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BackgroundMetabolic syndrome (MS) is a significant risk factor for cardiovascular and cerebrovascular diseases, primarily driven by insulin resistance (IR). Although the herbal compound Chaihu Shugan powder (CSP) has demonstrated the potential to improve IR in animal models of MS, its mechanism of action remains incompletely understood. Therefore, this study aimed to investigate the biological pathways through which CSP exerts its therapeutic effects on IR in MS using both in vitro and in vivo methods.MethodsThe primary metabolites of CSP aqueous extract and CSP-containing serum were measured by LC-MS/MS. A mouse model of MS-related IR was induced by a high-fat, high-fructose diet combined with chronic immobilization stress. The CSP’s therapeutic potential was evaluated through glucose and insulin tolerance tests and hepatic insulin signaling molecules (p-IRS-1, IRS-1, p-Akt, and Akt). The expression of lipid metabolism-related factors (FFA, DAG, LXRα, SREBP-1, FASN, and ACC) in the liver was also measured. Hepatocyte IR was modeled using high-glucose and high-insulin conditions, and CSP impact was evaluated using 2-NBDG uptake and insulin signaling molecule expression. The specific mechanism of CSP was explored using the LXRα agonist T0901317.ResultsThe MS-related IR model exhibited a decreased p-Akt/Akt ratio and increased fasting glucose, insulin, homeostatic model assessment of IR, and hepatic lipid metabolism factors. Treatment with CSP mitigated these effects. In the hepatocyte IR model, CSP-containing serum improved glucose uptake and modulated the expression of insulin signaling and lipid metabolism factors. Furthermore, T0901317 reversed the beneficial effects of CSP, indicating the role of LXRα in CSP’s therapeutic action.ConclusionThe CSP ameliorated IR in MS by restoring fatty acid metabolism through the regulation of the LXRα/SREBP-1 signaling pathway.

BackgroundThe effect of combining prone ventilation with traditional Chinese medicine on severe pneumonia remains unclear.ObjectiveTo evaluate the effect of Fu Zheng Jie Du Formula (FZJDF) combined with prone ventilation on clinical outcomes in patients with severe pneumonia.MethodsThis single-center retrospective cohort study included 188 severe pneumonia patients admitted to the ICU from January 2022 to December 2023. Patients were divided into an FZJD group (receiving FZJDF for 7 days plus prone ventilation) and a non-FZJD group (prone ventilation only). Propensity score matching (PSM) was performed to balance baseline characteristics. The primary outcome was the change in PaO2/FiO2 ratio after treatment. Secondary outcomes included 28-day mortality, duration of mechanical ventilation, length of ICU stay, PaCO2, lactic acid levels, APACHE II score, SOFA score, Chinese Medicine Score, inflammatory markers, and time to symptom resolution.ResultsAfter PSM, 32 patients were included in each group. Compared to the non-FZJD group, the FZJD group showed significantly higher PaO2/FiO2 ratios, lower PaCO2, and lower lactic acid levels after treatment (p < 0.05 for all). The FZJD group also had significantly lower APACHE II scores, SOFA scores, Chinese Medicine Scores, and levels of WBC, PCT, hs-CRP, and IL-6 (p < 0.05 for all). Time to symptom resolution, including duration of mechanical ventilation, length of ICU stay, time to fever resolution, time to cough resolution, and time to resolution of pulmonary rales, was significantly shorter in the FZJD group (p < 0.05 for all). There was no significant difference in 28-day mortality between the two groups.ConclusionFZJDF as an adjuvant therapy to prone ventilation can improve oxygenation and other clinical outcomes in severe pneumonia patients. Prospective studies are warranted to validate these findings.

BackgroundIschemic stroke is a serious and sudden cerebrovascular condition that significantly affects individual’s health and imposes a substantial economic burden on medical management. Despite its widespread use in China, there is still a lack of reliable evidence regarding the efficacy of Shenmai injection (SMI) in acute ischemic stroke (AIS). We aimed to comprehensively assess the effectiveness and safety of SMI in treating AIS through a systematic review and meta-analysis.MethodsRandomized controlled studies (RCTs) investigating the efficacy of SMI in treating AIS were searched for in eight databases from the inception of each database till January 2024. We utilized the ROB 2.0 to assess the risk of bias. A meta-analysis was conducted using Review Manager 5.4, while sensitivity analyses and publication bias assessments were conducted using Stata 16.1.ResultsA total of 17 studies involving 1,603 AIS patients were included in our meta-analysis. Our results showed that SMI plus conventional treatments (CTs) was more effective than CTs alone in improving the total effective rate (RR 1.22, 95% CI: 1.14 to 1.30, p < 0.00001), the Barthel index (BI) (MD 12.18, 95% CI: 10.30 to 14.06, p < 0.00001), and reducing the National Institute of Health Stroke Scale Score (NIHSS) score (MD -3.05, 95% CI: 3.85 to −2.24, p < 0.00001) and Modified Rankin Scale (mRS) (MD -0.68, 95% CI: 0.86 to-0.49, p < 0.00001). In addition, SMI combination therapy was better than CTs alone in decreasing the levels of IL-6, IL-18, and hs-CRP. SMI therapy also enhanced the cerebral hemorheology of patients by reducing levels of fibrinogen and plasma viscosity. However, there was no significant difference in the incidence of adverse events, including elevated transaminase, rash, nausea, bleeding, urticaria, headache, vomiting, chest tightness, and facial flushes. Moreover, no serious adverse effects or life-threatening events were reported.ConclusionOur study shows that combining SMI with CTs effectively enhances the neurological function of patients with acute cerebral infarction. However, our findings should be interpreted considering the significant heterogeneity and suboptimal quality of the analyzed trials.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024504675, Identifier PROSPERO, CRD42024504675

Background: Dexmedetomidine is recommended for sedation in patients on mechanical ventilation. Whether age or ICU types could alter mortality in invasive mechanically ventilated patients with sepsis receiving dexmedetomidine is unknown.Methods: We included patients with sepsis receiving invasive mechanical ventilation from the Medical Information Mart for Intensive Care IV database. The exposure was intravenous dexmedetomidine administration during ICU stay. The primary outcome was 28-day mortality. The secondary outcomes were the length of ICU stay and liberation from invasive mechanical ventilation. Propensity score matching (PSM) and Cox proportional hazards regression were used to adjust for confounders and investigate any association. Restricted cubic spline models were used to evaluate potential nonlinear associations.Results: The pre-matched and propensity score-matched cohorts included 5,871 and 2016 patients, respectively. In the PSM cohorts, dexmedetomidine exposure was related to lower 28-day mortality (186 [17.7%] vs. 319 [30.3%]; p < 0.001). Patients receiving dexmedetomidine, regardless of whether they were younger (≤65 years; hazard ratio [HR], 0.31; 95% confidence interval [CI], 0.23–0.42; p < 0.001) or elderly (>65 years; HR, 0.65; 95% CI, 0.52–0.83; p < 0.001), was associated with lower 28-day mortality (61 [10.3%] vs. 168 [28.2%] for younger; 125 [27.2%] vs. 152 [33.0%] for elderly). Patients receiving dexmedetomidine was also associated with lower 28-day mortality (53 [12.6%] vs. 113 [26.5%] for surgical intensive care unit [SICU]; 133 [21.0%] vs. 206 [32.9%] for non-SICU) regardless of whether the first admission to the SICU (HR, 0.36; 95% CI, 0.25–0.50; p < 0.001) or non-SICU (HR, 0.50; 95% CI, 0.40–0.62; p < 0.001). Moreover, both dose and duration of dexmedetomidine administration were related to lower 28-day mortality than no dexmedetomidine in younger patients (p < 0.001), but it not statistically significant in elderly patients.Conclusion: Dexmedetomidine was associated with lower 28-day mortality in critically ill patients with sepsis receiving invasive mechanical ventilation, regardless of whether patients were younger or elderly, the first admission to the SICU or non-SICU.

Introduction: Type 2 diabetes (T2D) is a multifactorial complex chronic disease with a high prevalence worldwide, and Type 2 diabetes patients with different comorbidities often present multiple phenotypes in the clinic. Thus, there is a pressing need to improve understanding of the complexity of the clinical Type 2 diabetes population to help identify more accurate disease subtypes for personalized treatment.Methods: Here, utilizing the traditional Chinese medicine (TCM) clinical electronic medical records (EMRs) of 2137 Type 2 diabetes inpatients, we followed a heterogeneous medical record network (HEMnet) framework to construct heterogeneous medical record networks by integrating the clinical features from the electronic medical records, molecular interaction networks and domain knowledge.Results: Of the 2137 Type 2 diabetes patients, 1347 were male (63.03%), and 790 were female (36.97%). Using the HEMnet method, we obtained eight non-overlapping patient subgroups. For example, in H3, Poria, Astragali Radix, Glycyrrhizae Radix et Rhizoma, Cinnamomi Ramulus, and Liriopes Radix were identified as significant botanical drugs. Cardiovascular diseases (CVDs) were found to be significant comorbidities. Furthermore, enrichment analysis showed that there were six overlapping pathways and eight overlapping Gene Ontology terms among the herbs, comorbidities, and Type 2 diabetes in H3.Discussion: Our results demonstrate that identification of the Type 2 diabetes subgroup based on the HEMnet method can provide important guidance for the clinical use of herbal prescriptions and that this method can be used for other complex diseases.

Background: Copper as phytonutrient has powerful activity against health diseases. A newly discovered mechanism of cell death that affects energy metabolism by copper (“cuproptosis”) can induce multiple cuproptosis-related genes. Hepatocellular carcinoma (HCC) is a poorly prognosed widespread cancer having danger of advanced metastasis. Therefore, earlier diagnosis followed by the specific targeted therapy are required for improved prognosis. The work herein constructed scoring system built on ten cuproptosis-related genes (CRGs) to predict progression of tumor and metastasis more accurately and test patient reaction toward immunotherapy.Methods: A comprehensive assessment of cuproptosis patterns in HCC samples from two databases and a real-world cohort was performed on ten CRGs, that were linked to immune cell infiltration signatures of TME (tumor microenvironment). Risk signatures were created for quantifying effect of cuproptosis on HCC, and the effects of related genes on cellular function of HCC were investigated, in addition to the effects of immunotherapy and targeted therapy drugs.Results: Two distinct cuproptosis-associated mutational patterns were identified, with distinct immune cell infiltration characteristics and survival likelihood. Studies have shown that assessment of cuproptosis-induced tumor mutational patterns can help predict tumor stage, phenotype, stromal activity, genetic diversity, and patient prognosis. High risk scores are characterized by lower survival and worse treatment with anti-PD-L1/CTAL4 immunotherapy and first-line targeted drugs. Cytological functional assays show that CDKN2A and GLS promote proliferation, migration and inhibit copper-dependent death of HCC cells.Conclusion: HCC patients with high-risk scores exhibit significant treatment disadvantage and survival rates. Cuproptosis plays a non-negligible role in the development of HCC. Quantifying cuproptosis-related designs of tumors will aid in phenotypic categorization, leading to efficient personalized and targeted therapeutics and precise prediction of prognosis and metastasis.

Introduction: In hepatocellular carcinoma (HCC), alternative splicing (AS) is related to tumor invasion and progression.Methods: We used HCC data from a public database to identify AS subtypes by unsupervised clustering. Through feature analysis of different splicing subtypes and acquisition of the differential alternative splicing events (DASEs) combined with enrichment analysis, the differences in several subtypes were explored, cell function studies have also demonstrated that it plays an important role in HCC.Results: Finally, in keeping with the differences between these subtypes, DASEs identified survival-related AS times, and were used to construct risk proportional regression models. AS was found to be useful for the classification of HCC subtypes, which changed the activity of tumor-related pathways through differential splicing effects, affected the tumor microenvironment, and participated in immune reprogramming.Conclusion: In this study, we described the clinical and molecular characteristics providing a new approach for the personalized treatment of HCC patients.

Background: Nonalcoholic fatty liver disease (NAFLD) is the most common metabolic disease and is intertwined with cardiovascular disorders and diabetes. Chaihu Shugan powder (CSP) is a traditional Chinese medicine with a significant therapeutic effect on metabolic diseases, such as NAFLD. However, its pharmacological mechanisms remain to be elucidated.Methods: The main compounds of CSP were measured using LC-MS/MS. A network pharmacology study was conducted on CSP. Its potential active ingredients were selected according to oral bioavailability, drug similarity indices, and phytochemical analysis. After obtaining the intersected genes between drug targets and disease-related targets, the component-disease-target network and protein-protein interaction analysis were visualized in Cytoscape. GO and KEGG enrichment analyses were performed using the Metascape database. Six-week-old male C57BL/6 mice fed a high-fat high-fructose diet for 16 weeks plus chronic immobilization stress for 2 weeks, an in vivo model, were administered CSP or saline intragastrically. Liver histology, triglyceride and cholesterol levels, ELISA, and RT-PCR were used to assess hepatic inflammation and steatosis. Immunohistochemistry and western blotting were performed to assess protein levels.Results: A total of 130 potential target genes in CSP that act on NAFLD were identified through network pharmacology assays, including tumor necrosis factor (TNF), interleukin-6 (IL6), interleukin-1β (IL-1β), and peroxisome proliferator-activated receptor γ (PPARG). KEGG enrichment analysis showed that the main pathways were involved in inflammatory pathways, such as the TNF and NF-κB signaling pathways, and metabolism-related pathways, such as the MAPK, HIF-1, FoxO, and AMPK signaling pathways. The results in vivo showed that CSP ameliorated liver inflammation and inhibited hepatic fatty acid synthesis in the hepatocyte steatosis model. More specifically, CSP therapy significantly inhibited the expression of tumor necrosis factor α (TNFα), accompanied by a decrease in TNF receptor 1 (TNFR1) and the ligand availability of TNFR1.Conclusion: Through the combination of network pharmacology and in vivo validation, this study elucidated the therapeutic effect of CSP on NAFLD, decreasing liver inflammation and inhibiting hepatic fatty acid synthesis. More specifically, the anti-inflammatory action of CSP was at least partially mediated by inhibiting the TNFα/TNFR1 signaling pathway.

The Wenshenyang recipe (WSYR) has the effect of treating infertility, but the mechanisms underlying this activity have not been fully elucidated. In this study, network pharmacology and RNA sequencing were combined, with database-based “dry” experiments and transcriptome analysis-based “wet” experiments used conjointly to analyse the mechanism of WSYR in the treatment of infertility. In the dry analysis, 43 active compounds in WSYR and 44 therapeutic targets were obtained through a database search, 15 infertility pathways were significantly enriched, and key targets, such as ESR1, TP53, AKT1, IL-6, and IL-10 were identified. Then the wet experiments were performed to detect the expression changes of the 412 genes from 15 infertility pathways identified by dry analysis. HK-2 cells were treated with the three herbs of WSYR and subjected to targeted RNA sequencing. Based on the results, 92 of the 412 genes in 15 infertility pathways were identified as DEGs. Additionally, key targets, such as ESR2, STAT1, STAT3, and IL6, were also identified in the wet experiments. RT-qPCR experiments further verified that WSYR played an anti-inflammatory role by upregulating IL-4 and IL-10 and Epimedium brevicornu Maxim (Yinyanghuo) showed broader effect than Drynaria fortunei (Kunze) J. Sm (Gusuibu) and Cistanche deserticola Y.C.Ma (Roucongrong). By screening compounds of WSYR using molecular docking models of ESR1 and ESR2, it was further found that xanthogalenol in Gusuibu, arachidonate in Roucongrong, and anhydroicaritin in Yinyanghuo had good affinity for estrogen receptors. These findings provide evidence for an estrogen-regulating role of the three herbs in WSYR.

Background: Stable angina is a common condition with high morbidity and mortality rates. It has been reported that combining oral Chinese patent medicines (OCPMs) and Western medicine (WM) could potentially achieve a better effect than WM alone. However, the optimal OCPMs for stable angina remain controversial and merit further empirical research.Methods: PubMed, Embase, Web of Science, Cochrane Library, Ovid-Medline, Clinical Trials.gov, China National Knowledge Infrastructure, Wanfang Database, Weipu Journal Database, and Chinese Biomedical Literature Database were all searched from inception to 13 March 2022. We employed Version 2 of the Cochrane risk-of-bias tool (ROB2) to assess the overall quality of the selected studies. We also used R 4.1.2 and STATA 14.0 software applications to perform network meta-analysis, followed by sensitivity and subgroup analysis.Results: A total of 179 randomized controlled trials with 16,789 patients were included. The selected trials were all assessed as some concerns. OCPMs combined with WM had a better treatment effect than WM alone. In terms of the effective clinical rate, a significant increase was detected for Qishen Yiqi dripping pill (QSYQ)+WM as compared with Shensong Yangxin capsule (SSYX)+WM, Shexiang Baoxin pill (SXBX)+WM, Tongxinluo capsule (TXL)+WM, Xuefu Zhuyu capsule (XFZY)+WM, Qiliqiangxin capsule (QLQX)+WM, Naoxintong capsule (NXT)+WM, Fufang Danshen dripping pill (FFDS)+WM, and Danlou tablet (DL)+WM. QSYQ + WM had the highest-ranking probability (98.12%). Regarding the effective rate in ECG, QSYQ + WM was superior to SXBX + WM, TXL + WM, DL + WM, FFDS + WM, and NXT + WM. QSYQ + WM ranked first (94.21%). In terms of weekly frequency of angina, QLQX + WM obtained a better effect than FFDS + WM, Kuanxiong aerosol (KXQW)+WM, NXT + WM, QLQX + WM, SSYX + WM, SXBX + WM, and TXL + WM. QLQX + WM ranked first (100.00%). Regarding the duration of an angina attack, KXQW + WM was superior to SSYX + WM; KXQW + WM ranked first (95.71%). Adverting to weekly nitroglycerin usage, TXL + WM had the highest-ranking probability (82.12%). Referring to cardiovascular event rate, DL + WM had the highest effect (73.94%). Additionally, SSYX + WM had the lowest rate of adverse drug reactions (1.14%).Conclusion: OCPMs combined with WM had a higher efficacy. QSYQ + WM, QLQX + WM, KXQW + WM, TXL + WM, DL + WM, SSYX + WM, and SXBX + WM merit further investigation. SXBX + WM is presumably the optimal treatment prescription for both clinically effective and cardiovascular event rates. Further high-quality empirical research is needed to confirm the current results.Systematic Review Registration: URL = https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=316534, CRD 42022316534

Background: Acute tonsillitis has high morbidity. Chinese herbal injections (CHIs) were reported to be useful in treating acute tonsillitis and might reduce the probability of antibiotic resistance. Nevertheless, the optimal strategy for combining CHIs with western medicine (WM) to treat acute tonsillitis remains unclear.Methods: We retrieved data from the following databases with retrieval time from inception to 11 January 2022: PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, Weipu Journal Database, and Chinese Biomedical Literature Database. Version 2 of the Cochrane risk-of-bias tool (ROB2) was used for evaluating the quality of the included studies. R 4.1.2, STATA 14.0, and Python 3.10.4 were employed for network meta-analysis, with 5-dimensional K-means cluster analysis, meta-regression analyses, sensitivity analyses, and subgroup analyses.Results: A total of 110 randomized controlled trials including 12,152 patients were included. All the studies were rated as “high risk” and “some concerns”. In terms of improving clinical effectiveness rate, Qingkailing injection + WM ranked ahead of other interventions (89.51%). Regarding reducing antipyretic time, Reduning injection + WM had the highest-ranking probability (68.48%). As for shortening sore throat relief time, Shuanghuanglian injection + WM ranked first (76.82%). Concerning shortening red and swollen tonsils relief time, Yanhuning injection + WM possessed the highest-ranking probability (89.17%). In terms of reducing tonsillar exudate relief time, Xuebijing injection + WM ranked ahead of the other interventions (94.82%). Additionally, the results of the cluster analysis suggested that Xuebijing injection + WM, Reduning injection + WM, and Yanhuning injection + WM were probably the best interventions. Furthermore, adverse drug reactions rate of Xuebijing injection + WM, Reduning injection + WM, Yanhuning injection + WM, Qingkailing injection + WM, and Shuanghuanglian injection + WM were individually 0.00%, 3.11%, 3.08%, 4.29%, and 4.62%.Conclusions: CHIs + WM have a better impact on patients with acute tonsillitis than WM alone. Xuebijing injection, Reduning injection, and Yanhuning injection might have potential advantages in treating the disease. Concerning adverse drug reactions, Xuebijing injection is presumably the optimal CHI. More high-quality studies are needed to further confirm our findings.Systematic Review Registration: CRD42022303243; URL= https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=303243

Background: Septic shock is associated with high morbidity and mortality. Studies have reported that Chinese herbal injections (CHIs) in combination with Western medicine (WM) were more favorable. However, the debate on optimal CHIs is ongoing. The objective of this study is to explore the comparative effectiveness of CHIs for septic shock.Methods: We retrieved data from the English and Chinese databases with retrieval time from database inception to 30 September 2021. Network meta-analysis was performed, with evaluation of methodological quality among the included studies and assessment of strength of evidence among the outcomes.Results: A total of 77 RCTs with 5,647 patients were included. All the studies were rated as some concerns. In terms of 28-days-mortality, Yiqifumai injection (YQFM)+WM, Shuxuetong injection (SXT)+WM, Xuebijing injection (XBJ)+WM, and Shenfu injection (SF)+WM were better than WM; YQFM + WM and SXT + WM were superior for Shenmai injection (SM)+WM; YQFM + WM was superior for SF + WM; YQFM + WM ranked first. Regarding ICU length of stay, SF + WM and XBJ + WM were better than WM; XBJ + WM was superior for SF + WM; XBJ + WM ranked first. Concerning hospital length of stay, Shenqifuzheng injection (SQFZ)+WM, Shengmai injection (SGM)+WM, and XBJ + WM had greater potential than WM and SF + WM; SQFZ + WM ranked first. As for SOFA score at 7-days, XBJ + WM and SF + WM were superior for WM; XBJ + WM was superior for SF + WM; XBJ + WM ranked first. Regarding procalcitonin level at 7-days, SF + WM, SM + WM, and Xiyanping injection (XYP)+WM were better than WM; XYP + WM was superior for SF + WM, SGM + WM, SM + WM, Danshen injection (DS)+WM, and XBJ + WM; XYP + WM ranked first. Concerning serum lactate level at 7-days, SF + WM and SM + WM were more effective than XBJ + WM and WM; SM + WM ranked first. The comparisons were rated as moderate (15.05%), low (40.86%), and very low quality (44.09%); the strength of evidence of ranking probability for hospital length of stay was low whereas the remaining outcomes were rated as very low.Conclusions: CHIs combined with WM might have higher efficacies for septic shock than WM alone. YQFM, XBJ, SQFZ, XYP, SM, SGM, and SF may be the potential optimal CHIs for septic shock. More and better evidence is needed to validate the conclusions.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?, identifier CRD42021282958.

Sevoflurane can induce memory impairment during clinical anesthesia; however, the underlying mechanisms are largely unknown. TASK-3 channels are one of the potential targets of sevoflurane. Accumulating evidence supports a negative role of intracranial theta rhythms (4–12 Hz) in memory formation. Here, we investigated whether TASK-3 channels contribute to sevoflurane-induced memory impairment by regulating hippocampal theta rhythms. In this study, the memory performance of mice was tested by contextual fear conditioning and inhibitory avoidance experiments. The hippocampal local field potentials (LFPs) were recorded from chronically implanted electrodes located in CA3 region. The results showed that sevoflurane concentration-dependently impaired the memory function of mice, as evidenced by the decreased time mice spent on freezing and reduced latencies for mice to enter the shock compartment. Our electrophysiological results revealed that sevoflurane also enhanced the spectral power of hippocampal LFPs (1–30 Hz), particularly in memory-related theta rhythms (4–12 Hz). These effects were mitigated by viral-mediated knockdown of TASK-3 channels in the hippocampal CA3 region. The knockdown of hippocampal TASK-3 channels significantly reduced the enhancing effect of sevoflurane on hippocampal theta rhythms and alleviated sevoflurane-induced memory impairment. Our data indicate that sevoflurane can increase hippocampal theta oscillations and impair memory function via TASK-3 channels.