OBJECTIVE To explore the mechanism of Qiangxin decoction in the treatment of chronic heart failure （CHF） by regulating the inhibitor of nuclear factor-κB alpha/nuclear factor-κB p65 subunit （IκBα/NF-κB p65） signaling pathway-mediated M1 macrophage polarization. METHODS In animal experiments， mice were used as research subjects， and the CHF model was established via coronary artery ligation. Model mice were treated with Qiangxin decoction （21.69 g/kg） for 28 days. After intervention， pathological morphological changes of myocardial tissues and cardiomyocyte apoptosis were observed. Serum levels of inflammatory factors including tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6）， myocardial injury marker troponin I3 （TNNI3）， and macrophage-related markers F4/80 and cluster of differentiation 80 （CD80） were detected. In cell experiments， monocyte-macrophage leukemia RAW264.7 cells were induced to undergo M1 polarization by 10 ng/mL lipopolysaccharide combined with 10 ng/mL interferon-γ， followed by 48 h intervention with 10% drug-containing serum of Qiangxin decoction. After intervention， the nuclear translocation of NF-κB p65 and NF-κB p50 was observed. The positive rate of CD80 in cells was measured. The mRNA expression of inflammatory factors including IL-1β， IL-6， IL-8， IL-18， TNF-α， inducible nitric oxide synthase （iNOS）， cyclooxygenase-2 （COX2）， C-C motif chemokine receptor 7 isoform 2 （CCR7-2）， as well as the expression levels of proteins related to the IκBα/NF-κB p65 signaling pathway were detected. RESULTS Animal experimental results showed that Qiangxin decoction alleviated myocardial fibrosis in mice， and significantly reduced the cardiomyocyte apoptosis rate， serum levels of TNF-α and IL-6， as well as the protein expression of TNNI3， F4/80 and CD80 in myocardial tissues （P＜0.05）. Cell experimental results indicated that Qiangxin decoction significantly suppressed the nuclear translocation of NF-κB p65 and NF-κB p50 （P＜0.05）. It significantly decreased the CD80 positive rate， mRNA levels of IL-1β， IL-6， IL-8， IL-18， TNF-α， iNOS， COX2 and CCR7-2， total and nuclear expression of NF-κB p65， total， nuclear and cytoplasmic expression of phosphorylated NF-κB p65， total expression of phosphorylated IκBα （P＜0.05）. Meanwhile， it significantly elevated the total expression of IκBα and cytoplasmic expression of NF-κB p65 （P＜0.05）. CONCLUSIONS Qiangxin decoction can inhibit the activity of the IκBα/NF-κB p65 signaling pathway， reduce the release of pro-inflammatory factors， thereby restraining M1 macrophage polarization， mitigating myocardial fibrosis， and ultimately exerting therapeutic effects against CHF.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease lacking effective therapy. Metformin, an antidiabetic medication, has shown promising therapeutic properties in preclinical fibrosis models; however, its precise cellular targets and associated mechanisms in fibrosis resolution remain incompletely defined. Most research on metformin's effects has focused on mesenchymal and inflammatory responses with limited attention to epithelial cells. In this study, we utilized Sftpc lineage-traced and Fgfr2b conditional knockout mice, along with BMP2/PPARγ and AMPK inhibitors, to explore metformin's impact on alveolar epithelial cells in a bleomycin-induced pulmonary fibrosis model and cell culture. We found that metformin increased the proliferation and differentiation of alveolar type 2 (AT2) cells, particularly the recently identified injury-activated alveolar progenitors (IAAPs)-a subpopulation characterized by low SFTPC expression but enriched for PD-L1. Single-cell RNA sequencing revealed a reduction in apoptosis among mature AT2 cells. Interestingly, metformin's therapeutic effects were not significantly affected by BMP2 or PPARγ inhibition, which blocked the lipogenic differentiation of myofibroblasts. However, Fgfr2b deletion in Sftpc lineage cells significantly impaired metformin's ability to promote fibrosis resolution, a process linked to AMPK signaling. In conclusion, metformin alleviates fibrosis by directly activating AT2 cells, especially the IAAPs, through a mechanism that involves AMPK and FGFR2b signaling, but is largely independent of BMP2/PPARγ pathways.

Objective: To discover molecular markers associated with lung adenocarcinoma diagnosis/prognosis and drug resistance through screening of differentially expressed genes based on published chip data in gene expression databases using bioinformatics methods. Methods: Comprehensive analysis was performed in available mRNA microarray datasets including lung adenocarcinoma tissues dataset GSE32863 and lung adenocarcinoma taxane-platin resistance dataset GSE77209 from the gene expression omnibus(GEO) database. Gene ontology enrichment analysis, gene pathway enrichment analysis and protein interaction network analysis were performed based on significantly correlated genes. The expression level of genes was validated in the cancer genome atlas(TCGA) dataset. Survival differences were assessed by the log-rank test in TCGA lung adenocarcinoma dataset. Based on the publications genomics of drug sensitivity in cancer(GDSC) database in CellMiner cross database(CellMiner CDB), Pearson correlation analysis was used to analyze the correlation between differentially expressed genes and the half-maximal inhibitory concentration(IC50) of anticancer drugs. Results : There were a total of 77 genes which had a different expression in resistance lung adenocarcinoma cells and lung adenocarcinoma cancer tissues. The functional enrichment analysis showed that these co-different expression genes were mainly enriched in microtubule, extracellular exosome, cell cycle and signaling by nuclear receptors. Protein-protein interactions(PPI) network screened 6 most connected genes as molecular complex(MCODE). Among the MCODE, overexpressed ubiquitin conjugating enzyme E2 T(UBE2T), kinesin family member 20A(KIF20A), PCNA clamp associated factor(KIAA0101), pituitary tumor-transforming gene 1(PTTG1) and NIMA related kinase 2(NEK2) were associated with poor outcomes. Survival analysis results showed that these five genes were upregulated in lung adenocarcinoma tissues and drug-resistant cells and were significantly associated with poor prognosis in lung adenocarcinoma patients. Drug sensitivity analysis results suggested that high expression of PTTG1 and UBE2T was significantly associated with sensitivity to multiple anticancer drugs, including paclitaxel and docetaxel. RT-PCR validation showed that PTTG1 andUBE2T were highly expressed in docetaxel-resistant cells A549-TXR and H358-TXR. Conclusion PTTG1 andUBE2T holds the potential to be chemoresistance markers in lung adenocarcinoma.

Objective:To investigate the feasibility and clinical outcomes of using the deep inferior epigastric perforator flap to repair stage Ⅳ pressure ulcers in elderly patients with the femoral trochanter.Methods:Retrospective analysis of clinical data of elderly patients with stage Ⅳ pressure ulcers of the femoral trochanter treated at the Medical Center of Burn Plastic and Wound Repair, the First Affiliated Hospital of Nanchang University from May 2018 to May 2023 using the deep inferior epigastric perforator flap.The deep inferior epigastric perforator flap was designed on the same side of the abdomen based on the preoperative detection of the paraumbilical perforating branch.The axis of the inferior epigastric artery was determined by the line connecting the femoral artery pulsation point at the inguinal ligament and the obvious paraumbilical perforating branch point. The axis of the skin flap was determined by the line connecting the obvious paraumbilical perforating branch point and the subscapular angle. Combined with the situation of the sinus after pressure ulcer debridement and the range of skin and soft tissue defects, the inferior epigastric artery perforating branch skin flap was cut and repaired. The pedicle of the inferior epigastric artery was freed to the required length according to the location of the pressure ulcer, and the wound was transferred and repaired through a subcutaneous tunnel. The donor area was directly pulled and sutured. The survival of the skin flap and the healing of the donor site wound after surgery were observed, and the recurrence of pressure ulcers, the appearance and texture of the skin flap, and the recovery of the donor site were followed up regularly.Results:A total of 11 patients were included, including 7 males and 4 females; age ranged from 66 to 83 years old, with an average of 72.1 years old. There were total of 11 pressure ulcers in the femoral trochanter, with an area of 5.0 cm × 3.0 cm-13.0 cm ×6.0 cm before debridement and an area of 8.0 cm × 5.0 cm-16.0 cm × 8.0 cm after debridement. The deep inferior epigastric perforator flap was used to repair the wound. The flap was cut with an area of 10.0 cm × 6.0 cm-18.0 cm × 9.0 cm, and the length of the blood vessels in the flap pedicle was 12-16 cm, with an average of 14 cm. After surgery, 9 of the 11 flaps survived completely. One skin flap developed purplish discoloration at the distal end 24 hours after surgery, which was relieved by removing the suture at the site with high tension at the wound edge. One skin flap also showed slight necrosis at the distal end. The flap was removed under local anesthesia at the bedside of the ward, and the surgical wound was directly sutured. After dressing change, it healed. The wounds in the donor area all healed well. Follow up for 3-15 months postoperatively, with an average of 11 months, showed no recurrence of pressure ulcers in all patients. The skin flap had a soft texture, and its color and appearance were similar to those of the surrounding skin. No abdominal wall hernia was observed in the inferior epigastric donor area.Conclusion:The deep inferior epigastric perforator flap has a long vascular pedicle, reliable blood supply, sufficient tissue volume for cutting, no recurrence of pressure ulcers after surgery, good appearance and texture of the affected area, and no secondary abdominal wall hernia in the donor site. It is an effective method for repairing stage Ⅳ pressure ulcers of the femoral trochanter in elderly patients.

Objective:To investigate the feasibility and clinical outcomes of using the deep inferior epigastric perforator flap to repair stage Ⅳ pressure ulcers in elderly patients with the femoral trochanter.Methods:Retrospective analysis of clinical data of elderly patients with stage Ⅳ pressure ulcers of the femoral trochanter treated at the Medical Center of Burn Plastic and Wound Repair, the First Affiliated Hospital of Nanchang University from May 2018 to May 2023 using the deep inferior epigastric perforator flap.The deep inferior epigastric perforator flap was designed on the same side of the abdomen based on the preoperative detection of the paraumbilical perforating branch.The axis of the inferior epigastric artery was determined by the line connecting the femoral artery pulsation point at the inguinal ligament and the obvious paraumbilical perforating branch point. The axis of the skin flap was determined by the line connecting the obvious paraumbilical perforating branch point and the subscapular angle. Combined with the situation of the sinus after pressure ulcer debridement and the range of skin and soft tissue defects, the inferior epigastric artery perforating branch skin flap was cut and repaired. The pedicle of the inferior epigastric artery was freed to the required length according to the location of the pressure ulcer, and the wound was transferred and repaired through a subcutaneous tunnel. The donor area was directly pulled and sutured. The survival of the skin flap and the healing of the donor site wound after surgery were observed, and the recurrence of pressure ulcers, the appearance and texture of the skin flap, and the recovery of the donor site were followed up regularly.Results:A total of 11 patients were included, including 7 males and 4 females; age ranged from 66 to 83 years old, with an average of 72.1 years old. There were total of 11 pressure ulcers in the femoral trochanter, with an area of 5.0 cm × 3.0 cm-13.0 cm ×6.0 cm before debridement and an area of 8.0 cm × 5.0 cm-16.0 cm × 8.0 cm after debridement. The deep inferior epigastric perforator flap was used to repair the wound. The flap was cut with an area of 10.0 cm × 6.0 cm-18.0 cm × 9.0 cm, and the length of the blood vessels in the flap pedicle was 12-16 cm, with an average of 14 cm. After surgery, 9 of the 11 flaps survived completely. One skin flap developed purplish discoloration at the distal end 24 hours after surgery, which was relieved by removing the suture at the site with high tension at the wound edge. One skin flap also showed slight necrosis at the distal end. The flap was removed under local anesthesia at the bedside of the ward, and the surgical wound was directly sutured. After dressing change, it healed. The wounds in the donor area all healed well. Follow up for 3-15 months postoperatively, with an average of 11 months, showed no recurrence of pressure ulcers in all patients. The skin flap had a soft texture, and its color and appearance were similar to those of the surrounding skin. No abdominal wall hernia was observed in the inferior epigastric donor area.Conclusion:The deep inferior epigastric perforator flap has a long vascular pedicle, reliable blood supply, sufficient tissue volume for cutting, no recurrence of pressure ulcers after surgery, good appearance and texture of the affected area, and no secondary abdominal wall hernia in the donor site. It is an effective method for repairing stage Ⅳ pressure ulcers of the femoral trochanter in elderly patients.

Objective:To find the age-related indicators of human immune function in the blood, to explore the possibility to standardize the evaluation criterion of immune function in Chinese population.Methods:The peripheral blood samples from 478 healthy individuals with complete medical data collected at the Beijing Hospital from January 2019 to December 2019, were chosen and analyzed.The volunteers were divided into young(<40 years old)and elderly(≥70 years old)groups.The differences in RNA, cytokines and immune cell function(the proliferation of T cell as well as the ability of T cells and natural killer cells to lyse target cells)were compared between the young group versus the elderly group.Results:Real-time quantitative fluorescence RT-PCR detection method was used for detecting the following tumor immune-related genes in the peripheral blood of healthy people in young versus old groups: programmed death 1( PD1)gene, complement C3 gene( C3), complement C4 gene( C4), high sensitivity C-reactive protein gene( HsCRP), tumor necrosis factor alpha gene( TNFA), interferon gamma gene( INF- γ), interleukin-6 gene( IL-6), interleukin-8 gene( IL-8), cytotoxic T lymphocyte-associated antigen-4 gene( CTLA-4), nuclear transcription factor-κB gene( NF- κB), long intergenic noncoding RNA-erythroid pro-survival gene( lincRNA- EPS), long non-coding RNA-myeloid RNA regulator of Bim-induced death gene( lncRNA- Morrbid), lincRNA-cyclooxygenase 2 gene( lincRNA- Cox2), Lnc-Dendritic cells( Lnc- DC), and circRNA-7 gene( ciRS-7). The mRNA level of C4 was significantly lower in elderly people than in young controls[young group(1.01±0.18) vs.old group(0.64±0.13), P=0.047], while others showing a non-statistically significant difference( P>0.05). The protein levels of programmed death 1(PD1), complement C3(C3), complement C4(C4), high sensitivity C-reactive protein(HsCRP), tumor necrosis factor alpha(TNF-α), interferon gamma(INF-γ), interleukin-6(IL-6), interleukin-8(IL-8), cytotoxic T lymphocyte-associated antigen-4(CTLA-4)and nuclear transcription factor-κB(NF-κB)in plasma were detected by enzyme-linked immunosorbent assay(ELISA). The following protein levels were significantly higher in the elderly group than in the young group: IL-6 protein[young group(249.30±100.02)ng/L vs.old group(283.00±94.98)ng/L, P=0.021], HsCRP protein[young group(2543.00±1111.89)ng/L vs.old group(3056.00±1056.61)ng/L, P=0.002], INF-γ protein[young group(362.40±383.67)ng/L vs.old group(500.40±502.27)ng/L, P=0.047]and TNF-α protein[young group(20.74±29.47)ng/L vs.old group(33.09±48.91)ng/L, P=0.042]. While the level of C4 was significantly lower in the elderly group than in the young group[young group(449.50±51.17)ng/L vs.old group(407.10±59.78)ng/L, P<0.0001]. T-cell proliferation, quantified by flow cytometry-based fluorescent dye dilution, showed that the CD3 + T cells of elder people had proliferated through 4 generations, while the CD3 + T cells of young people had proliferated through 5 generations.As shown in the NK killing assays, the secretion of LDH in the target A549 tumor cells decreased significantly after treated with NK cells belonging to elder individuals.The result demonstrated that individuals over 70 years old have significantly lower levels of the killing activity of NK cells( P<0.05). However, there was not statistically significant in T lymphocyte killing activity between different ages( P>0.05). Conclusions:IL-6, HsCRP, INF-γ and TNF-α levels are increased with aging, while the level of C4 significantly is decreased.The proliferation ability of T cells and the ability of NK cells to kill tumor cells are weakened.

[摘 要] 目的：基于已发表的芯片数据通过生物信息学方法筛选差异表达基因，以发现前列腺癌诊断/预后和耐药相关分子标志物。方法：筛选GEO数据库中已发表的前列腺癌mRNA芯片数据GSE6956和前列腺癌细胞多烯紫杉醇耐药mRNA芯片数据GSE33455进行差异表达分析；通过生物学功能注释、基因通路富集分析、蛋白质相互作用网络（protein-protein interaction，PPI）分析等生物信息学方法发现和识别与差异表达基因相关的生物学功能和信号通路；比对TCGA数据库，验证差异表达基因在前列腺癌组织及癌旁组织中的表达，并通过Kaplan-Meier分析差异表达基因对前列腺癌患者生存率的影响；用qPCR方法验证差异表达基因在前列腺癌细胞株PC3及多烯紫杉醇耐药细胞PC3-DTX中的表达情况。结果：共筛选出227个在前列腺癌和前列腺癌多烯紫杉醇耐药细胞芯片数据中共同差异表达基因。差异表达基因主要富集到了癌症相关通路（Lysosome、Sphingolipid、FoxO、Acute myeloid leukemia），并主要参与细胞黏附、自噬和胞内蛋白转运等生物学过程。构建PPI网络选取18个连接度最高的基因作为Hub基因。Hub基因和共同差异表达基因中，上调基因CITED2、LRP12和RPL17-C18orf32与前列腺癌患者的不良预后显著相关。qPCR验证显示CITED2在多烯紫杉醇耐药细胞PC3-DTX中高表达。结论：通过生物信息学方法筛选出在前列腺癌组织和耐药细胞中共同差异表达，且与前列腺癌患者的不良预后密切相关的基因，为前列腺癌诊断/预后和耐药分子标志物的研究提供了新的思路。

PURPOSE: The significance of neuroendocrine differentiation (NED) in gastric carcinoma (GC) is controversial, leading to ambiguous concepts in traditional classifications. This study aimed to determine the prognostic threshold of meaningful NED in GC and clarify its unclear features in existing classifications. MATERIALS AND METHODS: Immunohistochemical staining for synaptophysin, chromogranin A, and neural cell adhesion molecule was performed for 945 GC specimens. Survival analysis was performed using the log-rank test and univariate/multivariate models with percentages of NED (PNED) and demographic and clinicopathological parameters. RESULTS: In total, 275 (29.1%) cases were immunoreactive to at least 1 neuroendocrine (NE) marker. GC-NED was more common in the upper third of the stomach. PNED, and Borrmann's classification and tumor, lymph node, metastasis stages were independent prognostic factors. The cutoff PNED was 10%, beyond which patients had significantly worse outcomes, although the risk did not increase with higher PNED. Tumors with ≥10% NED tended to manifest as Borrmann type III lesion with mixed/diffuse morphology and poorer histological differentiation; the NE components in this population mainly grew in insulae/nests, which differed from the predominant growth pattern (glandular/acinar) in GC with <10% NED. CONCLUSIONS: GC with ≥10% NED should be classified as a distinct subtype because of its worse prognosis, and more attention should be paid to the necessity of additional therapeutics for NE components.
Adenocarcinoma ; Chromogranin A ; Classification ; Humans ; Immunohistochemistry ; Lymph Nodes ; Neoplasm Metastasis ; Neural Cell Adhesion Molecules ; Prognosis ; Stomach ; Stomach Neoplasms ; Synaptophysin

Objective To explore the application of carbon nanoparticles for tracing sentinel node(SN) in early gastric cancer (EGC).Methods Forty-six patients with EGC conducted subserous injection of carbon nanoparticle solution 1.0 mL at 4-6 points around tumor during operation.SN was examined by adopting 3 different methods.The first stained lymph node was defined as the first SN(FSN),and the whole group lymph nodes were identified as the group SN(GSN) and all lymph nodes colored within 5 min were labeled as the all SN(ASN).The affirmative SN and other resected lymph nodes were performed the histopathological examination and comparison.Resnlts In all 46 cases,SN was successfully detected out with the detection rate of 100％;the number of SN,GSN and ASN were 1.04 ± 0.21,3.93-±-1.90 and 13.61 ± 4.36 respectively,the difference in SN number among 3 different methods had statistical significance(P＜0.05).The accuracy rates of FSN,GSN and ASN for judging perigastric lymph node metastasis status were 95.65％,100％ and 100％,respectively.Conclusion The carbon nanoparticles tracing SN in EGC has higher staining rate and higher accuracy for predicting lymph node metastasis;GSN has high accuracy,moreover has less trauma and is most suitable method for detecting SN.

Currently, clinical laboratories are developing towards two different directions .One is centralized laboratory with automated pipelines , and the other is highly integrated portable detection system.The latter evolved from an early single test device gradually to an integrated platform based on microfluidic technology , which can operate multiple steps and tests simultaneously .The microfluidic system is further developed to a miniaturized device which can perform biochemical , immune, microbial and cytological tests.With the medical reform process in China , the microfluidic systems will appear in the primary health unit or even families .This review concludes the current application of microfluidic technology in clinical diagnostics and its future trends .