Herbal medicine for the prevention of chemotherapy-induced nausea and vomiting in patients with advanced colorectal cancer: A prospective randomized controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Chinese herbal medicine is increasingly used as complementary therapy to manage nausea and vomiting in different cultures. One such herbal recipe is the Hezhong granules, which contain classical antiemetic formulations, and are commonly used to prevent chemotherapy-induced nausea and vomiting (CINV). Modern pharmacological studies have shown that the key components of Hezhong granules, including Pinellia ternata (Thunb.), Evodia rutaecarpa (Juss.), and Zingiber officinale exhibit significant antiemetic and antitumor properties. Despite this promising evidence, controlling CINV remains a significant challenge in cancer treatment. Moreover, there is a lack of scientifically designed clinical trials to validate the efficacy and safety of classical antiemetic formulas for CINV interventions. AIMS OF THE STUDY: To investigate the efficacy and safety of Hezhong granules in preventing CINV in patients with advanced colorectal cancer (CRC). METHODS: This study was conducted between October 2020 and February 2022 in 12 hospital wards in Southwest China. In this multicenter, randomized controlled trial, we enrolled patients with advanced CRC who received fluorouracil-based chemotherapy. The patients were randomly assigned in a 1:1 ratio to either the Hezhong granule group (receiving a 5-HT3-receptor antagonist, dexamethasone, and Hezhong granules) or the placebo group (receiving a 5-HT3-receptor antagonist, dexamethasone, and placebo) during the first and second courses of chemotherapy. A 5-day diary was provided to all patients. Acute and delayed CINV were defined as CINV occurring within 24 h or between 24 and 120 h after the start of treatment. The primary endpoints were complete response rate (CRR, defined as the proportion of patients without nausea/vomiting) and objective response rate (ORR, defined as the proportion of patients without nausea/vomiting plus mild nausea/vomiting) for both acute and delayed CINV. Secondary endpoints were the daily rates of CINV events and Functional Living Index-Emesis (FLIE). To identify the predictors of CINV, we conducted multivariate ordered logistic regression analysis. This study was registered with the Chinese Clinical Trial, number ChiCTR2100041643. RESULTS: A total of 120 participants were randomly assigned, of whom 112 (56/56) completed two cycles and were included in the full analysis. In the acute phase, there were minor improvements in the Hezhong granule group, but there were no significant differences in the CRRs for nausea and vomiting (mean difference:10.7 %, P = 0.318, 0.324), while the ORRs increased by approximately 17.5 % (mean difference:16.1 %, P = 0.051; 17.9 %, P = 0.037, respectively). In the delayed phase, significant improvements of approximately 20 % were observed in both the CRRs (mean difference:19.6 %, P = 0.053; 21.4 %, P = 0.035) and ORRs (mean difference:17.9 %, P = 0.037, 0.043) for nausea and vomiting. Additionally, the daily rate of CINV events showed a mean difference of 19 % (P < 0.05). According to FLIE scores, approximately 70 % of patients who received Hezhong granules reported an improvement in their quality of life, with CINV symptoms having"no impact on daily life (NIDL)". No serious adverse events were attributed to herbal medicine. CONCLUSIONS: Hezhong granules proved to be both effective and well-tolerated in preventing CINV in patients with advanced CRC, with notable benefits in preventing delayed CINV. These promising results set the stage for subsequent phase III clinical trials and experimental research on Hezhong Granules.

Effect of Chinese herbal medicine formula on progression-free survival among patients with metastatic colorectal cancer: Study protocol for a multi-center, double-blinded, randomized, placebo-controlled trial.

INTRODUCTION: Metastatic colorectal cancer (mCRC) causes high cancer-related morbidity and mortality worldwide. Although chemotherapy and targeted agents treatment improve median survival and 5-year survival rates, there is only one-third of patients who adhere to treatment protocol until the pause of disease progression. Hezhong granule is a traditional Chinese herbal formula used for mCRC, which has shown good potential in alleviating the adverse effects of chemotherapy, enhancing the effectiveness of chemotherapy, and improving the quality of life. Therefore, the purpose of the study is to further validate the clinical efficacy and safety of the Chinese herbal medicine formula named Hezhong (HZ) in combination with standard chemotherapy and cetuximab (CET) or bevacizumab (BV) for treating mCRC. METHODS: In this multi-center, randomized, double-blinded, placebo-controlled trial, 360 eligible mCRC patients who will be randomly assigned to Hezhong or placebo group with a 1: 1 ratio. Participants in the Hezhong group will receive standard chemotherapy and CET or BV plus Hezhong Granule until the pause of disease progression, death, the exhibition of intolerable toxicity, or up to 6 months, while the placebo group will treat with standard chemotherapy and CET or BV plus placebo. The primary endpoint is progression-free survival (PFS). The secondary endpoints are overall survival (OS), objective response rate (ORR), safety, quality of life years (QOL), and chemotherapy-induced nausea and vomiting (CINV). EXPECTED RESULTS: The expected results of this trial are to improve the PFS and QOL of patients with mCRC and provide evidence-based recommendations for the treatment of mCRC with traditional Chinese medicine in China. TRIAL REGISTRATION: The trial has been registered with the Chinese Clinical Trial Registry (ChiCTR). The trial registration number was ChiCTR2100041643.

Targeted Approaches to HER2-Low Breast Cancer: Current Practice and Future Directions.

HER2-low breast cancer (BC) has a poor prognosis, making the development of more suitable treatment an unmet clinical need. While chemotherapy is the main method of treatment for HER2-low BC, not all patients benefit from it. Antineoplastic therapy without chemotherapy has shown promise in clinical trials and is being explored further. As quantitative detection techniques become more advanced, they assist in better defining the expression level of HER2 and in guiding the development of targeted therapies, which include directly targeting HER2 receptors on the cell surface, targeting HER2-related intracellular signaling pathways and targeting the immune microenvironment. A new anti-HER2 antibody-drug conjugate called T-DM1 has been successfully tested and found to be highly effective in clinical trials. With this progress, it could eventually be transformed from a disease without a defined therapeutic target into a disease with a defined therapeutic molecular target. Furthermore, efforts are being made to compare the sequencing and combination of chemotherapy, endocrine therapy, and HER2-targeted therapy to improve prognosis to customize the subtype of HER2 low expression precision treatment regimens. In this review, we summarize the current and upcoming treatment strategies, to achieve accurate management of HER2-low BC.

Association between hypertension and prognosis of patients with COVID-19: A systematic review and meta-analysis.

BACKGROUND: To investigate the association between hypertension and clinical outcomes, including in-hospital mortality, intensive care unit (ICU) admission, and invasive ventilation in patients with coronavirus disease 2019 (COVID-19) pneumonia. METHODS: We implemented a systematic search of PubMed for articles that assessed clinical outcomes of hypertensive patients infected with SARS-CoV-2. The primary outcomes evaluated included: in-hospital mortality, ICU admission, and the use of invasive ventilation. RESULTS: A total of 18 studies were included, involving 13,293 patients and covering from January 25, 2020, to April 20, 2020. The relationship between hypertension and prognosis in COVID-19 patients was evaluated. Results showed that hypertension was a risk factor for in-hospital mortality in COVID-19 patients (RR: 2.20, 95% CI, 1.83-2.65, P < .001). Moreover, patients with hypertension were more likely to be admitted to ICU (RR: 1.86, 95% CI, 1.13-3.07, P = .001) and to use invasive ventilation (RR: 2.99, 95% CI, 1.73-5.17, P < .001). CONCLUSIONS: Among COVID-19 patients, those combined with hypertension had a significantly higher risk of in-hospital deaths, admission to ICU, and need for invasive ventilation.

Anti-inflammatory and anti-apoptotic effects of Shaoyao decoction on X-ray radiation-induced enteritis of C57BL/6 mice.

ETHNOPHARMACOLOGICAL RELEVANCE: As a typical heat-clearing prescription, Shaoyao decoction (SYD) has a robust function of clearing viscera heat for the treatment of several intestinal discomfort symptoms. Clinical evidence indicated that it had the potential to cure radiation enteritis. However, its underlying mechanisms remain unclear. AIM OF THE STUDY: The present study was designed to probe the protective effects and the involved mechanisms of SYD on X-ray radiation-induced enteritis of C57BL/6 mice. MATERIALS AND METHODS: X-ray irradiation were used to establish the radiation enteritis model. Forty-eight male C57BL/6 mice (20 ± 2 g) were randomly divided into six groups: the control group, model group, dexamethasone group (DEX, 0.12 mg/kg) and SYD groups (0.12, 0.24 and 0.36 g/mL), respectively. All mice (except the control group) were intragastrically administrated for a continuous 7 days. H&E and Masson staining were employed to evaluate the morphological and collagen fibers changes of the colon. ELISA was performed to assess the levels of MDA, SOD, COX, LPS, IL-6, IL-1ß and TNF-α in serum. Moreover, TUNEL fluorescence, western blot and qRT-PCR were used to detect the levels of apoptosis-related proteins and genes of Dclk-1, ATM, MRE-11, Bcl-2, Bax, Caspase-3, and Cyto-c. Furthermore, immunofluorescent staining was applied to detect the protein levels of p53 and Claudin-1 in colon. RESULTS: Treatment with SYD decreased the exfoliated and necrotic epithelial cells and prevent the proliferate from damaged fibrous tissue in the crypt layer of mucos. The levels of serum peroxidation and pro-inflammatory cytokines (MDA, COX, LPS, IL-6, IL-1ß and TNF-α) were obviously inhibited, while SOD sharply increased in serum after administration. Moreover, SYD can significantly ameliorate the apoptosis of colon cells, evidenced by the reduced positive expression of TUNEL staining. Meanwhile, the results of qRT-PCR and western blot demonstrated that SYD can dramatically stimulate the expression of genes and proteins Dclk-1, ATM and MRE-11, thus promoting the expression of mitochondrial pro-apoptotic proteins Bax, Caspase-3 and Cyto-c, while increasing the level of anti-apoptotic protein Bcl-2. Furthermore, immunofluorescence revealed that SYD can notably decreased the protein level of p53 while reverse the reduction of Claudin-1. CONCLUSIONS: These results indicated that radiation enteritis in C57BL/6 mice can be ameliorated by treatment with SYD. The potential protection mechanisms may be involved in ameliorating tissue fibrosis by decreasing inflammatory and apoptotic events.

aMAP Score as a Predictor for Long-Term Outcomes in Patients with HBV-Related Acute-on-Chronic Liver Failure.

BACKGROUND AND AIM: The long-term outcomes of patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) remain not well known. This study aimed to investigate whether aMAP score can predict re-hospitalization, hepatocellular carcinoma (HCC) occurrence and long-term mortality in patients with HBV-ACLF. METHODS: A total of 82 patients diagnosed with HBV-ACLF and survived over 6 months were enrolled. The median follow-up period was 105 (75.9, 134.1) months. The Cox proportional hazards or logistic regression analysis was used to determine independent risk factors. Cumulative incidence of HCC and survival rate were evaluated using Kaplan-Meier analysis. RESULTS: Multivariate analysis identified that the aMAP risk score was an independent predictor of re-hospitalization (odds ratio [OR] = 1.112, 95% confidence interval [CI]: 1.021-1.211, p = 0.015), hepatocellular carcinoma occurrence (hazards ratio [HR] = 2.277, 95% CI: 1.014-5.114, p = 0.046) and mortality (HR = 1.366, 95% CI: 1.040-1.794, p = 0.025). High-risk aMAP scores were associated with higher risk of HCC occurrence and mortality. CONCLUSION: A higher aMAP score was an independent risk predictor of re-hospitalization, HCC occurrence and mortality, respectively, in HBV-ACLF patients who survived over 6 months, which can be applicable for early risk stratification and clinical decision.

Nomogram based on neutrophil-to-platelet ratio to predict in-hospital mortality in infective endocarditis.

Aim: To develop a nomogram based on neutrophil-to-platelet ratio (NPR) to predict in-hospital mortality in infective endocarditis (IE) patients. Methods: We retrospectively analyzed 294 consecutive patients classified as survivors or nonsurvivors according to hospitalization outcome. Logistic regression analyses were performed to identify independent predictors for in-hospital mortality. A nomogram based on them was established and assessed by receiver operating characteristic (ROC) curve analysis. Results: Admission NPR (odds ratio [OR] = 1.095, 95% CI: 1.037-1.156), positive blood culture (OR = 9.220; 95% CI: 1.478-57.521) and left-sided endocarditis (OR = 5.099; 95% CI: 1.104-23.553) independently predicted in-hospital mortality in IE. The area under the ROC curve for the nomogram based on these predictors was 0.832. Conclusion: The nomogram based on NPR could be used for early risk stratification of IE patients.

Association Between Nutritional Risk Screening Score and Prognosis of Patients with Sepsis.

BACKGROUND: Malnutrition is one of the most critical factors affecting patients' risk of infection and length of stay, and it may affect the prognosis of patients with sepsis. There have been no studies that have applied nutritional risk screening tools to stratify patients with sepsis according to prognosis. METHODS: We retrospectively analyzed the clinical data of 425 adult sepsis inpatients who were grouped based on nutritional risk screening (NRS) score, including a nutrition score, disease severity score, and age score. Prognostic factors were analyzed using univariate and multivariate regression analyses. RESULTS: Of the enrolled patients, 174 had an NRS score of ≥3; these patients were older and had a longer hospitalization time but lower body mass index (BMI), albumin (ALB) than others. Univariate Cox regression analysis showed that age, ALB, C-reactive protein (CRP), and NRS score were significantly (P<0.05) associated with in-hospital mortality. Multivariate analysis showed that age (hazard ratio [HR]=1.020, 95% confidence interval [CI]: 1.005-1.036; P=0.008) and ALB (HR=0.924, 95% CI: 0.885-0.966; P<0.001) were independent risk factors for sepsis-related mortality. The Kaplan-Meier analysis revealed that the cumulative in-hospital mortality of sepsis patients with an NRS score of ≥3 was significantly higher than that of patients with an NRS score of <3 (P=0.022). CONCLUSION: NRS scores can effectively risk stratify sepsis patients. Patients with high NRS scores should be monitored more closely to halt further disease progression.

Combined procalcitonin and hemogram parameters contribute to early differential diagnosis of Gram-negative/Gram-positive bloodstream infections.

BACKGROUND: Hemogram parameters and procalcitonin (PCT) play auxiliary roles in the diagnosis and outcome of sepsis. However, it is not clear whether these indicators can quickly distinguish bacterial classification or guide the choice of empirical antibiotics. METHODS: We retrospectively enrolled 381 patients with bloodstream infections (BSI), divided into Gram-positive bloodstream infections (GP-BSI) and Gram-negative bloodstream infections (GN-BSI). Demographic parameters, hemogram parameters, and PCT were recorded and compared between the two groups. RESULTS: The mean platelet volume (MPV), platelet distribution width (PDW), and PCT in the GN-BSI group were significantly higher than those in the GP-BSI group, while the platelet count (PLT), plateletcrit, platelet count-to-white blood cell count ratio (PWR), platelet count-to-neutrophil count ratio (PNR), platelet count-to-PCT ratio (PLT/PCT), and mean platelet volume-to-PCT ratio (MPV/PCT) were significantly lower in the GN-BSI group. Multivariate stepwise logistic regression analysis revealed that the independent predictors of GN-BSI were MPV, PWR, and PCT. The areas under the curve (AUC) for this prediction model was 0.79, with sensitivity =0.75 and specificity =0.71. CONCLUSIONS: There were significant differences in terms of PCT, platelet parameters, and platelet-related index-PCT ratio between GN-BSI and GP-BSI. Combined PCT and hemogram parameters are more conducive to the early differential diagnosis of bacterial classification of BSI.

Primary Pleural Squamous Cell Carcinoma, Highly Positive PD-L1, Shows Marked Response to Camrelizumab: A Case Report.

Here, we reported the rare case of primary pleural squamous cell carcinoma (PPSCC) in a 71-year-old male patient. After chemo and targeted therapies, the patient showed continuous tumor progression and clinical deterioration. Fortunately, the patient had a high expression level of PD-L1 (80%) in the tumor tissues. Ultimately, the patient survived for additional 6 months with camrelizumab treatment. In summary, camrelizumab may be a good candidate for the treatment of PPSCC, especially in tumors with high PD-L1 expression.

Anlotinib exerts anti-cancer efficiency on lung cancer stem cells in vitro and in vivo through reducing NF-κB activity.

Anlotinib is a multi-target tyrosine kinase inhibitor. Previous studies confirmed that anlotinib exerts anti-cancer efficiency. However, the functional roles of anlotinib on cancer stem cells (CSCs) are yet to be elucidated. In this study, lung CSCs were isolated and identified in vitro, and mouse xenografts were established in vivo. MTT assays, tumour sphere formation assays, TdT-mediated dUTP nick-end labelling (TUNEL) staining, Annexin V-FITC/PI staining, immunofluorescence analysis and Western blot were performed to investigate the anti-cancer effects of anlotinib on lung CSCs. The results showed that anlotinib inhibits the growth of lung CSCs in vitro and in vivo. In addition, anlotinib induced apoptosis of these cells along with down-regulated expression level of Bcl-2 whereas up-regulated Bax and cleaved caspase-3 expression. It also sensitized lung CSCs to the cytotoxicity of cisplatin and paclitaxel; the tumour sphere formation and expression levels of multiple stemness-associated markers, such as ALDH1 and CD133, were also decreased. Furthermore, the underlying mechanism indicated that anlotinib reduces the phosphorylated levels of NF-κB p65 and IκB-α in lung CSCs. Taken together, these findings suggested that anlotinib exerts potent anti-cancer effects against lung CSCs through apoptotic induction and stemness phenotypic attenuation. The mechanism could be associated with the suppression of NF-κB activity.

Efficacy and safety of dexmedetomidine as an adjuvant to local wound infiltration anaesthesia: A meta-analysis with trial sequential analysis of 23 randomised controlled trials.

To further identify the real efficacy and safety of dexmedetomidine as an adjuvant to local wound infiltration anaesthesia, we conducted this meta-analysis. The systematic search strategy was performed using PubMed, Embase, Cochrane Library, and Chinese databases. As a result, a total of 23 RCTs (1445 patients) were included. Patients receiving dexmedetomidine combined with local anaesthetics had a lower rescue analgesia rate [risk ratio (RR): 0.48; 95% confidence interval (CI): 0.36-0.65] and lower rescue analgesic consumption [weighted mean difference (WMD): -10.80 mg; 95%CI: -13.28 to -8.31 mg] than patients receiving local anaesthetics alone. The dexmedetomidine-related adverse reactions included bradycardia (RR: 1.33; 95%CI: 0.32-5.56) and hypotension (RR: 3.00; 95%CI: 0.49-18.42). In addition, the time to first analgesic request (WMD: 296.16 minutes; 95%CI: 165.69 minutes ~ 426.63 minutes), incidence of postoperative nausea and vomiting (PONV) and pain scores at 4 hours postoperatively were also significantly lower in patients receiving dexmedetomidine combined with local anaesthetics. This meta-analysis demonstrated that the use of dexmedetomidine as an adjuvant to wound infiltration is effective for reducing the rescue analgesia rate, rescue analgesic consumption and PONV. In addition, limited evidence shows that dexmedetomidine can prolong postoperative analgesia for approximately 5 hours. Further investigations on dexmedetomidine-related adverse reactions and the dose-response effect of dexmedetomidine in wound infiltration are warranted.

Ginsenosides for the treatment of metabolic syndrome and cardiovascular diseases: Pharmacology and mechanisms.

Epidemiological studies showed that the metabolic syndromes (MetS) and cardiovascular diseases (CVDs) are responsible for a serious threat to human health worldwide. MetS is a syndromes characterized by fat metabolism disorder, obesity, diabetes, insulin resistance and other risk factors, which increases the risk of CVDs initiation and development. Although certain drugs play a role in lowering blood sugar and lipid, some side effects also occur. Considering the multiple pathogenesis, a great deal of natural products have been attempted to treat metabolic syndromes. Ginsenosides, as the active components isolated from Panax ginseng C.A.Mey, have been reported to have therapeutic effects on MetS and CVDs, of which pharmacological mechanisms were further studied as well. This review aims to systematically summarize current pharmacological effects of ginsenosides on MetS and CVDs, potential mechanisms and clinic trials, which will greatly contribute to the development of potential agents for related disease treatment.

Indirubin inhibits cell proliferation, migration, invasion and angiogenesis in tumor-derived endothelial cells.

PURPOSE: Hepatocellular carcinoma is one of the most predominant malignancies with high fatality rate and its incidence is rising at an alarming rate because of its resistance to radio- and chemotherapy. Indirubin is the major active anti-tumor ingredient of a traditional Chinese herbal medicine. The present study aimed to analyze the effects of indirubin on cell proliferation, migration, invasion, and angiogenesis of tumor-derived endothelial cells (Td-EC). METHODS: Td-EC were derived from human umbilical vein endothelial cells (HUVEC) by treating HUVEC with the conditioned medium of human liver cancer cell line HepG2. Cell proliferation, migration, invasion, and angiogenesis were assessed by MTT, wound healing, in vitro cell invasion, and in vitro tube formation assay. RESULTS: Td-EC were successfully obtained from HUVEC cultured with 50% culture supernatant from serum-starved HepG2 cells. Indirubin significantly inhibited Td-EC proliferation in a dose- and time-dependent manner. Indirubin also inhibited Td-EC migration, invasion, and angiogenesis. However, indirubin's effects were weaker on HUVEC than Td-EC. CONCLUSION: Indirubin significantly inhibited Td-EC proliferation, migration, invasion, and angiogenesis.