Chemotherapy is currently the mainstay of systemic management for triple-negative breast cancer (TNBC), but chemoresistance significantly impacts patient outcomes. Our research indicates that Doxorubicin (Dox)-resistant TNBC cells exhibit increased glycolysis and ATP generation compared to their parental cells, with this metabolic shift contributing to chemoresistance. We discovered that ALKBH3, an m¹A demethylase enzyme, is crucial in regulating the enhanced glycolysis in Dox-resistant TNBC cells. Knocking down ALKBH3 reduced ATP generation, glucose consumption, and lactate production, implicating its involvement in mediating glycolysis. Further investigation revealed that aldolase A (ALDOA), a key enzyme in glycolysis, is a downstream target of ALKBH3. ALKBH3 regulates ALDOA mRNA stability through m¹A demethylation at the 3'-untranslated region (3'UTR). This methylation negatively affects ALDOA mRNA stability by recruiting the YTHDF2/PAN2-PAN3 complex, leading to mRNA degradation. The ALKBH3/ALDOA axis promotes Dox resistance both in vitro and in vivo. Clinical analysis demonstrated that ALKBH3 and ALDOA are upregulated in breast cancer tissues, and higher expression of these proteins is associated with reduced overall survival in TNBC patients. Our study highlights the role of the ALKBH3/ALDOA axis in contributing to Dox resistance in TNBC cells through regulation of ALDOA mRNA stability and glycolysis.

Objective:To explore the airway pathogen characteristics and examine the correlation between donor-derived pathogens and post-transplant outcomes in patients after lung transplantation (LT).Methods:Between January 1, 2015 and December 31, 2019, retrospective review was conducted for clinical and microbiological data of 88 LT recipients.Airway pathogen percentage of different microorganisms and evolution of drug-resistance were examined.Drug-resistant pathogen positive group (n=71) and negative group (n=17) were assigned according to whether or not drug-resistant pathogens were detected.Survival analysis was conducted by Log-rank with 3-year follow-ups.Between April 11, 2020 and September 5, 2020, prospective study was conducted in 14LT recipients.The potential pathogenic bacteria from donor lungs were detected by metagenomic next generation sequencing and the impact of those bacteria was examined on 1-year post-transplantation outcome in 2020.Microbial diversity and richness were shown with Shannon index.The outcome variables included heart rate, neutrophil count, lymphocyte count, immunoglobulin level and pulmonary spirometry.ANOVA and Pearson's correlation analysis were performed for elucidating the relationship between airway microbiota and post-LT outcomes.Results:From 2015 to 2019, 88 recipients were recruited and 992 strains of airway pathogens were isolated, including bacteria 796 strains and fungi 196 strains.Gram-negative bacteria (704 strains) accounted for 88.4% of all bacteria.The detection rates of Gram-positive bacteria, Klebsiella pneumonia (Kp), Acinetobacter baumannii (Ab), Stenotrophomonas maltophilia and Candida increased in 2019 than that in 2015 (8.2% vs. 5.3%, 13.6% vs. 13.2%, 33.2% vs. 17.5%, 6.5% vs. 5.3%, 26.6% vs. 20.2%). Drug resistance rate of Kp to imipenem was 68.18% in 2019 and drug resistance rate of Ab to imipenem 98.44%.The 3-year survival rate was 46.3% and 35.3% in drug-resistance positive and negative groups and the difference was insignificant ( P=0.410). Fourteen recipients were enrolled in 2020.Potential pathogenic bacteria could be detected in all donor samples.Five recipients carried the same bacteria and two died during 1-year follow-up.Nine recipients did not carry the donor-derived pathogens and two died during 1-year follow-up.The diversity of donor/recipient-derived airway microbiota (Shannon index) showed no correlation with the outcomes of 1-year follow-up by Pearson's correlation test. Conclusions:Gram-negative bacteria predominated in airway pathogens of recipients post-LT.The drug resistance rate to imipenem remained high.The donor/recipient-derived pathogen isolates showed no correlation with immediate outcomes post-LT.

Objective To investigate the mechanism of action of Xiaochaihu decoction in the treatment of hepatitis B based on network pharmacology. Methods The TCMSP database was used to obtain the main chemical components and action targets of the seven traditional Chinese medicines in Xiaochaihu decoction; the GeneCards and OMIM databases were used to obtain the targets associated with hepatitis B; the STRING online platform was used to construct a PPI network of potential targets, and R language was used to perform gene ontology (GO) functional enrichment analysis and KEGG pathway analysis; Cytoscape 3.7.2 was used to construct an "active component-core target" network and perform a topology analysis of this network; AutoDock vina and related software were used to perform molecular docking and visualized analysis of the active components with high value and the core targets in the network. Results A total of 193 main chemical components (including quercetin, kaempferol, wogonin, and naringenin) and 247 related targets were screened out, among which the key targets included RELA, MAPK1, TP53, ESR1, EGFR, and AKT1. A total of 2612 enrichment items were obtained by GO functional enrichment analysis, which were mainly involved in regulating the biological processes such as cell response to chemical stress, response to drugs, oxidative stress response, and lipopolysaccharide response. A total of 174 pathways were obtained by the KEGG pathway analysis, mainly involving hepatitis B, PI3K-AKT signaling pathway, and MAPK signaling pathway. Molecular docking results showed that the main active components had strong binding force to core targets, and the protein crystal complex had a stable conformation. Conclusion This study preliminarily shows that Xiaochaihu decoction exerts a therapeutic effect on hepatitis B through multiple components, targets, and pathways.

Objective To collect the incidence and distribution of congenital malformations ,find monitor-ing and preventive measures,to provide a basis for reasonable allocation of health resources for clinical depart-ments. Methods According to The International Classification of Diseases(ICD-10)chapter 17 encoding table, we analyze our hospital′s cases from January 2003 to December 2010 in order to understand the incidence of con-genital malformations of every system. Results Top five diseases are:cleft palate deformity ,genital malforma-tion,congenital heart disease and digestive system malformation in equal third place,and facial deformity. The age ranged from 1d to 35 y,men more than women. Conclusions The key to effectively reduce the incidence of con-genital malformation is strictly implement the three-level intervention mechanism. Prevention ,early detection and early treatment will improve the patient′s quality of life.

Objective: To compare amplification refractory mutation system(ARMS) and droplet digital PCR (ddPCR) in the detection of epidermal growth factor receptor (EGFR) gene mutations in patients with non-small cell lung cancer (NSCLC), and to investigate the clinical value of ddPCR. Methods: A total of 79 specimens of NSCLC, including 22 cases of cell block, 18 cases of surgical specimens, 12 cases of biopsy specimens and 27 cases of plasma samples, were analyzed for the mutation status of EGFR gene by ARMS and droplet digital PCR method. Results: In 18 cases of surgical specimens and 12 cases of biopsy specimens, the detection results by the two methods were identical with positive rates of 9/18 and 5/12, respectively. In 22 cases of effusion cell blocks, ARMS detected 19-del and L858R of EGFR gene in two cases, in which droplet digital PCR detected 19-del+ T790M mutations in one case and L858R+ T790M mutation in another. L858R mutation was detected by droplet digital PCR in one case but ARMS assay was negative. The remaining 19 cases were consistent by the two methods. In blood samples, the positive rate was 33.3%(9/27) by ARMS and 37.0%(10/27) by droplet digital PCR. Two cases showed L858R and 19-del+ T790M mutation by droplet digital PCR but ARMS assay detected only 19-del. The remaining 25 cases were consistent by the two methods. Conclusion Droplet digital PCR method is more sensitive and accurate than ARMS for the detection of EGFR mutations in pleural fluid and blood samples, can be used in clinical test.

OBJECTIVETo study the clinicopathologic characteristics of primary renal hemangioblastoma.

METHODSThe morphologic features, immunophenotype and molecular findings of 3 cases of primary renal hemangioblastoma were studied, with review of literature.

RESULTSThe age of patients ranged from 43 to 57 years. There were 2 women and a man. The patients often presented with renal mass. Histologically, the tumors were surrounded by thick fibrous capsule and composed of epithelioid or spindle cells. Two cases had a prominent stromal component and the other one was rich in capillary network. Lipid vacuoles were observed in all cases. Features of hemorrhage were demonstrated in 2 cases. Capsular invasion and necrosis were seen in 1 case. Immunohistochemical study showed that the stromal cells were positive for alpha-inhibin (3/3), S-100 protein (3/3), EGFR (2/2), PAX-2 (2/2), PAX-8 (2/2) and CA9 (2/2) but negative for CKpan (2/2) and HMB45 (2/2). Focal membranous staining for CD10 (3/3) was noted. No VHL gene mutations or chromosome 3p deletion were detected in the 2 cases studied.

CONCLUSIONSRenal hemangioblastoma shows distinctive morphologic appearance with a wide range of variation. The unexpected positive staining for PAX-2, PAX-8 and CD10 in renal hemangioblastoma needs to be aware. Immunohistochemical study may be helpful in differential diagnosis of these renal tumors.

Objective To study the clinicopathologic characteristics of primary renal hemangioblastoma.Methods The morphologic features, immunophenotype and molecular findings of 3 cases of primary renal hemangioblastoma were studied, with review of literature.Results The age of patients ranged from 43 to 57 years.There were 2 women and a man.The patients often presented with renal mass.Histologically, the tumors were surrounded by thick fibrous capsule and composed of epithelioid or spindle cells.Two cases had a prominent stromal component and the other one was rich in capillary network. Lipid vacuoles were observed in all cases.Features of hemorrhage were demonstrated in 2 cases.Capsular invasion and necrosis were seen in 1 case.Immunohistochemical study showed that the stromal cells were positive for alpha-inhibin (3/3), S-100 protein (3/3), EGFR (2/2), PAX-2 (2/2), PAX-8 (2/2) and CA9 (2/2) but negative for CKpan (2/2) and HMB45 (2/2).Focal membranous staining for CD10 (3/3) was noted.No VHL gene mutations or chromosome 3p deletion were detected in the 2 cases studied. Conclusions Renal hemangioblastoma shows distinctive morphologic appearance with a wide range of variation.The unexpected positive staining for PAX-2, PAX-8 and CD10 in renal hemangioblastoma needs to be aware.Immunohistochemical study may be helpful in differential diagnosis of these renal tumors.

OBJECTIVETo investigate the clinicopathologic features, immunohistochemic phenotypes and genetic alterations of extrapulmonary inflammatory myofibroblastic tumor (IMT) and the correlation with prognosis.

METHODSThirty cases of IMT with follow-up were analyzed morphologically and immunohistochemically. ALK FISH was also performed to determine the ALK gene status.

RESULTSPatients ranged in age from 12 to 73 years (mean 43.4 years). The male-to-female ratio was 1.0: 1.1. The tumors were located in various anatomical sites including gastrointestinal tract, liver, spleen, kidney, pelvic, retroperitoneum, mediastinum etc. Histologically, the majority of cases were composed of spindled fibroblastic and myofibroblastic cells accompanied by an inflammatory infiltrate of plasma cells, lymphocytes, and eosinophils. Most cases with aggressive behavior had features including prominent nucleoli and edematous myxoid background. Lymphohistiocytic reactions were usually absent. Some cases showed multinucleation, nuclear pleomorphism and mitoses. One case demonstrated epithelioid morphology with round-to-epithelioid cells. The immunohistochemical study showed vimentin, SMA, CK, desmin, and ALK were expressed in 100% (30/30), 70% (21/30), 13% (4/30), 27% (8/30), and 27% (8/30) of IMT, respectively. Diffuse cytoplasmic ALK staining was detected in seven cases. One case (containing round-to-epithelioid cells) demonstrated ALK nuclear membrane staining, coupled with positive reaction for CD30 and negative reaction for LCA. EMA, CD34, CD117 and S-100 protein, and MyoD1 were negative for all cases. Six ALK protein positive cases harbored ALK gene rearrangement, but not the remaining 22 cases. Follow-up data were available in 21 patients. After initial resection, 14 patients were alive with no evidence of disease, while 4 patients were alive with tumor recurrence and 3 patients died of the disease.

CONCLUSIONSMost IMT with aggressive behavior have features including prominent nucleoli, edematous myxoid background, and positive expression of ALK. Lymphohistiocytic reaction is usually absent. ALK may be a potential novel therapeutic target for IMT.

Adolescent ; Adult ; Aged ; Child ; Female ; Fibroblasts ; pathology ; Granuloma, Plasma Cell ; genetics ; pathology ; Humans ; Inflammation ; pathology ; Male ; Middle Aged ; Myofibroblasts ; pathology ; Prognosis ; Receptor Protein-Tyrosine Kinases ; genetics ; Young Adult

OBJECTIVETo study the clinicopathological features, differential diagnosis and prognosis of clear cell papillary renal cell carcinoma (CCPRCC).

METHODSThe histological, immunohistochemical, and molecular features were studied in 11 cases and follow-up data were also analyzed.

RESULTSThere were a total of 3 females and 8 males. The age of patients were ranged from 33 to 72 years(mean age 52.5 years). The diameters of tumors varied from 1cm to 4 cm. Histologically, papillary and cystic architecture were present at least focally in all tumors. The papillae were covered by small to medium-sized cuboidal cells with abundant clear cytoplasm and often showed extensive secondary branching, which were often folded and densely packed, resulting in a solid appearance. The nuclei were round and uniform in shape; nucleoli were not prominent (Fuhrman grade 1 or 2). Neither mitotic figures nor necrosis was present. All 11 cases exhibited moderate to strong positivity for CK7, CA9, vimentin, and HIF-1α, coupled with negative reactions for CD10, P504S, and TFE3. Ksp-cadherin was positively expressed in 8 cases.VHL gene mutations were not found in all 11 cases. Losses of chromosomes 3 (monoploid chromosome 3) was detected in 3 cases.

CONCLUSIONSCCPRCC is uncommon and seemed to be an indolent tumor. The differential diagnosis should be included tumors, which harbor clear cell and papillary structure including clear cell renal cell carcinoma, papillary renal cell carcinoma, Xp11 translocation renal cell carcinoma, and CCPRCC. Immunohistochemical and molecular analysis may be help for its diagnosis.

Adult ; Aged ; Carcinoma, Renal Cell ; chemistry ; genetics ; pathology ; ultrastructure ; Chromosomes, Human, Pair 3 ; Female ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; analysis ; Kidney Neoplasms ; chemistry ; genetics ; pathology ; ultrastructure ; Male ; Middle Aged ; Mutation ; Prognosis ; Racemases and Epimerases ; analysis ; Translocation, Genetic ; Tumor Burden

Objective To summarize the experience of nursing patients undergoing NovaSure endometrial ablation. Methods Two hundred and eleven patients with abnormal uterine bleeding claiming no need of giving birth,who were hospitalized in our hospital during August 2011 to April 2013,were managed with NovaSure endometrial ablation and nursing care was performed.Follow-ups were conducted for investigating the curative effects.Results All the patients lived through the operations,their life signs were stable.As for the adverse effects,124 of them had mild abdominal pains,7 medium-level or severe hypogastralgia,1 dizziness and nausea,10 uterial hematocele,and 1 cystitis.All of them got recovered after treatment.One-month follow-up after hospitalization showed a success rate of 98.0%.Conclusions NovaSure is a new approach to abnormal uterine bleeding.It is advantageous for its simplicity,shortness in operation duration,less trauma to patients and good effects.Meanwhile,preoperative mental care and cooperative care during operation may facilitate their recoveries.