide-binding oligomerization domain-(NOD) like receptor, retinoic acid-inducible gene I-like receptor, and nuclear factor kappa-B signaling pathways. Gene set enrichment analysis further indicated that the TLR and necroptosis signaling pathways played crucial roles in the progression of IAV infection (TLR signaling pathway normalized enrichment score = 2.3941, P = 1.00 × 10 ⁻¹⁰; necroptosis normalized enrichment score = 1.9421, P = 6.21 × 10 ⁻⁷). Among the core targets, TLR3 and mixed lineage kinase domain-like protein (MLKL) may regulate gene expression at the transcriptional level (all P < 0.05). In vivo validation using an IAV (PR8) infected acute lung injury mouse model demonstrated increased viral load and lung index, alveolar structural damage, and inflammatory cell infiltration. Immunofluorescence staining exhibited large gaps in Lamin B1 staining and breaches in Emerin signals following IAV-PR8 infection. Expression levels of TLR3, p-receptor-interacting serine/threonine-protein kinase 3 (RIPK3)/RIPK3, and p-mixed lineage kinase domain-like protein (MLKL)/MLKL proteins in lung tissues, as well as proinflammatory factors and mediators in sera, were significantly elevated after IAV infection. Moreover, enhanced neutrophil infiltration (myeloperoxidase) and citrullinated histone H3 (a neutrophil extracellular trap-specific marker), both established indicators of neutrophil extracellular trap formation, were observed. Notably, treatment with a TLR3 inhibitor significantly ameliorated IAV-induced acute lung injury by regulating necroptosis-related targets. Conclusion: Our study provides network-based in vivo evidence that TLR3-receptor-interacting serine/threonine-protein kinase 3-MLKL-mediated necroptosis may underlie IAV-induced acute lung injury and could serve as a potential therapeutic target in severe influenza cases.

A bladder cancer patient underwent intravesical Bacillus Calmette-Guérin (BCG) instillation in Xiamen Branch, Zhongshan Hospital, Fudan University in April 2023. Following 8 instillations the patient presented with fever, cough and dyspnea, and was diagnosed as interstitial pneumonia (IP). Symptoms resolved after anti-tuberculosis and methylprednisolone treatment, with subsequent successful discharge. Using the keywords ′Bacillus Calmette-Guérin, ′ ′intravesical instillation, ′ ′pneumonia, ′ Wanfang Data, China National Knowledge Infrastructure(CNKI), Weipu(VIP), and PubMed databases were searched for relevant literature published between January 2014 and June 2024, and 20 cases of BCG instillation-induced pneumonia were retrieved, including 10 IP cases and 10 miliary pneumonia cases. Among 10 IP cases, 7 received corticosteroids combined with anti-tuberculosis therapy. Two cases unresponsive to combination therapy resulted in mortality, while others showed therapeutic efficacy. Miliary pneumonia demonstrated better prognosis, with 6 cases achieving complete remission through anti-tuberculosis monotherapy. The results indicate that severe BCG-related pneumonia generally necessitates combined anti-tuberculosis and corticosteroid therapy.

A bladder cancer patient underwent intravesical Bacillus Calmette-Guérin (BCG) instillation in Xiamen Branch, Zhongshan Hospital, Fudan University in April 2023. Following 8 instillations the patient presented with fever, cough and dyspnea, and was diagnosed as interstitial pneumonia (IP). Symptoms resolved after anti-tuberculosis and methylprednisolone treatment, with subsequent successful discharge. Using the keywords ′Bacillus Calmette-Guérin, ′ ′intravesical instillation, ′ ′pneumonia, ′ Wanfang Data, China National Knowledge Infrastructure(CNKI), Weipu(VIP), and PubMed databases were searched for relevant literature published between January 2014 and June 2024, and 20 cases of BCG instillation-induced pneumonia were retrieved, including 10 IP cases and 10 miliary pneumonia cases. Among 10 IP cases, 7 received corticosteroids combined with anti-tuberculosis therapy. Two cases unresponsive to combination therapy resulted in mortality, while others showed therapeutic efficacy. Miliary pneumonia demonstrated better prognosis, with 6 cases achieving complete remission through anti-tuberculosis monotherapy. The results indicate that severe BCG-related pneumonia generally necessitates combined anti-tuberculosis and corticosteroid therapy.

Objective:To explore the characteristics of renal oxidative stress injuries in rats with high-voltage electric burns and the intervention effects of breviscapine.Methods:This study was an experimental study. One hundred and sixty 8-10-week-old male Sprague Dawley rats were divided into sham injury group, electric burn group, saline group, low breviscapine group, middle breviscapine group, and high breviscapine group, with 60 rats in each of the sham injury group and electric burn group, 10 rats in each of the other 4 groups, respectively. The rats in sham injury group and electric burn group were divided into 10 rats at each time point, including post injury hour (PIH) 0 (immediately), 8, 24, 48, and 72, and post injury week (PIW) 1. The rats in sham injury group were not conducted with electrical current to cause sham injury. The rats in the other 5 groups were caused high-voltage electric burns. The rats in sham injury group and electric burn group were not treated after injury. The rats in saline group, low breviscapine group, middle breviscapine group, and high breviscapine group were intraperitoneally injected with 5 mL/kg normal saline or 0.4, 1.6, and 4.0 g/L breviscapine, repeated every 24 h until PIH 72. After the model was successfully made, 14 rats died, including 1, 2, 2, and 1 rat (s) at PIH 24, 48, and 72 and PIW 1 in electric burn group, 4, 1, 2, and 1 rat (s) at PIH 72 in saline group, low breviscapine group, middle breviscapine group, and high breviscapine group, respectively. The kidney tissue collected from rats in the 6 groups was weighed and the kidney/body weight ratio was calculated. The left upper pole tissue of kidney was collected from each 4 rats in sham injury group, and in electric burn group at PIH 8, 24, 48, and 72 and PIW 1, and in saline group, low breviscapine group, middle breviscapine group, and high breviscapine group at PIH 72. The renal tubular and renal interstitial injury was evaluated by a semi-quantitative histological scoring system after hematoxylin-eosin staining. The inferior vena cava blood samples were collected from rats in the 6 groups to measure the serum creatinine levels via sarcosine oxidase method, and serum urea nitrogen levels via urease method. The right renal cortices were collected from rats in the 6 groups to measure the catalase (CAT) activity in the supernatant of renal tissue via molybdic acid method, and the levels of advanced oxidation protein product (AOPP) and Klotho protein in the supernatant of renal tissue via enzyme-linked immunosorbent assay.Results:At PIH 8, 48, and 72 and PIW 1, the kidney/body weight ratios of rats in electric burn group were significantly higher than those in sham injury group (with t values of -0.52, -3.75, -4.05, and -2.25, respectively, P<0.05). At PIH 72, compared with those in electric burn group, saline group, low breviscapine group, and middle breviscapine group, the kidney/body weight ratio of rats in high breviscapine group was significantly decreased (with P values all <0.05). Compared with those in sham injury group, the renal tubular and renal interstitial injury scores of rats in electric burn group at PIH 48 and 72 and PIW 1 were significantly increased ( P<0.05). Compared with those in electric burn group at PIH 8 and 24, the renal tubular and renal interstitial injury score of rats in electric burn group at PIW 1 was significantly increased (with P values all <0.05). At PIH 72, the renal tubular and renal interstitial injury scores of rats in the 5 groups of rats with electric burns were similar ( P>0.05). At PIH 8, 24, 48, and 72 and PIW 1, the levels of serum creatinine and serum urea nitrogen of rats in electric burn group were significantly higher than those in sham injury group (with Z values of -2.00, -2.37, -2.62, -2.67, -3.67, -2.34, -3.11, -3.43, -3.11, and -3.51, respectively, P<0.05). Compared with that in electric burn group at PIH 0, the levels of serum creatinine of rats in electric burn group at PIH 72 and PIW 1 were significantly increased ( P<0.05). Compared with that in electric burn group at PIH 8, the levels of serum creatinine of rats in electric burn group at PIH 72 and PIW 1 were significantly increased ( P<0.05). Compared with that in electric burn group at PIH 24, the level of serum creatinine of rats in electric burn group at PIW 1 was significantly increased ( P<0.05). At PIH 72, the levels of serum creatinine of rats in the 5 groups of rats with electric burns were similar ( P>0.05). Compared with that in electric burn group, the levels of serum urea nitrogen of rats in low breviscapine group, middle breviscapine group, and high breviscapine group were significantly decreased ( P<0.05). Compared with that in saline group, the levels of serum urea nitrogen in middle breviscapine group and high breviscapine group were significantly decreased ( P<0.05). At PIH 48 and 72 and PIW 1, the CAT activities in the supernatant of renal tissue of rats in electric burn group were significantly lower than those in sham injury group (with Z values of -2.22, -2.13, and -3.51, respectively, P<0.05). At PIH 8, 24, 48, and 72 and PIW 1, the levels of AOPP in the supernatant of renal tissue of rats in electric burn group were significantly higher than those in sham injury group (with Z values of -2.00, -3.15, -2.71, -2.04, and -2.33, respectively, P<0.05). At PIH 0-PIW 1, the levels of Klotho protein in the supernatant of renal tissue of rats in sham injury group and electric burn group were all similar ( P>0.05). Compared with that in electric burn group at PIH 0, the CAT activities in the supernatant of renal tissue of rats in electric burn group at PIH 72 and PIW 1 and the levels of Klotho protein in the supernatant of renal tissue of rats in electric burn group at PIH 48 and 72 and PIW 1 were significantly decreased ( P<0.05). Compared with that in electric burn group at PIH 8, the CAT activities in the supernatant of renal tissue of rats in electric burn group at PIH 72 and PIW 1 and the levels of Klotho protein in the supernatant of renal tissue of rats in electric burn group at PIH 48 and 72 and PIW 1 were significantly decreased ( P<0.05). Compared with that in electric burn group at PIH 24, the CAT activities in the supernatant of renal tissue of rats in electric burn group at PIH 72 and PIW 1 were significantly decreased ( P<0.05). Compared with that in electric burn group at PIH 48, the CAT activity in the supernatant of renal tissue of rats in electric burn group at PIW 1 was significantly decreased ( P<0.05). At PIH 72, the levels of Klotho protein in the supernatant of renal tissue of rats in the 5 groups of rats with electric burns were similar ( P<0.05). Compared with 14.6 (12.6, 23.6) U/mgprot in electric burn group, the CAT activities in the supernatant of renal tissue of rats in low breviscapine group (20.5 (18.0, 39.8) U/mgprot), middle breviscapine group (24.9 (14.7, 28.9) U/mgprot), and high breviscapine group (28.0 (21.9, 39.1) U/mgprot) were significantly increased ( P<0.05). Compared with 15.7 (13.7, 25.6) U/mgprot in saline group, the CAT activities in the supernatant of renal tissue of rats in middle breviscapine group and high breviscapine group were significantly increased ( P<0.05). Compared with that in low breviscapine group, the CAT activity in the supernatant of renal tissue of rats in high breviscapine group was significantly increased ( P<0.05). Compared with those in electric burn group and saline group, the levels of AOPP in the supernatant of renal tissue of rats in middle breviscapine group and high breviscapine group were significantly decreased ( P<0.05). Conclusions:After high-voltage electric burns, oxidative stress injury occur in the kidneys of rats, which is aggravated with time extension. Breviscapine can alleviate oxidative stress injuries in the kidneys of rats with high-voltage electric burns.

Objective:To investigate the differences in estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and Ki-67 expressions between metastatic sites and primary sites in metastatic triple-negative breast cancer (TNBC) patients and to analyze their effects on the prognosis of patients.Methods:A retrospective cohort study was conducted. The clinicopathological data of 108 patients diagnosed with metastatic TNBC in Lianyungang Hospital Affiliated to Xuzhou Medical University from September 2018 to September 2023 were collected. Local metastatic sites included ipsilateral axillary lymph nodes and chest wall, while distant metastatic sites encompassed contralateral axillary lymph nodes and chest wall, bilateral supraclavicular lymph nodes, cervical lymph nodes, bone and viscera. The metastatic sites were identified as metastatic TNBC by using immunohistochemistry (IHC) and/or fluorescence in situ hybridization. The heterogeneity in ER, PR, HER2, and Ki-67 expression between primary sites and metastatic sites in all patients and those with local and distant metastases was analyzed, and the heterogeneity was defined as the inconsistency in the expression of markers including loss and gain expressions between primary sites and metastatic sites. The Kaplan-Meier method was used to analyze disease-free survival (DFS), and log-rank test was used for comparison among groups.Results:All patients were female, with an average age of (55±10) years; 51 cases had local metastases, and 57 cases had distant metastases. In metastatic sites, no ER and PR positivity were observed; in primary sites, 28.7% (31/108) of patients were ER positive and 21.3% (23/108) of patients were PR positive, and there were statistically significant differences in the proportion of patients with ER or PR positive between primary sites and metastatic sites (all P < 0.001). There were no statistically significant differences in the proportions of patients with different expression status including HER2 [positive: 0 (0/108) vs. 4.6%(5/108), low expression: 50.0% (54/108) vs. 45.4% (49/108), negative: 50.0% (54/108) vs. 50.0% (54/108)], Ki-67 [high expression: 86.1% (93/108) vs. 91.7% (99/108)] between metastatic sites and primary sites (all P > 0.05). The proportions of patients with inconsistent ER and PR expression between metastatic sites and primary sites were 28.7% (31/108) and 21.3% (23/108), respectively, all due to the expression loss in metastatic sites; the proportions of patients with inconsistent HER2 and Ki-67 expression between metastatic sites and primary sites were 42.6% (46/108) and 11.1% (12/108), respectively, with HER2 and Ki-67 expression loss of metastatic sites accounting for 22.2% (24/108) and 8.3% (9/108), respectively and expression gain accounting for 20.4% (22/108) and 2.8% (3/108), respectively. The proportions of patients with inconsistent ER [45.6% (26/57) vs. 9.8% (5/51)], PR [36.8% (21/57) vs. 3.9% (2/51)] and Ki-67 [17.5% (10/57) vs. 3.9% (2/51)] expression in distant metastatic sites and primary sites were higher than those with local metastatic sites and primary sites, and the differences were statistically significant (all P < 0.05). The proportions of patients with inconsistent HER2 between distant metastatic sites and primary sites and those with inconsistent HER2 between local metastatic sites and primary sites were 47.4% (27/57), 37.3% (19/51), respectively, and the difference was not statistically significant ( P = 0.300). Patients with inconsistent ER and Ki-67 expressions had better DFS than those with consistent expressions, with median DFS time of 30 months (95% CI: 22-40 months) vs. 22 months (95% CI: 22-24 months) for ER and 28 months (95% CI: 20-61 months) vs. 22 months (95% CI: 22-24 months) for Ki-67, and the differences were statistically significant (all P < 0.05). There were no significant differences in DFS between metastatic sites and primary sites with consistent expressions of PR and HER2 or not (all P > 0.05). Conclusions:There are differences in ER and PR expressions between primary sites and metastatic sites of metastatic TNBC patients, while the expressions of HER2 and Ki-67 seem to be no differences. The inconsistency of ER, PR and Ki-67 expressions with primary sites in distant metastatic sites are more common compared with in local metastatic sites. The differences in hormone receptor expression between primary sites and metastatic sites may impact patients' DFS.

Objective:To investigate the clinicopathological features,differential diagnosis,treatment and prognosis of Burkitt-like lymphoma with 11q aberration (BLL-11q).Methods:The clinical manifestations,histological morphology,immunophenotype and molecular genetic changes of 2 cases of BLL-11q admitted to the department of pathology of The First People's Hospital of Lianyungang in 2020 and 2021 were analyzed retrospectively,and the relevant literatures were reviewed.Results:Patients were found with right neck masses inadvertently and grew rapidly. They presented with localized disease with Ann Arbor stages IA and IIA. Microscopically, the normal structure of the lymph node disappeared and was replaced by a diffuse proliferation of lymphocytes, with consistent morphology and medium size. And the presence of "star-sky" phenomenon was obvious, the morphological characteristics were similar to Burkitt lymphoma. Immunophenotypically, tumor cells were diffusely positive for CD20, CD79α, PAX5, CD10 and Bcl-6, partly moderately positive for C-MYC and MUM-1, however, CD3, Bcl-2, CD30 and TDT were negative,Ki-67 positive index was more than 95%, and EBER was negative. FISH detection showed that MYC, Bcl-2, and Bcl-6 were negative. Both cases had the 11q23.3 gain and 11q24.3 loss. Both patients were treated with chemotherapy and followed up for 10-22 months,and achieved complete remission and disease-free survival.Conclusion:BLL-11q is a rare germinal center B-cell lymphoma with abnormal long arm of chromosome 11 and lack of MYC gene rearrangement. It should be distinguished from Burkitt lymphoma, diffuse large B-cell lymphoma, B-lymphoblastic lymphoma, large B-cell lymphoma with IRF4 rearrangement and high-grade B-cell lymphoma. On the basis of morphology and immunophenotype, the diagnosis depends on genetic detection. There may be a better prognosis.

Objective To investigate the clinicopathological and immunohistochemical features,diagnosis and prognosis of granular cell tumor of breast (GCT)and to improve the awareness of the disease.Methods Three cases of GCT were collected;Specimens were fully drawn,microscopic pathologic examinations and immunohistochemistry (SP method)were performed.Results Three cases were female patients aged from 39 to 56 years old (average 46 years).In clinical,a single indolent or indolent mass with a hard texture was located in the breast parenchyma.In pathological,the lump was mainly solid or hard tumor with clear boundary or infiltration,with a mean diameter of 2.1 (1.2-3.0)cm,and grey to yellow sections.Histologically,large cells were round or polygonal in shape.The cytoplasm was abundant and eosinophilic.The boundary of the tumor was clear in one case,and in the other two cases,the boundary was unclear.The nucleus was small and located in the center or ectopic.The cytoplasm was coarse-grained with s-100 staining positive microparticles and PAS reaction positive (anti-digestive enzymes).Immunohistochemistrically,the tumor cells were strongly positive for S-100,CD56,NSE and Vimentin,and negative for CK and SMA.None of the patients had present malignant transformation or metastasis.Conclusions GCT can occur in any part of the body,but is not common in breast.GCT is similar to breast cancer in clinical manifestations,imaging and macroscopic observation,etc.The correct diagnosis of this lesion depends on HE morphology,immunohistochemistry and special dyeing.The close postoperative follow-up should be performed.

BACKGROUND: To summarize the clinical features of patients with pulmonary embolism after lobectomy and to explore the methods of diagnosis and treatment of pulmonary embolism after lobectomy. METHODS: The clinical data of 6 patients with pulmonary embolism after lobectomy between July 2007 and July 2017 were retrospectively analyzed. RESULTS: Of the 6 patients, 3 died within 24 h of onset and 3 patients were cured and discharged. CONCLUSIONS Pulmonary embolism after lobectomy is a rare postoperative complication in thoracic surgery. It is difficult to diagnose and has a high mortality rate. Preoperative thromboembolic risk assessment and postoperative prevention are important.
Aged ; Female ; Humans ; Lung Neoplasms ; surgery ; Male ; Middle Aged ; Pneumonectomy ; adverse effects ; Postoperative Complications ; diagnosis ; etiology ; therapy ; Pulmonary Embolism ; diagnosis ; etiology ; therapy ; Retrospective Studies ; Thoracic Surgery, Video-Assisted ; adverse effects

Objective To provide theoretical basis for researchers and institutions to conduct research in stroke according the multiple dimension analysis of stroke research paper cooperation nationally.Methods Using the scientometrics and social network analysis for data mining of 95883 stroke literature collected.Results The result show that quantity of paper publishing are increasing annually,the most common cooperation was co-authorship of 2～3 people,cooperation among institutions mainly focused in big cities like Beijing,Shanghai,Guangzhou at its core has taken shape,regional cooperation formed a scattering cooperation with Beijing as the center,research topics has shifted from cognition and treatment to prognosis,rehabilitation and related chronic disease gradually.Conclusions It is necessary to expand the scale of coopreation in stroke study,policies encouraging cooperation should be adopted,strengthen regional cooperation between west China and middle-east,establish a multi-stage stroke unit and strengthen stroke treatment from the multi-level and multi-angle,pay more attention to the occurrence and development of chronic diseases associated with stroke.And finally,contribute to the further development of stroke research.

Objective To investigate the values of CD21 and CD43 proteins in the differential diagnosis of mucosa-associated marginal zone B-cell lymphoma (MALToma) from benign lymphadenosis. Methods The expression of CD21 and CD43 proteins in the tissues of 25 MALToma (case group) and 25 benign lymphadenosis (control group) was detected by immunohistochemistry. Results Abnormal CD21+follicular dendritic cells (FDC) meshes were found in all patients of case group. Most of the FDC meshes were sparse and broken, and a few were enlarged or fused into pieces. Intact CD21+FDC meshes were all found, and abnormal FDC meshes were not found in control group. The positive rate of abnormal FDC meshes in case group was significantly increased compared with that in control group (χ2 = 46.080, P= 0.000). The expression rate of CD43+in CD20+cells was 24 % (6/25) in case group, but it was negative in control group (χ2=4.375, P=0.030). Conclusions Abnormal CD21+FDC meshes and CD43+expression in CD20+cells are useful in the differential diagnosis between MALToma and benign lymphadenosis. The abnormal FDC meshes of MALToma are enlarged or fused in the minority of cases.