Bioinformatics analyses of infiltrating immune cell participation on pancreatic ductal adenocarcinoma progression and in vivo experiment of the therapeutic effect of Shuangshen granules.

ETHNOPHARMACOLOGICAL RELEVANCE: Shuangshen granules (SSG), a nationally patented Chinese medicinal formula, including Panax quinquefolium L., Panax notoginseng (Burkill) F. H. Chen, and Cordyceps sinensis (Berk.) Sacc., has demonstrated remarkable therapeutic effects on pancreatic cancer in clinical treatment for nearly 10 years. Previous pharmacological researches have found that its main components, including ginsenosides and cordycepin have anticancer or preventive effects on pancreatic ductal adenocarcinoma (PDAC), which may be associated with immune metabolism. However, the underlying pharmacological mechanism of SSG in the truncation effect of PDAC progression is still unclear. AIM OF THE STUDY: To comprehensively understand the infiltrating immune cells during the different stages of the PDAC development chain and search for immune-related biomarkers that could potentially serve as drug targets through bioinformatic analysis. Meanwhile, the truncation effect of SSG on PDAC progression was also investigated. MATERIALS AND METHODS: The gene expression profiles at different PDAC developmental stages, including normal pancreas, pancreatic intraepithelial neoplasia (PanIN), and PDAC, were retrieved from the GEO database. The GEO2R tool was used to identify differentially expressed genes among the three groups. Functional enrichment analysis was performed with the GSEA software and Metascape platform. The CIBERSORT algorithm evaluated immune cell infiltration in the three groups, and immune-related biomarkers were identified. Correlation analysis was employed to examine the association between immune cells and the biomarkers. One of these biomarkers was selected for immunohistochemistry validation in human samples. Lastly, the effectiveness of SSG against PDAC progression and the influence on the selected biomarker were validated in vivo. The underlying pharmacological mechanisms were also explored. RESULTS: One dataset was obtained, where the functional enrichment of DEGs primarily involved immune effector processes and cytokine production of immune cells. The differential immune cells reflected during the progression from PanIN to PDAC were B memory cells, monocytes, M2 macrophages, and activated dendritic cells. The upregulation of ACTA2 was closely associated with M2 macrophage regulation. The immunohistochemistry on human samples validated significant differences in ACTA2 expression levels as the PDAC progressed. Moreover, animal experiments revealed that the national patented drug SSG ameliorated the pathological changes, decreased the expression of ACTA2 and its functional protein α-smooth muscle actin during PDAC progression. The underlying pharmacological mechanism was related to the regulation of macrophage polarization and downregulation of TGF-ß/Smad signaling pathway. CONCLUSIONS: The immunosuppressive environment changes during the PDAC progression. ACTA2 is a potential immuned-target for drug prevention of PDAC, while SSG could be a promising drug candidate.

Ginseng-containing traditional medicine preparations in combination with fluoropyrimidine-based chemotherapy for advanced gastric cancer: A systematic review and meta-analysis.

BACKGROUND: Ginseng-containing traditional medicine preparations (G-TMPs) in combination with fluoropyrimidine-based chemotherapy (FBC) are well-known treatments for advanced gastric cancer (AGC), with a superior efficacy to FBC alone. However, evidence regarding their efficacy remains limited. The purpose of this meta-analysis is to evaluate the efficacy and safety of G-TMPs in combination with FBC for the treatment of AGC. METHODS: Eight electronic databases were searched for randomized controlled trials (RCTs) using G-TMPs with FBC for the treatment of AGC. The primary outcome included the tumor response, while the secondary outcomes included the quality of life (QoL), proportions of peripheral blood lymphocytes, adverse drug reactions (ADRs), and levels of cancer biomarkers. The quality of evidence for each outcome was assessed using GRADE profilers. RESULTS: A total of 1,960 participants were involved in the 26 RCTs included. Patients treated with FBC plus G-TMPs had better objective response (risk ratio [RR] = 1.23, 95% confidence interval [CI]: 1.13 to 1.35, p < 0.00001) and disease control (RR = 1.13, 95% CI: 1.08 to 1.19, p < 0.00001) rates than those treated with FBC alone. Additionally, the combination group had a better QoL, higher proportions of CD3+ T cells, CD4+ T cells, and natural killer cells, as well as a higher CD4+/CD8+ T-cell ratio. Furthermore, lower levels of CA19-9, CA72-4, and CEA were confirmed in the combination treatment group. In addition, G-TMPs reduced the incidence of ADRs during chemotherapy. CONCLUSION: In combination with FBC, G-TMPs can potentially enhance efficacy, reduce ADRs, and improve prognosis for patients with AGC. However, high-quality randomized studies remain warranted. SYSTEMATIC REVIEW REGISTRATION: PROSPERO Number: CRD42021264938.

Retrospective Clinical Study on Integrated Chinese and Western Medicine in Treatment of Limited-Stage Small Cell Lung Cancer.

OBJECTIVE: To investigate the efficacy of integrated Chinese and Western medicine extending the progression-free survival (PFS) and overall survival (OS) of limited-stage small cell lung cancer (LS-SCLC) patients after the first-line chemoradiotherapy. METHODS: The data of 67 LS-SCLC patients who received combined treatment of CM and Western medicine (WM) between January 2013 and May 2020 at the outpatient clinic of Guang'anmen Hospital were retrospectively analyzed. Thirty-six LS-SCLC patients who received only WM treatment was used as the WM control group. The medical data of the two groups were statistically analyzed. Survival analysis was performed using the product-limit method (Kaplan-Meier analysis). The median OS and PFS were calculated, and survival curves were compared by the Log rank test. The cumulative survival rates at 1, 2, and 5 years were estimated by the life table analysis. Stratified survival analysis was performed between patients with different CM administration time. RESULTS: The median PFS in the CM and WM combination treatment group and the WM group were 19 months (95% CI: 12.357-25.643) vs. 9 months (95% CI: 5.957-12.043), HR=0.43 (95% CI: 0.27-0.69, P<0.001), respectively. The median OS in the CM and WM combination group and the WM group were 34 months (95% CI could not be calculated) vs. 18.63 months (95% CI: 16.425-20.835), HR=0.40 (95% CI: 0.24-0.66, P<0.001), respectively. Similar results were obtained in the further stratified analysis of whether the duration of CM administration exceeded 18 and 24 months (P<0.001). CONCLUSION: The combination treatment of CM and WM with continuing oral administration of CM treatment after the first-line chemoradiotherapy for LS-SCLC patients produced better prognosis, lower risks of progression, and longer survival than the WM treatment alone. (Registration No. ChiCTR2200056616).

Immortal Time Bias-Corrected Effectiveness of Traditional Chinese Medicine in Non-Small Cell Lung Cancer (C-EVID): A Prospective Cohort Study.

Background: Relatively little is known about the effect of traditional Chinese medicine (TCM) on prognosis of non-small cell lung cancer (NSCLC). Methods: In this nationwide, multicenter, prospective, cohort study, eligible patients aged 18-75 years with radical resection, and histologically confirmed stage II-IIIA NSCLC were enrolled. All patients received 4 cycles of standard adjuvant chemotherapy. Patients who received Chinese herbal decoction and (or) oral Chinese patent medicine for a cumulative period of not less than 6 months were defined as TCM group, otherwise they were considered as control group. The primary endpoint was DFS calculated using the Kaplan-Meier method. A time-dependent Cox proportional hazards model was used to correct immortal time bias. The secondary endpoints included DFS in patients of different characteristics, and safety analyses. This study was registered with the Chinese Clinical Trial Registry (ChiCTR1800015776). Results: A total of 507 patients were included (230 patients in the TCM group; 277 patients in the control group). The median follow-up was 32.1 months. 101 (44%) in the TCM group and 186 (67%) in the control group had disease relapse. The median DFS was not reached in the TCM group and was 19.4 months (95% CI, 14.2 to 24.6) in the control group. The adjusted time-dependent HR was 0.61 (95% CI, 0.47 to 0.78), equalling to a 39% reduction in the risk of disease recurrence with TCM. the number needed to treat to prevent one patient from relapsing was 4.29 (95% CI, 3.15 to 6.73) at 5 years. Similar results were observed in most of subgroups. Patients had a significant improvement in white blood cell decrease, nausea, decreased appetite, diarrhea, pain, and fatigue in the TCM group. Conclusion: TCM may improves DFS and has a better tolerability profile in patients with stage II-IIIA NSCLC receiving standard chemotherapy after complete resection compared with those receiving standard chemotherapy alone. Further studies are warranted.

The Best Evidence for the Prevention and Management of Lower Extremity Deep Venous Thrombosis After Gynecological Malignant Tumor Surgery: A Systematic Review and Network Meta-Analysis.

Background: To search and obtain the relevant evidence of prevention and management of lower extremity deep venous thrombosis (DVT) after gynecological malignant tumor operation and to summarize the relevant evidence. Methods: We searched the JBI evidence summary, up to date, the national comprehensive cancer network of the United States, the guide library of the National Institute of clinical medicine of the United Kingdom, PubMed, the Chinese biomedical literature database, CNKI, Wanfang, and other relevant evidence on the prevention and management of DVT in patients with gynecological malignant tumors. It includes clinical practice guidelines, best practice information book, expert consensus, evidence summary, original research, etc. The retrieval time limit is from database establishment till August 20, 2021. Two researchers independently evaluated the literature quality, combined with professional judgment, and extracted the literature that met the standards. Results: Finally, 18 literatures were included, including eight guidelines, three evidence summaries, four systematic evaluations, two expert consensuses, and one best practice information volume. A total of 26 pieces of the best evidence on the prevention and management of postoperative venous thrombosis in gynecological malignant tumors were summarized. It includes risk assessment, drug prevention, mechanical prevention, management strategy, and health education. Conclusion: This study summarized the best evidence of risk, prevention, and health management of DVT in postoperative patients with gynecological malignant tumors to provide evidence-based basis for clinical nurses and to improve the nursing level.

Clinical Efficacy and Safety of Traditional Medicine Preparations Combined With Chemotherapy for Advanced Pancreatic Cancer: A Systematic Review and Meta-Analysis.

Background: Traditional medicine preparations (TMPs) combined with chemotherapy is widely used for patients with advanced pancreatic cancer (APC); however, its efficacy and safety are still unclear. The purpose of this meta-analysis was to evaluate the clinical efficacy and safety of TMPs combined with chemotherapy for the treatment of APC. Methods: A systematic search of eight electronic databases for randomized controlled trials (RCTs) was conducted from inception to October 15, 2021. Tumor response was identified as primary outcome, whereas quality of life (QoL), cancer biomarkers, and adverse drug reactions (ADRs) were identified as secondary outcomes. Quality of the evidence for each outcome was evaluated by GRADE profiler. Results: In total, 31 RCTs involving 1,989 individuals were included. This meta-analysis showed that TMPs combined with chemotherapy significantly improved the objective response rate (ORR) (RR=1.64, 95% CI [1.43 to 1.88], p <0.00001), disease control rate (DCR) (RR=1.29, 95% CI [1.21 to 1.38], p <0.00001), and QoL (continuous data: SMD=0.81, 95% CI [0.44 to 1.18], p <0.0001, dichotomous data: RR=1.44, 95% CI [1.22 to 1.70], p<0.0001), compared to those with chemotherapy alone. In addition, the combined treatment group also had lower levels of CA19-9 (SMD=-0.46, 95% CI [-0.90 to -0.02], p=0.04) and CEA (SMD=-0.55, 95% CI [-0.93 to -0.17], p=0.004). Moreover, TMPs reduced the ADRs during chemotherapy. Conclusion: This systematic review suggests that TMPs combined with chemotherapy might be a potential option to enhance therapeutic effects and reduce ADRs during the treatment of APC. However, more high-quality randomized controlled trials with more participants are needed. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=209825, identifier PROSPERO Number: CRD42021264938.

Evaluation of Efficacy and Safety for Kanglaite Injection in the Control of the Malignant Pleural Effusions via Thoracic Perfusion: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Kanglaite injection (KLTI) is a traditional Chinese medicine (TCM) preparation with anti-tumor activity, which has been used to treat malignant tumors in China. The purpose of this study was to evaluate the efficacy and safety of intrapleural infusion with KLTI in the treatment of malignant pleural effusion (MPE). Methods: Randomized controlled trials (RCTs) on the efficacy and safety of intrathoracic infusion with KLTI in the treatment of MPE were searched from the PubMed, EMBASE, the Cochrane Library, CNKI, VIP, Wanfang and CBM databases. The primary outcome was objective remission rate (ORR). Secondary outcomes included quality of life (QOL) and incidence of adverse events (AEs). The Stata15.1 software and RevMan5.3 software were used to calculate risk ratios (RR) at 95% confidence intervals (CI) and conduct the meta-analysis. Results: This meta-analysis included 20 RCTs, involving 1,291 patients. The ORR of intrapleural infusion with KLTI + chemotherapy drugs in the treatment of MPE was higher than that of chemotherapy alone (RR) 1.23; 95%CI; 1.11-1.36, I 2 = 0%, z = 3.876, p = 0.000]. When KLTI is combined with cisplatin or KLTI 200 ml is used in every time, it is more advantageous to improve ORR. Moreover, compared with intrapleural infusion of chemotherapy drugs alone, KLTI combined with chemotherapy drugs significantly improved the QOL of patients with MPE (RR 1.28; 95%CI; 1.70-1.53, I 2 = 0%, z = 2.70, p = 0.007). In addition, the participation of KLTI reduced the gastrointestinal reaction (RR 0.79; 95% CI; 0.66-0.96; I 2 = 0%, z = 2.37, p = 0.018) and renal damage (RR 0.468; 95% CI; 0.23-0.945, I 2 = 0%, z = 2.11, p = 0.035) caused by chemotherapy drugs, but did not increase other adverse reactions (p > 0.05). Conclusion: The efficacy and safety of traditional chemotherapy drugs plus KLTI was superior to traditional chemotherapy drugs alone via intrapleural injection in controlling MPE, which suggested that KLTI can be used to treat MPE. However, a more rigorous RCT should be designed and completed before it is widely recommended.

Efficacy and Safety of Astragalus-Containing Traditional Chinese Medicine Combined With Platinum-Based Chemotherapy in Advanced Gastric Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Astragalus-containing traditional Chinese medicine (TCM) is widely used as adjunctive treatment to platinum-based chemotherapy (PBC) in patients with advanced gastric cancer (AGC) in China. However, evidence regarding its efficacy remains limited. This study aimed to evaluate the efficacy and safety of Astragalus-containing TCM combined with PBC in AGC treatment. METHODS: We searched for literature (up to July 19, 2020) in eight electronic databases. The included studies were reviewed by two researchers. The main outcomes were the objective response rate (ORR), disease control rate (DCR), survival rate, quality of life (QOL), adverse drug reactions (ADRs), and peripheral blood lymphocyte levels. The effect estimate of interest was the risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CIs). Trial sequential analysis (TSA) was used to detect the robustness of the primary outcome and to calculate the required information size (RIS). Certainty of the evidence was assessed using the GRADE profiler. RESULTS: Results based on available literature showed that, compared with patients treated with PBC alone, those treated with Astragalus-containing TCM had a better ORR (RR: 1.24, 95% CI: 1.15-1.34, P < 0.00001), DCR (RR: 1.10, 95% CI: 1.06-1.14, P < 0.00001), 1-year survival rate (RR: 1.41, 95% CI: 1.09-1.82, P = 0.009), 2-year survival rate (RR: 3.13, 95% CI: 1.80-5.46, P < 0.0001), and QOL (RR: 2.03, 95% CI: 1.70-2.43, P < 0.00001 and MD: 12.39, 95% CI: 5.48-19.30, P = 0.0004); higher proportions of CD3+ T cells and CD3+ CD4+ T cells; higher ratio of CD4+/CD8+ T cells; nature killer cells; and lower incidence of ADRs. Subgroup analysis showed that both oral and injection administration of Astragalus-containing TCM increased tumor response. Whether treatment duration was ≥8 weeks or <8 weeks, Astragalus-containing TCM could increase tumor response in AGC patients. Furthermore, Astragalus-containing TCM combined with oxaliplatin-based chemotherapy could increase the ORR and DCR; when with cisplatin, it could only increase the ORR. CONCLUSION: Current low to moderate evidence revealed that Astragalus-containing TCM combined with PBC had better efficacy and less side effects in the treatment of AGC; however, more high-quality randomized studies are warranted. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, identifier CRD42020203486.

Nitrogen and phosphorus removal in simulated wastewater by two aquatic plants.

Water pollution control is the focus of environmental pollution control. Ecological water treatment is widely used because of its low cost and landscape effect, and has no pollution. Aquatic plants have attracted wide attention because of their low cost and high level of resource utilization. In order to study the effects of emergent and submerged plants on the removal of different concentrations of wastewater, and the effect of pollutants on plant growth, two common aquatic plants found in Northeast China (Iris ensata Thunb. and Potamogeton malaianus Miq.) were selected. Under static conditions, the removal efficiency of nitrogen and phosphorus in wastewater with different concentrations by two kinds of plants was studied. The results showed that the removal rate of total nitrogen (TN) in medium- and high-pollutant concentration water samples and total phosphorus (TP) in medium- and low-pollutant concentration water with I. ensata reached more than 75%. The removal rate of TN in the medium-pollutant concentration water with P. malaianus reached 71.4%, while the removal efficiency of TN and TP in the low-pollutant concentration water was higher than 80%. In the Nanhu Park Lake samples, I. ensata had the highest removal rates of TN (80.38%) and TP (85.62%). This study shows that both I. ensata and P. malaianus can be used as aquatic plants to restore the water quality of urban lakes. This research provides an important basis for the phytoremediation and treatment of urban domestic wastewater and urban surface water bodies in Northern China.

Effect of acupoint therapies on chemotherapy-induced nausea and vomiting: A systematic review protocol.

BACKGROUND: Patients suffering from chemotherapy-induced nausea and vomiting (CINV) might have negative adherence of treatment. Acupoint therapies, including acupuncture, acupressure, acupoints injection, massage, and moxibustion, are safe medical procedures with minimal side effects for CINV, but studies about overall safety and effectiveness of acupoint therapies have not been scientifically and methodically evaluated in recent years. Evaluating the overall safety and effectiveness of acupoint therapies in patients with CINV is the purpose of this review. METHODS AND ANALYSIS: Relevant randomized controlled trials (RCTSs) are being searched in the following electronic databases: PubMed, Cochrane Library, Web of Science, EMBASE, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP database), Wanfang Data Knowledge Service Platform, and Chinese Biomedical Literature Database (CBM). We will also attempt to obtain the unpublished academic data by contacting the colleague, professor, or Institute of Traditional Chinese Medicine. The RCTs of the acupoint therapies for CINV patients will be searched in the databases from inception to July 2019. The primary outcomes are defined as severity, duration and frequency of nausea or vomiting, or both. The secondary outcomes are defined as any adverse events and quality of life. Performing the meta-analysis by using RevMan version 5 software. Mean difference (MD) or standardized mean difference (SMD) will express the continuous variables, while relative risk (RR) will express the categorical variables. RESULTS: The results of this review will provide a high-quality synthesis to evaluate the effectiveness and safety of acupoint therapies for CINV. CONCLUSION: This review will provide evidence to estimate whether acupoint therapies are effective interventions for CINV. DISSEMINATION: Evidence whether acupoint therapies are effective interventions for CINV will be provided by this systematic review. This knowledge will recommend better acupoint therapies and selections of acupoints which might be helpful in treating CINV. The findings of this systematic review will be disseminated via various forms of presentation and publication of the data in a journal or electronic databases. PROSPERO REGISTRATION NUMBER: CRD42019125538.