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Background: Knee osteoarthritis (OA) is considered a major public health issue causing chronic disability worldwide with the increasing number of aging people. In China and increasingly worldwide, many sufferers with knee OA are using complementary and alternative medicine including herbal drug, herbal patch, acupuncture and Tuina etc., to alleviate their symptoms. However, evidence gathered from systematic reviews or randomized controlled trials (RCT) has only validated acupuncture for the management of osteoarthritic pain. Moreover, such Traditional Chinese Medicine (TCM) methods above are commonly used in an integrative way. This trial is aimed to compare the efficacy of an individually integrated TCM approach in the management of knee OA with other single treatments as parallel randomized controls.Methods/design: Five teaching hospitals will participate in this randomized controlled trial. 500 participants, 100 in each hospital, will be randomly assigned to receive oral administration of a Chinese herbal drug (counter osteophytes capsule), topical use of a Chinese herbal patch (Fufnag Zijin patch), acupuncture, Tuina and the individually integrated TCM approach. The individually integrated TCM approach consists of basic treatment of oral counter osteophytes capsule, variable use of Tuina, acupuncture and a herbal patch based on the severity of the patient's symptoms. The interventions are given for a period of 4 weeks. The primary outcome measure is the self-reported total score using the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC). Secondary outcome measures include patient and investigator global assessment of response to treatment, patient and investigator global assessment of OA condition, WOMAC pain, stiffness, and physical function subscales, short-form 36 (SF-36) and TCM assessment of OA condition measured by syndromes questionnaire. Mixed models and sensitivity analysis will be used for the statistical analysis.Discussion: The trial is designed to test the hypothesis that an individually integrated TCM approach is more effective than four treatment modalities used separately. The major limitation of this study is lack of placebo control and of double blinding.Trial Registration: Chinese Cochrane Center ChiCTR-TRC-00000176. [ABSTRACT FROM AUTHOR]

Crude oil pollution can profoundly alter the nitrogen (N) cycle in the soil. Here, a 30-day incubation with 15 N tracer approach was performed to assess the impacts of crude oil concentrations (medium: 10,000 mg kg -1 ; heavy: 50,000 mg kg -1 ) on soil N cycling based on a numerical model. Results showed that crude oil pollution significantly increased the gross N-transformation rates, but the rates of oxidation of recalcitrant organic N, the immbolization of NO 3 - and the adsorption of NH 4 + changed differently as a function of hydrocarbon concentrations. There was no significant difference of the oxidation rate of recalcitrant organic N between the medium and heavy oil-contaminated soils (medium: 0.1149 mmol N kg -1 d -1 ; heavy: 0.1299 mmol N kg -1 d -1 ), but the rates of NO 3 - immobilization (0.1135 mmol N kg -1 d -1 ) and NH 4 + adsorption were the highest (0.1148 mmol N kg -1 d -1 ) in the moderately oil-contaminated soils than those in the heavy polluted soil (0.0849 mmol N kg -1 d -1 and 0.0034 mmol N kg -1 d -1 , respectively). The NO 3 - immobilization rate was 2.5-fold higher than its reduction rate, indicating that NO 3 - immobilization played a more important role during the process of NO 3 - transformation. Microbial community structure analysis indicated that phyla of Actinobacteria and Ascomycota respectively promoted the immobilization of NO 3 - to recalcitrant organic N and the reduction of NO 3 - to NH 4 + . The genus of Aspergillus was related to net NH 4 + production, and the genera of Penicillium and Acremonium were responsible for oxidation of recalcitrant organic N to NO 3 - ., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Apatinib, a VEGFR2 receptor tyrosine kinase inhibitor, showed survival benefits in Asian patients with heavily pretreated advanced gastric cancer. However, the adverse event (AEs) profile of apatinib has limited its use. Dosing schedules are used to alleviate toxicities despite no supportive evidence. This study aimed to analyze the toxicity and effectiveness of apatinib alone, especially with different dosing strategies in advanced gastric cancer patients under a real-world setting. Data from the subpopulation of patients who failed ≥2 chemotherapy regimens enrolled in the AHEAD-G202 trial were analyzed. The primary endpoint was safety. The secondary endpoints were overall survival (OS) and progression-free survival (PFS). Totally 120 patients were included into three groups by the initial daily doses: 43 (35.8%) patients in the low-dose (250 mg) group, 67 (55.8%) patients in the mid-dose (425 mg to 500 mg) group, and 10 (8.3%) patients in the high-dose (675 to 850 mg) group. Grade 3/4 treatment-emergent AEs were infrequent (<5%), with the most commonly reported grade 3/4 AEs being hand-foot syndrome (4.2%), hypertension (4.2%,), fatigue (4.2%), and difficulty in swallowing (4.2%) which gradually decreased among the high-, mid-, and low-dose groups. The median OS and PFS were 6.33 months (95% CI, 4.57-7.73) and 3.83 months (95% CI: 1.40-4.20), respectively and were comparable among the three doses groups. We found heavily pretreated advanced gastric cancer patients can tolerate and benefit from lower-doses of apatinib therapy. The lower initial daily dosing strategy represents an alternative approach for optimizing apatinib dosing in clinical practice., Competing Interests: None., (AJCR Copyright © 2020.)

Objective: Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. The pathophysiology core issue is that the body initiates a severe inflammatory reaction in response to the invasion of pathogenic microorganisms at the initial stage of disease. Subsequently, the body begins to fight inflammation in order to balance immunity status and eventually induces the immune paralysis or immunosuppressive state characterized by exhaustion of immune cell. Both in innate immunity and in acquired immunity, some co-suppressor molecules on the surface of immune cells play important roles in immunosuppression, such as, programmed death receptor-1 (PD-1), T cell immunoglobulin and mucin-containing protein-3 (TIM-3), cytotoxic T lymphocyte associated antigen-4 (CTLA-4), natural killer cell receptor 2B4 (CD244), B and T lymphocyte attenuator (BTLA) and NKG2A (CD94), et al. Blocking the interaction between these co-suppressor molecules and their ligands can significantly reverse the immunosuppressive state in septic animal models or patients. In order to provide a reference for the monitoring and treatment of sepsis immune dysfunction, this article mainly summarizes the new findings on the role of those co-suppressor molecules in sepsis immune dysfunction in recent years.

MicroRNAs (miRNAs) have been demonstrated to play a central role in the initiation and development in many types of cancers including colorectal carcinoma (CRC). The purpose of current study was to investigate the clinical significance of serum miR-140-5p in CRC. Real-time PCR was performed to compare the expression level of miR-140-5p in the serum samples from 63 CRC patients, 20 patients with adenomas and 20 healthy controls. Then the clinical significance of serum miR-140-5p was further determined. Serum miR-140-5p was downregulated in the serum samples derived from CRC patients compared to patients with adenomas patients and controls (P<0.01). In addition, its expression level was able to discriminate CRC from adenomas as well as healthy controls with high accuracy, and was also significantly associated with various clinicopathological parameters including TNM stage (P = 0.0013) and lymph node metastasis (P = 0.0323). Serum miR-140-5p was remarkably upregulated in the patients who received surgery (P<0.01). Patients with lower serum miR-140-5p expression suffered poorer 5-year overall survival (P = 0.0034). In conclusion, our study revealed that serum miR-140-5p might function as a tumor suppressor in CRC, which might serve as a novel prognostic biomarker and therapeutic target., Competing Interests: None., (IJCEP Copyright © 2017.)

Background: Gastric and colorectal cancers remain the major causes of cancer-related death. Although chemotherapy improves the prognosis of the patients with gastrointestinal cancers, some patients do not benefit from therapy and are exposed to the adverse effects. The polymorphisms in genes including GSTM1 and GSTT1 have been explored to predict therapeutic efficacy; however, the results were inconsistent and inconclusive., Materials and Methods: A systematic review and meta-analysis was performed by searching relevant studies about the association between the GSTM1 and GSTT1 polymorphisms and chemotherapy efficacy in gastrointestinal cancers in databases such as PubMed, EMBASE, Web of Science, Chinese National Knowledge Infrastructure, and Wanfang database up to January 10, 2016. Subgroup analyses were also performed according to ethnicity, cancer type, evaluation criteria, study type, chemotherapy type, and age., Results: A total of 19 articles containing 3,217 cases were finally included. Overall analysis suggested that no significance was found between overall toxicity, neurotoxicity, neutropenia, gastrointestinal toxicity, tumor response, and progression-free survival, and the polymorphisms in GSTM1 and GSTT1, while GSTM1 polymorphism associated with overall survival (OS; hazard ratio =1.213, 95% confidence interval =1.060-1.388, P=0.005). Subgroup analyses suggested that neurotoxicity was associated with GSTM1 polymorphism in the Asian population, neutropenia was associated with GSTM1 polymorphism in palliative chemotherapy and older patients (mean age >60 years), and tumor response was associated with GSTT1 polymorphism in gastric cancer and responders defined by complete and partial responses. Meanwhile, GSTM1 was associated with OS in Caucasians, Asians, those with colorectal cancer, and patients with mean age <60 years. GSTT1 polymorphism was also associated with OS in Caucasians and patients with mean age >60 years., Conclusion: The polymorphisms in GSTM1 and GSTT1 did not associate with the chemotherapy-related toxicity in gastrointestinal cancers, while GSTT1 polymorphism associated with OS, and further well-designed, larger-scale epidemiological studies are needed to validate our results.