Background Regulatory interactions between microRNAs (miRNAs) and messenger RNAs (mRNAs) are involved in the progression of pulmonary fibrosis, which can either promote or inhibit the development of this disease. Objective To explore the miRNA-mRNA regulatory network during the progression of silica (SiO₂)-induced pulmonary fibrosis in mice using integrated mRNA-seq and miRNA-seq analysis. Methods A mouse model of pulmonary fibrosis was established by dynamic SiO₂ dust exposure. The experimental design included a blank control group and four SiO₂-exposed groups (7, 14, 28, and 56 d, n=10 per group). Successful model induction was confirmed by histopathological analysis (HE and Masson staining), hydroxyproline (HYP) quantification, and expression of key fibrosis-related cytokines [fibroblast growth factor (FGF), interleukin-6 (IL-6), transforming growth factor-β (TGF-β), and tumor necrosis factor-α (TNF-α)]. Lung tissues from mice in each group were subjected to sequencing, and Mfuzz was used for time-series gene clustering to identify dynamic progression patterns. DESeq2 was utilized to identify differentially expressed genes (DEGs) and differentially expressed miRNAs. Enrichment analysis of DEGs was performed to identify critical signaling pathways and biological processes underlying pulmonary fibrosis progression. Expression of four selected miRNAs was subsequently validated by real-time quantitative polymerase chain reaction (RT-qPCR). The target mRNAs of key miRNAs were comprehensively predicted by integrating miRBase, starBase, and miRTarBase to construct the regulatory networks and investigate potential functions. Results SiO₂ exposure led to time-dependent aggravation of pulmonary fibrosis in mice, evidenced by increased fibrous deposition, elevated HYP levels (P < 0.01), and up-regulation of four kinds of pro-fibrotic cytokines (P < 0.01) compared with the NT group. Mfuzz clustering revealed the stage-specific characteristics. Compared to controls, 231, 662, 448, and 1020 DEGs were identified after SiO₂ exposure at 7, 14, 28, and 56 d, respectively, primarily enriched in immune responses and chemokine signaling. During critical fibrotic phases—7 d (acute inflammation and initiation) and 28 d (chronic inflammation and establishment)—18 differentially expressed miRNAs were identified; notably mmu-miR-135b-5p was significantly dysregulated at both time points. The expression trends of the four key miRNAs (mmu-miR-135b-5p, mmu-miR-708-5p, mmu-miR-21a-3p, and mmu-miR-205-5p) were consistent with the sequencing results. Furthermore, bioinformatics databases were used to predict the target mRNAs of key miRNAs. The constructed network highlighted critical miRNA-mRNA pairs—including mmu-miR-135b-5p and Meis1, mmu-miR-708-5p and Mmp25, mmu-miR-21a-3p and Cacna1d, mmu-miR-205-5p and Ereg which were closely associated with inflammatory response, extracellular matrix deposition, and fibroblast activation. Conclusion The progression of pulmonary fibrosis is accompanied by dynamic changes in miRNA-mRNA regulatory networks. The identified miRNA-target axes (e.g., miR-135b-5p and Meis1, mmu-miR-708-5p and Mmp25, mmu-miR-21a-3p and Cacna1d, and mmu-miR-205-5p and Ereg—) may play important roles in fibrogenesis and provide potential therapeutic targets for pulmonary fibrosis.

Background Regulatory interactions between microRNAs (miRNAs) and messenger RNAs (mRNAs) are involved in the progression of pulmonary fibrosis, which can either promote or inhibit the development of this disease. Objective To explore the miRNA-mRNA regulatory network during the progression of silica (SiO₂)-induced pulmonary fibrosis in mice using integrated mRNA-seq and miRNA-seq analysis. Methods A mouse model of pulmonary fibrosis was established by dynamic SiO₂ dust exposure. The experimental design included a blank control group and four SiO₂-exposed groups (7, 14, 28, and 56 d, n=10 per group). Successful model induction was confirmed by histopathological analysis (HE and Masson staining), hydroxyproline (HYP) quantification, and expression of key fibrosis-related cytokines [fibroblast growth factor (FGF), interleukin-6 (IL-6), transforming growth factor-β (TGF-β), and tumor necrosis factor-α (TNF-α)]. Lung tissues from mice in each group were subjected to sequencing, and Mfuzz was used for time-series gene clustering to identify dynamic progression patterns. DESeq2 was utilized to identify differentially expressed genes (DEGs) and differentially expressed miRNAs. Enrichment analysis of DEGs was performed to identify critical signaling pathways and biological processes underlying pulmonary fibrosis progression. Expression of four selected miRNAs was subsequently validated by real-time quantitative polymerase chain reaction (RT-qPCR). The target mRNAs of key miRNAs were comprehensively predicted by integrating miRBase, starBase, and miRTarBase to construct the regulatory networks and investigate potential functions. Results SiO₂ exposure led to time-dependent aggravation of pulmonary fibrosis in mice, evidenced by increased fibrous deposition, elevated HYP levels (P < 0.01), and up-regulation of four kinds of pro-fibrotic cytokines (P < 0.01) compared with the NT group. Mfuzz clustering revealed the stage-specific characteristics. Compared to controls, 231, 662, 448, and 1020 DEGs were identified after SiO₂ exposure at 7, 14, 28, and 56 d, respectively, primarily enriched in immune responses and chemokine signaling. During critical fibrotic phases—7 d (acute inflammation and initiation) and 28 d (chronic inflammation and establishment)—18 differentially expressed miRNAs were identified; notably mmu-miR-135b-5p was significantly dysregulated at both time points. The expression trends of the four key miRNAs (mmu-miR-135b-5p, mmu-miR-708-5p, mmu-miR-21a-3p, and mmu-miR-205-5p) were consistent with the sequencing results. Furthermore, bioinformatics databases were used to predict the target mRNAs of key miRNAs. The constructed network highlighted critical miRNA-mRNA pairs—including mmu-miR-135b-5p and Meis1, mmu-miR-708-5p and Mmp25, mmu-miR-21a-3p and Cacna1d, mmu-miR-205-5p and Ereg which were closely associated with inflammatory response, extracellular matrix deposition, and fibroblast activation. Conclusion The progression of pulmonary fibrosis is accompanied by dynamic changes in miRNA-mRNA regulatory networks. The identified miRNA-target axes (e.g., miR-135b-5p and Meis1, mmu-miR-708-5p and Mmp25, mmu-miR-21a-3p and Cacna1d, and mmu-miR-205-5p and Ereg—) may play important roles in fibrogenesis and provide potential therapeutic targets for pulmonary fibrosis.

Background/Aims: Biliary tract cancer (BTC) frequently harbors KRAS mutations, which are associated with resistance to traditional treatment and a poor prognosis. Synthetic lethality (SL) strategy may provide other targets of KRAS. Therefore, we aim to identify and validate potential therapeutic targets of KRAS for the treatment of BTC via SL. Methods: The dependency (DepMap) projects were used to predict the synthetic lethal gene of KRAS. FDA-approved anticancer drug library was applied to screen potential drugs effective against KRAS-mutant BTC. Furthermore, the synthetic lethal effects or corresponding mechanisms of potential genes and drugs on BTC were investigated using KRAS-mutant and KRAS-wild type BTC cell lines, patient-derived xenografts (PDX), and KRAS oncogene-driven tumor models, as well as other KRAS-mutant cancer cell lines. Results: Initially, we discovered that the loss of GATA2 reduced the viability of KRAS-mutant but not KRAS-wild-type BTC. Subsequently, the drug library screened out disulfiram, which primarily exerts a synthetic lethal effect by inhibiting interleukin-1β (IL-1β) in KRAS-mutant BTC. Mechanistically, GATA2 specifically enhanced the transcription of IL-1β to promote NF-κB signaling in KRAS-mutant BTC. IL-1β inhibition phenocopied GATA2 deficiency, leading to reduced KRAS-mutant BTC viability. These synthetically lethal effects were confirmed using PDX, a KRAS oncogene-driven tumor model, as well as in other KRAS-mutant cancer cell lines. Conclusions In summary, these results indicate that inhibiting GATA2/IL1β could be a therapeutic strategy in KRAS-mutant BTC and potentially other cancers.

OBJECTIVE To explore the relationship between peripheral blood interferon γ(IFN-γ)/interleukin-4(IL-4)and the short-term prognosis of children with Mycoplasma pneumoniae pneumonia(MPP),and to analyze the influencing factors for the short-term prognosis of children with MPP.METHODS A total of 170 children with MPP admitted to the hospital from Jan.2021 to Jan.2024 were selected(MPP group).Based on the condition 28 days after treatment,they were divided into a poor prognosis group(n=49)and a good prognosis group(n=121).Clinical data of the children were collected,and the levels of peripheral blood interleukin-4(IL-4)and inter-feron-γ(IFN-γ)were measured to calculate the IFN-γ/IL-4 ratio.Multivariate Logistic regression model was used to analyze the factors affecting the short-term prognosis of children with MPP.RESULTS In the poor prognosis group,the duration of antibiotic use,the proportion of pleural effusion,the proportion of extrapulmonary compli-cations,and the levels of peripheral blood IL-4 and IFN-γ were higher than those in the good prognosis group,while the IFN-γ/IL-4 ratio was lower than that in the good prognosis group(P＜0.05).Logistic regression re-sults showed that persistent fever,prolonged antibiotic use and the occurrence of extrapulmonary complications were risk factors for the short-term prognosis of children with MPP(P＜0.05),and a high IFN-γ/IL-4 ratio was a protective factor(P＜0.05).CONCLUSION Persistent fever,prolonged antibiotic use and extrapulmonary com-plications are risk factors for the short-term prognosis of children with MPP,and high IFN-γ/IL-4 values is a pro-tective factor.

OBJECTIVE To explore the relationship between peripheral blood interferon γ(IFN-γ)/interleukin-4(IL-4)and the short-term prognosis of children with Mycoplasma pneumoniae pneumonia(MPP),and to analyze the influencing factors for the short-term prognosis of children with MPP.METHODS A total of 170 children with MPP admitted to the hospital from Jan.2021 to Jan.2024 were selected(MPP group).Based on the condition 28 days after treatment,they were divided into a poor prognosis group(n=49)and a good prognosis group(n=121).Clinical data of the children were collected,and the levels of peripheral blood interleukin-4(IL-4)and inter-feron-γ(IFN-γ)were measured to calculate the IFN-γ/IL-4 ratio.Multivariate Logistic regression model was used to analyze the factors affecting the short-term prognosis of children with MPP.RESULTS In the poor prognosis group,the duration of antibiotic use,the proportion of pleural effusion,the proportion of extrapulmonary compli-cations,and the levels of peripheral blood IL-4 and IFN-γ were higher than those in the good prognosis group,while the IFN-γ/IL-4 ratio was lower than that in the good prognosis group(P＜0.05).Logistic regression re-sults showed that persistent fever,prolonged antibiotic use and the occurrence of extrapulmonary complications were risk factors for the short-term prognosis of children with MPP(P＜0.05),and a high IFN-γ/IL-4 ratio was a protective factor(P＜0.05).CONCLUSION Persistent fever,prolonged antibiotic use and extrapulmonary com-plications are risk factors for the short-term prognosis of children with MPP,and high IFN-γ/IL-4 values is a pro-tective factor.

As an important element of medical and health sector innovation, the translation of scientific and technological achievements plays a key role in promoting their clinical application and meeting the medical needs of the people. The authors sorted out the problems in such translation at these affiliated hospitals in terms of " people", " finance", " material", and " system". Starting from 2017, the Tenth People′s Hospital Affiliated to Tongji University has explored such practices as establishing hospital-led clinical medical science and technology innovation parks and technology service limited companies. These practices aimed to address the issues of insufficient hospital scientific and technological innovation capabilities and the gap between the hospital′s operation mechanism to translate its scientific and technological achievements and the enterprises and the market. The clinical medical science and technology innovation park integrating administration, industry, education, research, medicine and application, has taken multiple measures to attract excellent research talents and projects from within and beyond the hospital, promote the implementation of innovative scientific research projects. The hospital also established a health industry mode with engagement of social capital from large enterprises. The Technology Services Co., Ltd. was based on the incubation and translation of hospital achievements, combining market and clinical needs, promoting multi-party cooperation between hospitals and external enterprises, improving the chain operation mechanism of hospital scientific and technological achievements translation work, and alleviating the problem of insufficient research pilot funds and productibility funds by means of hospital-led fundraising. The number of patent authorizations of hospitals had increased from 23 cases in 2018 to 105 in 2022, and the amount of patent conversion had increased from 2 million yuan in 2020 to 11 million yuan in 2022. It is recommended that affiliated hospitals of universities further improve the organizational structure of achievement translation, strengthen their professional talent teams, improve their operation mechanism of achievement translation, build a platform for medical school-enterprise cooperation, and improve the evaluation mechanism of translation assessment, in order to promote a virtuous cycle of hospital′s scientific and technological achievement translation work.

In the context of non-alcoholic fatty liver disease (NAFLD), characterized by dysregulated lipid metabolism in hepatocytes, the quest for safe and effective therapeutics targeting lipid metabolism has gained paramount importance. Sanhuang Xiexin Tang (SXT) and Baihu Tang (BHT) have emerged as prominent candidates for treating metabolic disorders. SXT combined with BHT plus Cangzhu (SBC) has been used clinically for Weihuochisheng obese patients. This retrospective analysis focused on assessing the anti-obesity effects of SBC in Weihuochisheng obese patients. We observed significant reductions in body weight and hepatic lipid content among obese patients following SBC treatment. To gain further insights, we investigated the effects and underlying mechanisms of SBC in HFD-fed mice. The results demonstrated that SBC treatment mitigated body weight gain and hepatic lipid accumulation in HFD-fed mice. Pharmacological network analysis suggested that SBC may affect lipid metabolism, mitochondria, inflammation, and apoptosis-a hypothesis supported by the hepatic transcriptomic analysis in HFD-fed mice treated with SBC. Notably, SBC treatment was associated with enhanced hepatic mitochondrial biogenesis and the inhibition of the c-Jun N-terminal kinase (JNK)/nuclear factor-kappa B (NF-κB) and extracellular signal-regulated kinase (ERK)/NF-κB pathways. In conclusion, SBC treatment alleviates NAFLD in both obese patients and mouse models by improving lipid metabolism, potentially through enhancing mitochondrial biogenesis. These effects, in turn, ameliorate inflammation in hepatocytes.
Humans ; Mice ; Animals ; Non-alcoholic Fatty Liver Disease/metabolism* ; NF-kappa B/metabolism* ; Organelle Biogenesis ; Retrospective Studies ; Mice, Inbred C57BL ; Obesity/metabolism* ; Liver ; Inflammation/metabolism* ; Body Weight ; Lipid Metabolism ; Lipids ; Diet, High-Fat/adverse effects*

Objective:To explore the early outcomes surgical treatment with growing rod for idiopathic early-onset scoliosis (IEOS).Methods:Data of 11 patients with IEOS who had surgical treatment from February 2017 to December 2018 were retrospectively analyzed. There were 4 males and 7 females aged 6.45±1.63 at the time of the first operation, with preoperative Cobb angle of 74.74°±6.48° (range, 66.12°-87.85°). The imaging data and clinical data before operation, after operation instantly, 1 month after operation, 1 year after operation and 2 years after operation, and surgical-related complications were analyzed and recorded.Results:All the 11 patients were followed up for 28.82±4.77 months. The Cobb angle was 74.74°±6.48° before the initial implantation of internal fixation, and decreased to 30.30°±4.04° immediately after the operation, 30.39°±4.49° 1 month after the operation, 26.93°±3.09° 1 year after the operation, and 28.36°±2.98° 2 years after the operation. The correction rate was 61.82%±4.85% 2 years after operation. The height of T 1-T 12 thoracic vertebra was 13.69±2.05 cm before surgery, and increased to 20.74±3.10 cm immediately after surgery, and was 20.85±3.62 cm 1 month after surgery, 21.49±3.56 cm 1 year after surgery, and 22.54±3.63 cm 2 years after surgery. The height of T 1-S 1 vertebral body was 24.21±3.20 cm before surgery, and increased to 31.04±3.79 cm immediately after surgery, and was 30.85±3.64 cm 1 month after surgery, 32.91±3.24 cm 1 year after surgery, and 34.46±3.28 cm 2 years after surgery. Preoperative apical vertebral translation (AVT) was 7.45±2.00 cm before the initial operation, and shortened to 2.04±0.67 cm immediately after the operation, 2.07±0.70 cm 1 month after the operation, 2.24±0.57 cm 1 year after the operation, and 2.11±0.82 cm 2 years after the operation. There were statistically significant differences in the above indexes before surgery, 1 month after surgery, 1 year after surgery and 2 years after surgery. Compared with preoperation, pulmonary function FEV1 and FVC increased to 1.28±0.13 L and 1.49±0.10 L, respectively, 1 year after surgery, and 1.34±0.13 L and 1.54±0.12 L, respectively, 2 years after surgery. Pulmonary function was significantly improved 1 year after surgery, and pulmonary FVC was positively correlated with T 1-T 12 thoracic vertebral height ( r=0.838, P< 0.001). 13 complications were found in the 11 patients, including 2 cases of proximal screws loosening, 1 case of proximal junction kyphosis, 1 case of titanium rod fracture, 3 cases of skin swelling cause by internal fixation, and 6 cases of subcutaneous effusion, with good results after timely treatment. Conclusion:The traditional growing rod can effectively control the progression of deformity in patients with IEOS, maintain the growth and development of trunk, and promote the development and maturation of lung function.

Objective    To evaluate the effectiveness of the artificial intelligence-assisted diagnosis and treatment system in distinguishing benign and malignant lung nodules and the infiltration degree. Methods    Clinical data of 87 patients with pulmonary nodules admitted to the First Affiliated Hospital of Xiamen University from January 2019 to August 2020 were retrospectively analyzed, including 33 males aged 55.1±10.4 years, and 54 females aged 54.5±14.1 years. A total of 90 nodules were included, which were divided into a malignant tumor group (n=80) and a benign lesion group (n=10), and the malignant tumor group was subdivided into an invasive adenocarcinoma group (n=60) and a non-invasive adenocarcinoma group (n=20). The malignant probability and doubling time of each group were compared and its ability to predict the benign and malignant nodules and the invasion degree was analyzed. Results    Between the malignant tumor group and the benign lesion group, the malignant probability was significantly different, and the malignant probability could better distinguish malignant nodules and benign lesions (87.2%±9.1% vs. 28.8%±29.0%, P=0.000). The area under the curve (AUC) was 0.949. The maximum diameter of nodules in the benign lesion group was significantly longer than that in the malignant tumor group (1.270±0.481 cm vs. 0.990±0.361 cm, P=0.026); the doubling time of benign lesions was significantly longer than that of malignant nodules (1 083.600±258.180 d vs. 527.025±173.176 d, P=0.000), and the AUC was 0.975. The maximum diameter of the nodule in the invasive adenocarcinoma group was longer than that of the non-invasive adenocarcinoma group (1.350±0.355 cm vs. 0.863±0.271 cm, P=0.000), and there was no statistical difference in the probability of malignancy between the invasive adenocarcinoma group and the non-invasive adenocarcinoma group (89.7%±5.7% vs. 86.4%±9.9%, P=0.082). The AUC was 0.630. The doubling time of the invasive adenocarcinoma group was significantly shorter than that of the non-invasive adenocarcinoma group (392.200±138.050 d vs. 571.967±160.633 d, P=0.000), and the AUC was 0.829. Conclusion    The malignant probability and doubling time of lung nodules calculated by the artificial intelligence-assisted diagnosis and treatment system can be used in the assessment of the preoperative benign and malignant lung nodules and the infiltration degree.

Acute respiratory failure due to acute hypoxemia is the major manifestation in severe coronavirus disease 2019 (COVID-19). Rational and effective respiratory support is crucial in the management of COVID-19 patients. High-flow nasal cannula (HFNC) has been utilized widely due to its superiority over other non-invasive respiratory support techniques. To avoid HFNC failure and intubation delay, the key issues are proper patients, timely application and improving compliance. It should be noted that elder patients are vulnerable for failed HFNC. We applied HFNC for oxygen therapy in severe and critical ill COVID-19 patients and summarized the following experiences. Firstly, to select the proper size of nasal catheter, to locate it at suitable place, and to confirm the nose and the upper respiratory airway unobstructed. Secondly, an initial ow of 60 L/min and 37℃ should be given immediately for patients with obvious respiratory distress or weak cough ability; otherwise, low-level support should be given first and the level gradually increased. Thirdly, to avoid hypoxia or hypoxemia, the treatment goal of HFNC should be maintained the oxygen saturation (SpO) above 95% for patients without chronic pulmonary disease. Finally, patients should wear a surgical mask during HFNC treatment to reduce the risk of virus transmission through droplets or aerosols.
Aged ; Betacoronavirus ; isolation & purification ; Cannula ; Coronavirus Infections ; therapy ; Humans ; Oxygen ; administration & dosage ; Pandemics ; Pneumonia, Viral ; therapy