Machine learning model based on RCA-PDCA nursing methods and differentiating factors to predict hypotension during cesarean section surgery.

BACKGROUND: Intraoperative hypotension during cesarean section has become a serious complication for maternal and fetal healthy. It is commonly encountered by subarachnoid anesthesia. However, currently used control methods have varying degrees of side effects, such as drugs. The Root Cause Analysis (RCA) - Plan, Do, Check, Act (PDCA) is a new model of care that identifies the root causes of problems. The study aimed to demonstrate the usefulness of RCA-PDCA nursing methods in preventing intraoperative hypotension during cesarean section and to predict the occurrence of intraoperative hypotension through a machine learning model. METHODS: Patients who underwent cesarean section at Traditional Chinese Medicine of Southwest Medical University from January 2023 to December 2023 were retrospectively screened, and the data of their gestational times, age, height, weight, history of allergies, intraoperative vital signs, fetal condition, operative time, fluid out and in, adverse effects, use of vasopressor drugs, anxiety-depression-pain scores, and satisfaction were collected and analyzed. The statistically different features were screened and five machine learning models were used as predictive models to assess the usefulness of the RCA-PDCA model of care. RESULTS: (1) Compared with the general nursing model, the RCA-PDCA nursing model significantly reduces the incidence of intraoperative hypotension and postoperative complications in cesarean delivery, and the patient experience is comfortable and satisfactory. (2) Among the five machine learning models, the RF model has the best predictive performance, and the accuracy of the random forest model in preventing intraoperative hypotension is as high as 90%. CONCLUSION: Through computer machine learning model analysis, we prove the importance of the RCA-PDCA nursing method in the prevention of intraoperative hypotension during cesarean section, especially the Random Forest model which performed well and promoted the application of artificial intelligence computer learning methods in the field of medical analysis.

Iron-Catalyzed Photochemical Synthesis of Sulfinamides from Aliphatic Hydrocarbons and Sulfinylamines.

An iron-catalyzed photochemical sulfinamidation of hydrocarbons with N-sulfinylamines has been developed. The merger of ligand-to-metal charge transfer (LMCT) of FeCl3 with hydrogen atom transfer (HAT) process is the key for the generation of alkyl radicals from hydrocarbons, and the resultant alkyl radicals were readily trapped by N-sulfinylamines to produce structurally diverse sulfinamides. Contrary to traditional methods that inevitably use sensitive organometallic reagents and prefunctionalized substrates, our approach features simple operation and the wide availability of starting materials. Gratifyingly, the reaction is scalable, and the obtained sulfinamides can be conveniently converted to highly functionalized sulfur(VI) derivatives.

Formation of Volatile Pyrazinones in Amadori Rearrangement Products and Maillard Reaction Systems and the Major Formation Pathways.

Amadori rearrangement products (ARPs) are gaining more attention for their potential usage in the food flavor industry. Peptide-ARPs have been studied, but pyrazinones that were theoretically found in the Maillard reaction (MR) have not been reported to be formed from small peptide-ARPs. This study found four pyrazinones: 1-methyl-, 1,5-dimethyl-, 1,6-dimethyl-, and 1,5,6-trimethyl-2(1H)-pyrazinones in both MR and ARP systems. It was the first time 1-methyl-2(1H)-pyrazinone was reported, along with 1,5-dimethyl- and 1,5,6-trimethyl-2(1H)-pyrazinones being purified and analyzed by nuclear magnetic resonance for the first time. The primary formation routes of the pyrazinones were also proven as the reaction between diglycine and α-dicarbonyls, including glyoxal, methylglyoxal, and diacetyl. The pyrazinones, especially 1,5-dimethyl-2(1H)-pyrazinone, have strong fluorescence intensity, which may be the reason for the increase of fluorescence intensity in MR besides α-dicarbonyls. Cytotoxicity analysis showed that both Gly-/Digly-/Trigly-ARP and the three pyrazinones [1-methyl-, 1,5-dimethyl-, and 1,5,6-trimethyl-2(1H)-pyrazinones] showed no prominent cytotoxicity in the HepG2 cell line below 100 µg/mL, further suggesting that ARPs or pyrazinones could be used as flavor additives in the future. Further research should be conducted to investigate pyrazinones in various systems, especially the peptide-ARPs, which are ubiquitous in real food systems.

Effect of spirocyclopiperazinium salt compound LXM-15 on spinal nerve injury in rats.

BACKGROUND: Currently available therapies for neuropathic pain show limited efficacy. This study aimed to investigate the anti-nociceptive effect of the spirocyclopiperazinium salt compound LXM-15 in spinal nerve ligation (SNL) rats and to explore the potential mechanisms. METHODS: Mechanical allodynia and thermal hyperalgesia tests were used to evaluate the effects of LXM-15 in SNL rats. The expression of CaMKIIα, CREB, JAK2, STAT3, c-fos and TNF-α was detected by western blotting, ELISA or qRT-PCR analysis. Receptor blocking test was performed to explore possible target. RESULTS: Administration of LXM-15 (1, 0.5, 0.25 mg/kg, i.g.) dose-dependently attenuated mechanical allodynia and thermal hyperalgesia in rats subjected to SNL (p < 0.01, p < 0.05), and the effects were completely blocked by peripheral α7 nicotinic or M4 muscarinic receptor antagonist (p > 0.05). LXM-15 significantly decreased the overexpression of phosphorylated CaMKIIα, CREB, JAK2 and STAT3 proteins and the mRNA levels of TNF-α and c-fos (p < 0.01, p < 05). All of the effects could be blocked by α7 or M4 receptor antagonist. Furthermore, LXM-15 reduced the protein expression of TNF-α and c-fos (p < 0.01, p < 0.05). No significant acute toxicity or abnormal hepatorenal function was observed. CONCLUSIONS: This is the first study to report that LXM-15 exerts significant anti-nociceptive effect on SNL rats. This effect may occur by activating peripheral α7 nicotinic and M4 muscarinic receptors, further inhibiting the CaMKIIα/CREB and JAK2/STAT3 signalling pathways, and finally inhibiting the expression of TNF-α and c-fos. SIGNIFICANCE: Existing treatments for neuropathic pain show limited efficacy with severe adverse reactions. This paper is the first to report that LXM-15, a new spirocyclopiperazinium salt compound, exerts a significant anti-nociception in SNL rats without obvious toxicity. The underlying mechanisms include activating peripheral α7 nicotinic and M4 muscarinic receptors, then inhibiting the signalling pathways of CaMKIIα/CREB and JAK2/STAT3 and the expressions of TNF-α and c-fos. This study sheds new light on the development of novel analgesic drugs with fewer side effects.

HK2 in microglia and macrophages contribute to the development of neuropathic pain.

Neuropathic pain is a complex pain condition accompanied by prominent neuroinflammation involving activation of both central and peripheral immune cells. Metabolic switch to glycolysis is an important feature of activated immune cells. Hexokinase 2 (HK2), a key glycolytic enzyme enriched in microglia, has recently been shown important in regulating microglial functions. Whether and how HK2 is involved in neuropathic pain-related neuroinflammation remains unknown. Using a HK2-tdTomato reporter line, we found that HK2 was prominently elevated in spinal microglia. Pharmacological inhibition of HK2 effectively alleviated nerve injury-induced acute mechanical pain. However, selective ablation of Hk2 in microglia reduced microgliosis in the spinal dorsal horn (SDH) with little analgesic effects. Further analyses showed that nerve injury also significantly induced HK2 expression in dorsal root ganglion (DRG) macrophages. Deletion of Hk2 in myeloid cells, including both DRG macrophages and spinal microglia, led to the alleviation of mechanical pain during the first week after injury, along with attenuated microgliosis in the ipsilateral SDH, macrophage proliferation in DRGs, and suppressed inflammatory responses in DRGs. These data suggest that HK2 plays an important role in regulating neuropathic pain-related immune cell responses at acute phase and that HK2 contributes to neuropathic pain onset primarily through peripheral monocytes and DRG macrophages rather than spinal microglia.

Postoperative delirium prediction after cardiac surgery using machine learning models.

OBJECTIVE: Postoperative delirium (POD) is a common postoperative complication in elderly patients, especially those undergoing cardiac surgery, which seriously affects the short- and long-term prognosis of patients. Early identification of risk factors for the development of POD can help improve the perioperative management of surgical patients. In the present study, five machine learning models were developed to predict patients at high risk of delirium after cardiac surgery and their performance was compared. METHODS: A total of 367 patients who underwent cardiac surgery were retrospectively included in this study. Using single-factor analysis, 21 risk factors for POD were selected for inclusion in machine learning. The dataset was divided using 10-fold cross-validation for model training and testing. Five machine learning models (random forest (RF), support vector machine (SVM), radial based kernel neural network (RBFNN), K-nearest neighbour (KNN), and Kernel ridge regression (KRR)) were compared using area under the receiver operating characteristic curve (AUC-ROC), accuracy (ACC), sensitivity (SN), specificity (SPE), and Matthews coefficient (MCC). RESULTS: Among 367 patients, 105 patients developed POD, the incidence of delirium was 28.6 %. Among the five ML models, RF had the best performance in ACC (87.99 %), SN (69.27 %), SPE (95.38 %), MCC (70.00 %) and AUC (0.9202), which was far superior to the other four models. CONCLUSION: Delirium is common in patients after cardiac surgery. This analysis confirms the importance of the computational ML models in predicting the occurrence of delirium after cardiac surgery, especially the outstanding performance of the RF model, which has practical clinical applications for early identification of patients at risk of developing POD.

STK4 is a prognostic biomarker correlated with immune infiltrates in clear cell renal cell carcinoma.

BACKGROUND: Mammalian STE20-like kinase 1 (MST1/STK4/KRS2) is a highly conserved serine/threonine kinase and a central member of the Hippo signaling pathway. STK4 has been reported to play important roles in various tumors, but a systematic and comprehensive study of its function in clear cell renal cell carcinoma (ccRCC) has not been conducted. METHODS: In this study, we used immunohistochemistry (IHC), western blot (WB), quantitative real-time PCR (qPCR) experiments, and bioinformatics analysis to comprehensively analyze the expression, prognostic value, and immune infiltration of STK4 in ccRCC. RESULTS: Analysis of the TCGA database showed that the expression level of the STK4 gene in ccRCC patients depended on tumor stage, grade, and distant lymphatic metastasis. This was further confirmed by the results of IHC, WB, and qPCR. In addition, we used the receiver operating characteristic curve (ROC curve) to elucidate the diagnostic value of STK4 in ccRCC patients. According to the findings of the TIMER database, the high expression of STK4 is significantly associated with the survival of kidney cancer (including ccRCC) patients (p < 0.001), suggesting that STK4 is a reliable prognostic predictor. We then used gene set enrichment analysis (GSEA) to explore the mechanisms behind STK4 function in ccRCC. We found that STK4 may play a role in immune regulation interactions. Subsequently, we performed immune infiltration analysis of STK4. The results showed that STK4 may regulate the development of ccRCC by affecting the immune infiltration of NK and pDC cells. CONCLUSIONS: STK4 may be a prognostic marker for ccRCC and may help identify new strategies for treating ccRCC patients.

Compact multi-channel radio frequency pulse-sequence generator with fast-switching capability for cold-atom interferometers.

Cold-atom interferometers have matured into a powerful tool for fundamental physics research, and they are currently moving from realizations in the laboratory to applications in the field. A radio frequency (RF) generator is an indispensable component of these devices for controlling lasers and manipulating atoms. In this work, we developed a compact RF generator for fast switching and sweeping the frequencies and amplitudes of atomic-interference pulse sequences. In this generator, multi-channel RF signals are generated using a field-programmable gate array (FPGA) to control eight direct digital synthesizers (DDSs). We further propose and demonstrate a method for pre-loading the parameters of all the RF pulse sequences to the DDS registers before their execution, which eliminates the need for data transfer between the FPGA and DDSs to change RF signals. This sharply decreases the frequency-switching time when the pulse sequences are running. Performance characterization showed that the generated RF signals achieve a 100 ns frequency-switching time and a 40 dB harmonic-rejection ratio. The generated RF pulse sequences were applied to a cold-atom-interferometer gyroscope, and the contrast of atomic interference fringes was found to reach 38%. This compact multi-channel generator with fast frequency/amplitude switching and/or sweeping capability will be beneficial for applications in field-portable atom interferometers.

A clinical study on the surgical treatment of simple multiple rib fractures in older adult patients.

Background: The treatment of simple rib fractures in older adults can be divided into surgical treatment and nonsurgical treatment, with indications for surgery presently being unclear. This study was conducted to determine whether older adult individuals with simple multiple rib fractures can benefit from surgical treatment. Methods: A single-center, retrospective study was conducted. All 880 registry-identified patients aged ≥60 years who were admitted to Beijing Jishuitan Hospital with blunt rib fractures between 2013 to 2020 were included. They were divided into 2 groups according to whether internal fixation was performed. After screening of inclusion and exclusion criteria and propensity score matching, there were 226 patients, 113 of whom were placed in the operation group and 113 in the nonoperation group. The demographic characteristics, underlying diseases, number of rib fractures, hospital stay, intensive care unit (ICU) hospital stay, mechanical ventilation duration, fracture comorbidities on admission, pain index, and fracture healing condition were analyzed using chi-squared test and independent samples t test. Results: The pain score and fracture healing time were significantly improved in the operation group (P<0.05), while the duration of painkiller use was significantly shorter in the operation group (P=0.009). However, there was no significant differences in mortality, the incidence of bone nonunion, length of stay in the ICU, or duration of mechanical ventilation between the 2 groups. Conclusions: For patients in the clinical study, internal fixation surgery could reduce fracture healing time and minimize the use of painkillers. Surgical treatment was determined to be safe, as it did not increase the mortality of the older adult patients. For older patients with simple rib fractures who have no contraindications to surgery, internal fixation surgery is recommended.

L-lysine moderates thermal aggregation of coconut proteins induced by thermal treatment.

This work attempts to investigate the inhibitory effect of L-lysine (Lys) on the thermal aggregation of coconut protein (CP). The results showed that under neutral conditions (pH = 7), temperature reduced the solubility and enhanced the thermally induced gel formation of CP. In addition, Lys reduced the fluorescence properties, particle size and increased the turbidity of CP, which had an inhibitory effect on heat induced gels. The results indicate that Lys plays an important role in inhibiting protein thermal aggregation by interacting with CP to create steric hindrance and increase protein electrostatic repulsion.

Longitudinal high-dimensional analysis identifies immune features associating with response to anti-PD-1 immunotherapy.

Response to immunotherapy widely varies among cancer patients and identification of parameters associating with favourable outcome is of great interest. Here we show longitudinal monitoring of peripheral blood samples of non-small cell lung cancer (NSCLC) patients undergoing anti-PD1 therapy by high-dimensional cytometry by time of flight (CyTOF) and Meso Scale Discovery (MSD) multi-cytokines measurements. We find that higher proportions of circulating CD8+ and of CD8+CD101hiTIM3+ (CCT T) subsets significantly correlate with poor clinical response to immune therapy. Consistently, CD8+ T cells and CCT T cell frequencies remain low in most responders during the entire multi-cycle treatment regimen; and higher killer cell lectin-like receptor subfamily G, member 1 (KLRG1) expression in CCT T cells at baseline associates with prolonged progression free survival. Upon in vitro stimulation, CCT T cells of responders produce significantly higher levels of cytokines, including IL-1ß, IL-2, IL-8, IL-22 and MCP-1, than of non-responders. Overall, our results provide insights into the longitudinal immunological landscape underpinning favourable response to immune checkpoint blockade therapy in lung cancer patients.

Detection of Single Cancer Cell Multidrug Resistance With Single Cell Bioanalyzer.

Objectives: Despite the development of various cancer treatment methods, chemotherapy remains the most common approach for treating cancer. The risk of tumors acquiring resistance to chemotherapy remains a significant hurdle to the successful treatment of various types of cancer. Therefore, overcoming or predicting multidrug resistance in clinical treatment is essential. The detection of circulating tumor cells (CTCs) is an important component of liquid biopsy and the diagnosis of cancer. This study aims to test the feasibility of single-cell bioanalyzer (SCB) and microfluidic chip technology in identifying patients with cancer resistant to chemotherapy and propose new methods to provide clinicians with new choices. Methods: In this study, we used rapidly isolated viable CTCs from the patient blood samples method combined with SCB technology and a novel microfluidic chip, to predict whether patients with cancer are resistant to chemotherapy. SCB and microfluidic chip were used to select single CTCs, and the accumulation of chemotherapy drug was fluorescently measured in real time on these cells in the absence and presence of permeability-glycoprotein inhibitors. Results: Initially, we successfully isolated viable CTCs from the blood samples of patients. Additionally, the present study accurately predicted the response of 4 lung cancer patients to chemotherapeutic drugs. In addition, the CTCs of 17 patients with breast cancer diagnosed at Zhuhai Hospital of Traditional Chinese and Western Medicine were assessed. The results indicated that 9 patients were sensitive to chemotherapeutic drugs, 8 patients were resistant to a certain degree, and only 1 was completely resistant to chemotherapy. Conclusion: The present study indicated that the SCB technology could be used as a prognostic assay to evaluate the CTCs response to available drugs and guide physicians to treatment options that are most likely to be effective.

MsNRAMP2 Enhances Tolerance to Iron Excess Stress in Nicotiana tabacum and MsMYB Binds to Its Promoter.

Iron(Fe) is a trace metal element necessary for plant growth, but excess iron is harmful to plants. Natural resistance-associated macrophage proteins (NRAMPs) are important for divalent metal transport in plants. In this study, we isolated the MsNRAMP2 (MN_547960) gene from alfalfa, the perennial legume forage. The expression of MsNRAMP2 is specifically induced by iron excess. Overexpression of MsNRAMP2 conferred transgenic tobacco tolerance to iron excess, while it conferred yeast sensitivity to excess iron. Together with the MsNRAMP2 gene, MsMYB (MN_547959) expression is induced by excess iron. Y1H indicated that the MsMYB protein could bind to the "CTGTTG" cis element of the MsNRAMP2 promoter. The results indicated that MsNRAMP2 has a function in iron transport and its expression might be regulated by MsMYB. The excess iron tolerance ability enhancement of MsNRAMP2 may be involved in iron transport, sequestration, or redistribution.

CERS4 predicts positive anti-PD-1 response and promotes immunomodulation through Rhob-mediated suppression of CD8+Tim3+ exhausted T cells in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is one of the main malignant tumors with high mortality and short survival time. Immunotherapy has become the standard treatment for advanced NSCLC, but it has the problems of drug resistance and low response rate. Therefore, obtaining effective biomarkers to predict and enhance immune checkpoint inhibitors (ICIs) efficacy in NSCLC is important. Sphingolipid metabolism is recently found to be closely involved in tumor immunotherapy. CERS4, an important sphingolipid metabolizing enzyme, is positively correlated with the efficacy of anti-PD-1 therapy for NSCLC. Upregulation of CERS4 expression could improve the efficacy of anti-PD-1 therapy for NSCLC. High expression of CERS4 could downregulate the expression of Rhob in tumor. Significantly, the ratio of CD4+/CD8+ T cell increased and the ratio of Tim-3+/CD8+ T cell decreased in spleen and peripheral blood cells. When Rhob was knocked out, the efficacy of PD-1 mAb treatment increased, and the frequency of Tim-3+ CD8+ T cell decreased. This finding further confirmed the role of sphingolipid metabolites in regulating the immunotherapeutic function of NSCLC. These metabolites may improve the efficacy of PD-1 mAb in NSCLC by regulating the CERS4/Rhob/Tim-3 axis. Overall, this study provided a potential and effective target for predicting and improving the efficacy of ICIs for NSCLC. It also provided a new perspective for the study on the mechanisms of ICIs resistance for NSCLC.

Basing on the machine learning model to analyse the coronary calcification score and the coronary flow reserve score to evaluate the degree of coronary artery stenosis.

AIM: To obtain the coronary artery calcium score (CACS) for each branch in coronary artery computed tomography angiography (CCTA) examination combined with the flow fraction reserve (FFR) of each branch in the coronary artery detected by CT and apply a machine learning model (ML) to analyse and predict the severity of coronary artery stenosis. METHODS: All patients who underwent coronary computed tomography angiography (CCTA) from January 2019 to April 2022 in the HOSPITAL (T.C.M) AFFILIATED TO SOUTHWEST MEDICAL UNIVERSITY) were retrospectively screened, and their sex, age, characteristics of lipid-containing lesions, coronary calcium score (CACS) and CT-FFR values were collected. Five machine learning models, random forest (RF), k-nearest neighbour algorithm (KNN), kernel logistic regression, support vector machine (SVM) and radial basis function neural network (RBFNN), were used as predictive models to evaluate the severity of coronary stenosis. RESULTS: Among the five machine learning models, the SVM model achieved the best prediction performance, and the prediction accuracy of mild stenosis was up to 90%. Second, age and male sex were important influencing factors of increasing CACS and decreasing CT-FFR. Moreover, the critical CACS value of myocardial ischemia >200.70 was calculated. CONCLUSION: Through computer machine learning model analysis, we prove the importance of CACS and FFR in predicting coronary stenosis, especially the prominent vector machine model, which promotes the application of artificial intelligence computer learning methods in the field of medical analysis.

Combinational study with network pharmacology, molecular docking and preliminary experiments on exploring common mechanisms underlying the effects of weijing decoction on various pulmonary diseases.

Objective: 'Homotherapy for heteropathy' is a theory by which different diseases with similar pathogenesis can be treated with one Chinese formula. We aimed to explore the key components and core targets of Weijing decoction (WJD) in treating various lung diseases, namely, pneumonia, chronic obstructive pulmonary disease (COPD), acute lung injury (ALI), pulmonary fibrosis, pulmonary tuberculosis and non-small cell lung cancer (NSCLC), via network pharmacology, molecular docking and some experiments. Significance: This is the first study on the mechanism of WJD in treating various lung diseases by 'homotherapy for heteropathy'. This study is helpful for the transformation of TCM formula and development of new drugs. Methods: Active components and therapeutic targets of WJD were obtained via TCMSP and UniProt databases. Targets of the six pulmonary diseases were harvested from the GeneCards TTD, DisGeNet, UniProt and OMIM databases. Drug-disease intersection targets, corresponding Venn diagrams, herb-component-target networks and protein-protein interaction networks were established. Furthermore, GO biological function and KEGG enrichment analysis were completed. Moreover, the binding activity between main compounds and core targets was measured through molecular docking. Finally, the xenograft NSCLC mouse model was established. Immune responses were evaluated by flow cytometry and mRNA expression levels of critical targets were measured by real-time PCR. Results: JUN, CASP3 and PTGS2 were the most critical targets in six pulmonary diseases. The active compounds beta-sitosterol, tricin and stigmasterol stably bound to many active sites on target proteins. WJD had extensive pharmacological regulation, involving pathways related to cancer, inflammation, infection, hypoxia, immunity and so on. Conclusions: Effects of WJD against various lung diseases involve lots of compounds, targets and pathways. These findings will facilitate further research as well as clinical application of WJD.

Fufang Shenhua tablet inhibits renal fibrosis by inhibiting PI3K/AKT.

BACKGROUND: Fufang Shenhua tablet (SHT), a traditional Chinese medicine compound, has been utilized in the clinical management of chronic kidney disease (CKD) for a long time. Nevertheless, the fundamental active constituents and potential mechanism of action remain unclear. Thus, the objective of this study was to investigate the renoprotective effect of SHT on residual renal tissue in CKD model rats and to explore its primary efficacious components and their underlying mechanism. METHODS: After a 12-week period of SHT treatment through gavage in a 5/6 nephrectomized animal model of CKD, we evaluated the body weight, renal function, and renal pathological changes. Furthermore, the expression levels of fibronectin (FN), collagen I (COL-1), α-smooth muscle actin (α-SMA), and vimentin in renal tissues were assessed. In addition, network pharmacology analysis and molecular docking were utilized to predict the primary active components, potential therapeutic targets, and intervention pathways through which SHT could potentially exert its anti-kidney fibrosis effects. Subsequently, these predictions were validated in renal tissues of rats with CKD and in transforming growth factor ß1 (TGF-ß1)-induced HK-2 cells. RESULTS: SHT significantly improved renal function and reduced renal pathological damage and fibrosis in CKD model rats. Network pharmacological analysis identified 62 active components in SHT, with quercetin ranked first, and 105 protein targets shared by SHT and CKD. Based on the protein‒protein interaction network (PPI) and the SHT-CKD-pathway network, AKT1, MYC, IL2, and VEGFA were identified as key targets. Furthermore, GO and KEGG pathway enrichment analyses indicated that the renoprotective effect of SHT on CKD was closely associated with the PI3K/AKT signaling pathway. Molecular docking results demonstrated that the main active components of SHT had a strong binding affinity to the hub genes. During experimental validation, SHT hindered the activity of the PI3K/AKT signaling pathway in the renal tissue of CKD model rats. Furthermore, activation of the PI3K/AKT signaling pathway was correlated with a modified fibrotic phenotype in rats with 5/6 nephrectomy-induced CKD and TGF-ß1-induced HK-2 cells. Conversely, SHT and quercetin curtailed the activation of the PI3K/AKT signaling pathway and inhibited the formation of renal fibrosis, thus indicating that the PI3K/AKT signaling pathway is the basis of the antifibrotic effects of SHT. Ultimately, administration of the PI3K/AKT agonist 740Y-P counteracted the fibrotic phenotype of TGF-ß1-induced HK-2 cells induced by SHT. CONCLUSIONS: In this investigation, we employed a fusion of systems pharmacology and in vivo and in vitro experiments to elucidate the mechanism of SHT's antifibrotic properties via obstruction of the PI3K/AKT signaling pathway. Additionally, we surmised that AKT may be the principal target of SHT for the management of CKD and that quercetin may be its efficacious component. We have thus identified SHT as a promising drug for the amelioration of renal fibrosis and the progression of CKD.

Evaluation of surgical outcomes in elderly patients with rib fractures: A single-centre propensity score matching study.

Background: Rib fractures are the most common injuries in chest trauma. Compared with younger patients, elderly patients with rib fracture have a higher incidence of complications and mortality. A retrospective study was conducted to investigate the effect of internal fixation compared with conservative treatment on the outcome of rib fracture in elderly patients. Material and methods: We used a 1:1 propensity score matching method to perform a retrospective analysis of 703 elderly patients with rib fractures treated in the Thoracic Surgery Department of Beijing Jishuitan Hospital between 2013 and 2020. After matching, the length of hospital stay, death, symptom relief and rib fracture healing were compared between the surgery and the control group. Results: The study included 121 patients receiving SSRF in the surgery group and 121 patients receiving conservative treatment in the control group. The length of hospital stay in the surgery group was significantly longer than that in the conservative group (11.39d vs. 9.48d, p = 0.000). After 9 months of follow-up, the fracture healing rate in the surgery group was significantly higher than that in the control group (96.67% vs. 88.89%, p = 0.020). The fracture healing time (p = 0.000), improvement in pain score (p = 0.000) and duration of pain medication use (p = 0.000) were also significantly better in the surgery group than in the control group. Conclusion: Compared with conservative treatment, surgical treatment can prolong hospital stay to some extent. However, it has the advantages of more rapid healing and lessened pain. For rib fractures in elderly individuals, surgical treatment is a safe and effective option under strict surgical indications and is recommended.

Coinfection with influenza virus and non-typeable Haemophilus influenzae aggregates inflammatory lung injury and alters gut microbiota in COPD mice.

Background: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is associated with high mortality rates. Viral and bacterial coinfection is the primary cause of AECOPD. How coinfection with these microbes influences host inflammatory response and the gut microbiota composition is not entirely understood. Methods: We developed a mouse model of AECOPD by cigarette smoke exposure and sequential infection with influenza H1N1 virus and non-typeable Haemophilus influenzae (NTHi). Viral and bacterial titer was determined using MDCK cells and chocolate agar plates, respectively. The levels of cytokines, adhesion molecules, and inflammatory cells in the lungs were measured using Bio-Plex and flow cytometry assays. Gut microbiota was analyzed using 16S rRNA gene sequencing. Correlations between cytokines and gut microbiota were determined using Spearman's rank correlation coefficient test. Results: Coinfection with H1N1 and NTHi resulted in more severe lung injury, higher mortality, declined lung function in COPD mice. H1N1 enhanced NTHi growth in the lungs, but NTHi had no effect on H1N1. In addition, coinfection increased the levels of cytokines and adhesion molecules, as well as immune cells including total and M1 macrophages, neutrophils, monocytes, NK cells, and CD4 + T cells. In contrast, alveolar macrophages were depleted. Furthermore, coinfection caused a decline in the diversity of gut bacteria. Muribaculaceae, Lactobacillus, Akkermansia, Lachnospiraceae, and Rikenella were further found to be negatively correlated with cytokine levels, whereas Bacteroides was positively correlated. Conclusion: Coinfection with H1N1 and NTHi causes a deterioration in COPD mice due to increased lung inflammation, which is correlated with dysbiosis of the gut microbiota.

Sinomenine hydrochloride bidirectionally inhibits progression of tumor and autoimmune diseases by regulating AMPK pathway.

BACKGROUND: Chronic diseases such as tumors and autoimmune disorders are closely linked to metabolism and immunity and require conflicting treatment methods. AMPK can regulate cell growth and inflammation through energy metabolism. Sinomenine is a compound extracted from the traditional Chinese herb sinomenium acutum (Thunb.) Rehd. et Wils. It has been used to treat NSCLC (non-small-cell lung cancer) and RA (rheumatoid arthritis) in some studies, but with limited understanding of its mechanisms. OBJECTIVE: This study aims to examine the inhibitory effect of sinomenine hydrochloride (SH) on NSCLC and RA and to understand the underlying joint mechanisms. RESULTS: The results indicate that SH has a cytotoxic effect specifically on tumor cells, but not on normal cells. SH was found to induce cell apoptosis by activating the AMPK-mTOR pathway. Additionally, in autoimmune disease cell models, SH was shown to reduce the growth of RA-FLS cells by inhibiting the phosphorylation of AMPK, while having no effect on normal macrophages. Moreover, in vivo studies also showed that SH could reduce the production of pro-inflammatory cytokines such as TNF-α, IL-1ß, and IL-6 and slow the development of adjuvant arthritis in rats. Furthermore, SH was found to significantly suppress tumor growth in a tumor xenograft experiment in mice. CONCLUSIONS: This study provides new insights into the treatment of tumors and autoimmune diseases by demonstrating that SH can selectively inhibit the growth of NSCLC cells and the progression of RA through activation of the AMPK pathway.