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Objective: This study aims to investigate the impact of ultrasound-guided combined with water and air mixed injection method for nasal intestinal tube placement on gastrointestinal burden in patients with severe acute pancreatitis. Methods: A cohort of 116 patients with severe acute pancreatitis admitted to the hospital from August 2021 to July 2023 were included. They were randomly divided into the control group (58 cases, nasal intestinal tube placement using ultrasound-guided combined water injection) and the observation group (58 cases, nasal intestinal tube placement using ultrasound-guided combined with water and air mixed injection). The incubation time, volume of water injected during the incubation, nasal intestinal tube visualization rate, and success rate of one-time incubation were recorded for both groups. Gastrointestinal mucosal barrier function, Nutritional index level including intestinal fatty acid-binding protein (I-FABP), D-lactate and nutritional index levels including hemoglobin (Hb), serum albumin (ALB), retinol-binding protein (RBP) were compared between the two groups before tube placement and at 7 days after incubation. Complications in both groups were also recorded. Results: The incubation time in the observation group was shorter, and the volume of water injected during the incubation was lower than in the control group. The nasal intestinal tube visualization rate and success rate of one-time incubation were higher in the observation group (P < .05). At 7 days after incubation, the levels of I-FABP and D-lactate were lower in the observation group than in the control group (P < .05). At 7 days after incubation, The levels of I-FABP and D-lactate in the observation group were lower than those in the control group, Hb and RBP levels were higher in the observation group than in the control group (P < .05), while there was no significant difference in ALB levels between the two groups (P > .05). The incidence of complications was lower in the observation group than in the control group (P < .05). Conclusion: Ultrasound-guided combined with water and air mixed injection method for nasal intestinal tube placement in patients with severe acute pancreatitis can shorten the incubation time, reduce the volume of water injected during the incubation, improve the nasal intestinal tube visualization rate and success rate of one-time incubation, enhance gastrointestinal mucosal barrier function and nutritional index in patients, and reduce the incidence of complications.
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AIM: The aim of this clinical study was to explore the effects of thumb-tack needling combined with sporting (TTNS) therapy on the improvement of pain and joint function in older adult patients with knee osteoarthritis (KOA). METHODS: A total of 120 older adult patients with KOA were randomly assigned to receive TTNS therapy or medicine treatment (Med group) only for 1 month. The patients were followed up for 3 months and clinical efficacies were evaluated using a visual analog scale to assess pain, the Lequesne scoring system to assess motor function, and the Western Ontario and McMaster University Osteoarthritis Index to assess KOA severity. Blood was collected to measure the levels of interleukin-6 and tumor necrotic factor-alpha using enzyme-linked immunosorbent assay. RESULTS: The data suggested that TTNS therapy resulted in a significantly higher clinical efficacy (P = 0.012). Visual analog scale score, Lequesne index, and Western Ontario and McMaster University Osteoarthritis Index of the TTNS group at the time of post-treatment (1 month) and post-follow-up (3 months) were also lower compared with the Med group. Patients in the TTNS group also showed lower levels of serum tumor necrotic factor-alpha and interleukin-6. CONCLUSIONS: TTNS therapy is more efficacious than pharmacological treatment in improving the clinical outcomes of patients with KOA, which suggests its clinical utility in the management of KOA. Geriatr Gerontol Int 2024; 24: 415-420.
Subject(s)
Neoplasms , Osteoarthritis, Knee , Aged , Humans , Interleukin-6 , Osteoarthritis, Knee/therapy , Pain , Percutaneous Collagen Induction , Thumb , Treatment OutcomeABSTRACT
INTRODUCTION: Irinotecan is a novel first-line therapy for colorectal cancer, but the toxicity and side effects include diarrhea without satisfactory treatments. Chinese herbal decoction (CHD) is an effective complementary and alternative prevention and therapy for irinotecan induced diarrhea (IID). This systematic review and meta-analysis of randomized controlled trials (RCTs) aims to assess the preventive effect of CHD in the treatment of IID. METHODS: Seven databases (PubMed, COCHRANE, EMBASE, CNKI, VIP, Wanfang, and CBM) were screened for random controlled trials on the prevention and treatment of IID by CHD from January 1980 to May 2022. The Cochrane Collaboration Risk of Bias (ROB 2.0) was applied for bias risk assessment, and the Grading Recommendation Assessment, Development, and Evaluation (GRADE) for quality of evidence. Meta-analysis was conducted with RevMan 5.3 software. In addition, a subgroup analysis was conducted on different grades of diarrhea, the incidence and duration of diarrhea, the selection of specific Chinese herbal medicine decoction, and the incidence of adverse reactions. Risk ratios (RR) and 95% confidence intervals (CIs) were calculated for all data by combining the meta-analysis with fixed or random-effects models based on outcome heterogeneity. RESULTS: Fourteen RCTs involving 1056 participants were included. The study results displayed that the incidence of IID was lower with the use of CHD than the no-treatment group (RR = 0.55, 95% CI = 0.40-0.75, P = 0.0002). CHD in combination with western medicine (WM) was more effective than WM alone for IID (RR = 0.44, 95% CI 0.23-0.84, P = 0.01). This protective effect was more pronounced for severe grade III-V diarrhea (RR = 0.41, 95% CI = 0.26-0.64, P < 0.0001). In the specific Chinese herbal medicine decoction, the Banxia Xie Xin decoction presented better effectiveness (RR = 0.18, 95% CI: 0.05-0.63, P = 0.007) than WM alone. The Huangqin decoction was the most widely studied interventional scheme (n = 5). The relative risk (RR) of the Huangqin decoction was 0.56. No obvious adverse reactions were observed. CONCLUSION: This study demonstrated that CHD has a preventive effect on IID and could be used as a complementary therapy with few side effects. However, additional large-sample, high-quality, randomized, double-blind trials are needed to guide the clinical practice scientifically. SYSTEMATIC REVIEW REGISTRATION: www.crd.york.ac.uk/prospero (NO: CRD42020189506).
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Complementary Therapies , Drugs, Chinese Herbal , Medicine , Humans , Drugs, Chinese Herbal/therapeutic use , Irinotecan/adverse effects , Diarrhea/chemically induced , Diarrhea/drug therapy , Randomized Controlled Trials as TopicABSTRACT
Background: Tai Chi Chuan (TCC) may have a positive impact on physical and psychological well-being in breast cancer patients, but the evidence remains limited and inconclusive. This systematic review aims to evaluate the effects of TCC on the quality of life (QoL) and psychological symptoms in women patients with breast cancer. Methods: This review has been registered on PROSPERO (ID: CRD42019141977). Randomized controlled trials (RCTs) of TCC for breast cancer were searched from eight major English and Chinese databases. All trials included were analyzed in accordance with the Cochrane Handbook. The primary outcomes were QoL, anxiety, and depression in patients with breast cancer. Fatigue, sleep quality, cognitive function, and inflammatory cytokine were the secondary outcomes. Results: Fifteen RCTs involving a total of 1,156 breast cancer participants were included in this review. The methodological quality of included trials was generally poor. The pooled results suggested that TCC-based exercise could significantly improve QoL [standardized mean difference (SMD)=0.35, 95%CI: 0.15-0.55, I 2 = 0, model: fixed, IV], anxiety [weighted mean difference (WMD)=-4.25, 95%CI: -5.88 to -2.63, I 2 = 0, model: fixed, IV], and fatigue (SMD=-0.87, 95%CI: -1.50 to -0.24, I 2 = 80.9%, model: random, DL) compared other controls, with moderate to low certainty of evidence. The improvement of QoL and fatigue by TCC was also clinically meaningful. However, TCC-based exercise failed to show any between-group differences in depression, sleep quality, cognitive function, and inflammatory cytokine. Post-hoc analysis revealed that TCC-based exercise outperformed the other exercise in improving shoulder function with very low certainty of evidence. Conclusion: Our findings manifested that TCC-based exercise is helpful for improving the QoL, anxiety, and fatigue in patients with breast cancer within the range of comparisons covered in this study. However, the results must be treated with great caution because of the methodological flaws of included trials. Larger, well-designed, and conducted randomized controlled trials with longer follow-up is warranted in the future to evaluate the important outcomes of TCC for breast cancer. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42019141977, identifier, CRD42019141977.
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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.
Subject(s)
Colorectal Neoplasms , Drugs, Chinese Herbal , Rectal Neoplasms , Humans , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bevacizumab/therapeutic use , Cetuximab/therapeutic use , Colorectal Neoplasms/pathology , Disease Progression , Multicenter Studies as Topic , Plant Extracts/therapeutic use , Progression-Free Survival , Quality of Life , Randomized Controlled Trials as Topic , Rectal Neoplasms/drug therapy , Treatment Outcome , Drugs, Chinese Herbal/therapeutic useABSTRACT
Hederagenin, a natural compound distributed in many medicinal plants, has a variety of pharmacological properties including anti-bacteria, anti-inflammation, anti-oxidation, and anti- apoptosis.. The aim of this study was to evaluate the effects of hederagenin on decreasing blood lipid and anti-oxidative stress in oleic acid-induced HepG2 cells and hyperlipidemic rats, and explore underlying mechanisms. In vitro, TG was used as the index to verify the lipid-lowering effect of hederagenin in oleic acid-induced HepG2 cells. In vivo, TC, TG, LDL-C, and HDL-C were used as direct indicators to study the antilipemic effect of hederagenin in hyperlipidemic rats. MDA, SOD, and GSH-PX were measured to analyze the anti-oxidative effect of hederagenin. The signaling pathways of anti-oxidation were evaluated using Western blot. Our results showed that hederagenin (250µmol/L) increased significantly TG clearance rate. In addition, treatment with hederagenin, XZK and simvastatin reduced effectively TC, TG, LDL-C and MDA content, and increased HDL-C, SOD and GSH-PX in HFD rats. Moreover, the phosphorylation level of p38 MAPK was inhibited after administration of hederagenin, XZK and simvastatin. Our results revealed that hederagenin possessed beneficial potentials for hypolipidemic effects, especially in TG clearance. The mechanism might be associated with inhibition of lipid absorption, reduction of lipid oxidation, and down-regulation of p38MAPK phosphorylation.
Subject(s)
Hypolipidemic Agents , Oleic Acid , Animals , Cholesterol, LDL , Hep G2 Cells , Humans , Hypolipidemic Agents/pharmacology , Hypolipidemic Agents/therapeutic use , Oleanolic Acid/analogs & derivatives , Rats , Simvastatin/pharmacology , Simvastatin/therapeutic use , Superoxide Dismutase , p38 Mitogen-Activated Protein KinasesABSTRACT
BACKGROUND: Since the declaration of COVID-19 as a global pandemic by the World Health Organization, countries are struggling with a shortage of medical capacities. It would be essential if the risk for preventable comorbidities, such as the common cold, can be reduced or prevented, so that the scarce medical resources and facilities can be focused on COVID-19. PURPOSE: To evaluate the effects of two herbal medicines (Jinhaoartemisia antipyretic granules and Huoxiangzhengqi oral liquids) in reducing the risk of the common cold in community-dwelling residents in China during the COVID-19 outbreak. STUDY DESIGN: A prospective open-label, parallel-group, cluster-randomized controlled trial (RCT), was conducted in Chengdu, China. METHODS: A total of 22,065 participants from 11 communities were recruited during a period of one month. The trial started on 30 January and participants were followed up till 29 February 2020. Participants were randomly assigned to receive either a five-day herbal medicine therapy plus a reference manual or a reference manual only if they were allocated to the control group. The primary endpoint was the occurrence of patient-reported common cold symptoms. The secondary endpoint was the time in days from the receipt of herbal drugs/reference manual and the occurrence of the common cold symptoms. RESULTS: Use of herbal medicine reduced the risk of the common cold by 89.6% (95% CI, 52.9% to 97.7%) in all community-dwelling residents, and by 94.0% (95% CI, 52.1% to 99.2%) in residents aged between 16 and 59 years old. Sensitivity analyses showed similar results. CONCLUSION: This community-based RCT found that the use of a herbal medicine therapy (Jinhaoartemisia antipyretic granules and Huoxiangzhengqi oral liquids) could significantly reduce the risks of the common cold among community-dwelling residents, suggesting that herbal medicine may be a useful approach for public health intervention to minimize preventable morbidity during COVID-19 outbreak.
Subject(s)
Common Cold/prevention & control , Drugs, Chinese Herbal/therapeutic use , Adolescent , Adult , COVID-19 , China , Female , Humans , Male , Middle Aged , Pandemics , Prospective Studies , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: Colorectal cancer (CRC) is a public health problem and the world's leading cancer killer. It is a disease with high incidence and mortality. Although chemotherapy has achieved some success in the treatment of CRC, drug resistance and tumor metastasis caused by chemotherapy are still the main causes of death in patients with CRC. Notably, many side effects associated with chemotherapy, such as nausea, vomiting, and peripheral neurotoxicity, are major challenges in the treatment of patients with CRC. Chinese herbal medicine (CHM) has been widely used as an adjunctive therapy for CRC, but its efficacy and safety are still uncertain. The aim of this systematic review is to assess the efficacy and safety of CHM for the treatment of CRC. METHODS: A comprehensive retrieval will be performed in the following electronic databases: PubMed, Cochrane Library, EMBASE, Web of Science, CNKI, SinoMed, VIP, and Wan Fang Data. The methodologic quality of randomized controlled trials will be assessed using the Cochrane risk assessment tool. Review Manager 5.3 software will be used for data synthesis and analysis. Funnel plot analysis and Egger test will be used to assess publication bias. The Grading of Recommendations Assessment, Development and Evaluation standard will be used to generate summary of finding table. RESULTS: The results of this systematic review will be used to summarize and evaluate the evidence from randomized controlled clinical trials of CHM as adjuvant therapy for CRC. CONCLUSION: This review will provide a detailed summary of the evidence to assess the efficacy and safety of CHM for CRC. OSF REGISTRATION: DOI 10.17605/OSF.IO/X2SKJ.
Subject(s)
Colorectal Neoplasms/drug therapy , Drugs, Chinese Herbal/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/mortality , Drug Therapy, Combination , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/adverse effects , Humans , Karnofsky Performance Status , Randomized Controlled Trials as Topic , Research Design , Survival AnalysisABSTRACT
The mismatch between maternal undernutrition and adequate nutrition after birth increases the risk of developing metabolic diseases. We aimed to investigate whether the hyperghrelinemia during maternal undernourishment rewires the hypothalamic development of the offspring and contributes to the conversion to an obese phenotype when fed a high-fat diet (HFD). Pregnant C57BL/6 J, wild type (WT) and ghrelin receptor (GHSR)-/- mice were assigned to either a normal nourished (NN) group, or an undernutrition (UN) (30% food restricted) group. All pups were fostered by NN Swiss mice. After weaning, pups were fed a normal diet, followed by a HFD from week 9. Plasma ghrelin levels peaked at postnatal day 15 (P15) in both C57BL/6 J UN and NN pups. Hypothalamic Ghsr mRNA expression was upregulated at P15 in UN pups compared to NN pups and inhibited agouti-related peptide (AgRP) projections. Adequate lactation increased body weight of UN WT but not of GHSR-/- pups compared to NN littermates. After weaning with a HFD, body weight and food intake was higher in WT UN pups but lower in GHSR-/- UN pups than in NN controls. The GHSR prevented a decrease in ambulatory activity and oxygen consumption in UN offspring during ad libitum feeding. Maternal undernutrition triggers developmental changes in the hypothalamus in utero which were further affected by adequate feeding after birth during the postnatal period by affecting GHSR signaling. The GHSR contributes to the hyperphagia and the increase in body weight when maternal undernutrition is followed by an obesity prone life environment.
Subject(s)
Hypothalamus/metabolism , Malnutrition/metabolism , Maternal Nutritional Physiological Phenomena , Obesity/metabolism , Receptors, Ghrelin/metabolism , Animals , Animals, Newborn , Diet, High-Fat/adverse effects , Female , Gene Deletion , Hypothalamus/growth & development , Male , Malnutrition/complications , Mice, Inbred C57BL , Obesity/etiology , Pregnancy , Receptors, Ghrelin/geneticsABSTRACT
To scientifically evaluate the intervention effect of Chinese medicine preventive administration(combined use of Huo-xiang Zhengqi Oral Liquid and Jinhao Jiere Granules) on community population in the case of coronavirus disease 2019(COVID-19), a large cohort, prospective, randomized, and parallel-controlled clinical study was conducted. Total 22 065 subjects were included and randomly divided into 2 groups. The non-intervention group was given health guidance only, while the traditional Chinese medicine(TCM) intervention group was given two coordinated TCM in addition to health guidance. The medical instructions were as follows. Huoxiang Zhengqi Oral Liquid: oral before meals, 10 mL/time, 2 times/day, a course of 5 days. Jinhao Jiere Granules: dissolve in boiling water and take after meals, 8 g/time, 2 times/day, a course of 5 days, followed up for 14 days, respectively. The study found that with the intake of medication, the incidence rate of TCM intervention group was basically maintained at a low and continuous stable level(0.01%-0.02%), while the non-intervention group showed an overall trend of continuous growth(0.02%-0.18%) from 3 to 14 days. No suspected or confirmed COVID-19 case occurred in either group. There were 2 cases of colds in the TCM intervention group and 26 cases in the non-intervention group. The incidence of colds in the TCM intervention group was significantly lower(P<0.05) than that in the non-intervention group. In the population of 16-60 years old, the incidence rate of non-intervention and intervention groups were 0.01% and 0.25%, respectively. The difference of colds incidence between the two groups was statistically significant(P<0.05). In the population older than 60 years old, they were 0.04% and 0.21%, respectively. The incidence of colds in the non-intervention group was higher than that in the intervention group, but not reaching statistical difference. The protection rate of TCM for the whole population was 91.8%, especially for the population of age 16-60(95.0%). It was suggested that TCM intervention(combined use of Huoxiang Zhengqi Oral Liquid and Jinhao Jiere Granules) could effectively protect community residents against respiratory diseases, such as colds, which was worthy of promotion in the community. In addition, in terms of safety, the incidence of adverse events and adverse reactions in the TCM intervention group was relatively low, which was basically consistent with the drug instructions.
Subject(s)
Betacoronavirus , Coronavirus Infections , Drugs, Chinese Herbal , Pandemics , Pneumonia, Viral , Adolescent , Adult , COVID-19 , Coronavirus Infections/drug therapy , Humans , Medicine, Chinese Traditional , Middle Aged , Pneumonia, Viral/drug therapy , Prospective Studies , SARS-CoV-2 , Young Adult , COVID-19 Drug TreatmentABSTRACT
Triptolide, a key ingredient from the traditional Chinese medicinal plant thunder god vine, which has been used to treat inflammation and autoimmune diseases for centuries, has been shown to be an irreversible inhibitor of the XPB subunit of the transcription factor TFIIH and initiation of RNA polymeraseâ II mediated transcription. The clinical development of triptolide over the past two decades has been limited by its toxicity and low water solubility. Herein, we report the development of a glucose conjugate of triptolide, named glutriptolide, which was intended to target tumor cells overexpressing glucose transporters selectively. Glutriptolide did not inhibit XPB activity inâ vitro but demonstrated significantly higher cytotoxicity against tumor cells over normal cells with greater water solubility than triptolide. Furthermore, it exhibited remarkable tumor control inâ vivo, which is likely due to sustained stepwise release of active triptolide within cancer cells. These findings indicate that glutriptolide may serve as a promising lead for developing a new mechanistic class of anticancer drugs.
Subject(s)
Antineoplastic Agents/administration & dosage , Antineoplastic Agents/therapeutic use , Diterpenes/administration & dosage , Diterpenes/therapeutic use , Drug Delivery Systems , Glucose/chemistry , Neoplasms/drug therapy , Phenanthrenes/administration & dosage , Phenanthrenes/therapeutic use , Animals , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Survival/drug effects , Diterpenes/chemistry , Epoxy Compounds/administration & dosage , Epoxy Compounds/chemistry , Epoxy Compounds/therapeutic use , HEK293 Cells , Humans , Mice , Phenanthrenes/chemistryABSTRACT
Objective To compare the conjoint effect of enteral nutrition (EN) and parenteral nutrition (PN) with single EN or PN on immune function, nutritional status, complications and clinical outcomes of patients with severe traumatic brain injury (STBI). Methods A prospective randomized control trial was carried out from January 2009 to May 2012 in Neurological Intensive Care Unit (NICU). Patients of STBI who met the enrolment criteria (Glasgow Coma Scale score 6~8; Nutritional Risk Screening ≥3) were randomly divided into 3 groups and were admi- nistrated EN, PN or EN+PN treatments respectively. The indexes of nutritional status, immune function, complications and clinical outcomes were examined and compared statistically. Results There were 120 patients enrolled in the study, with 40 pationts in each group. In EN+PN group, T lymthocyte subsets CD3+%, CD4+%, ratio of CD3+/CD25+, ratio of CD4+/CD8+, the plasma levels of IgA, IgM, and IgG at 20 days after nutritional treatment were significantly increased compared to the baseline(t=4.32-30.00, P<0.01), and they were significantly higher than those of PN group (t=2.44-14.70; P<0.05,or P<0.01) with exception of CD4+/CD8+, higher than those of EN group (t=2.49-13.31, P<0.05, or P<0.01) with exceptions of CD3+/CD25+, CD4+/CD8+, IgG and IgM. For the nutritional status, the serum total protein, albumin, prealbumin and hemoglobin were significantly higher in the EN (t=5.87-11.91; P<0.01) and EN+PN groups (t=6.12-13.12; P<0.01) than those in PN group after nutrition treatment. The serum prealbumin was higher in EN+PN group than that in EN group (t=2.08; P<0.05). Compared to the PN group, the complication occurrence rates of EN+PN group were significantly lower in stress ulcer (22.5% vs. 47.5%; χ2= 8.24, P<0.01), intracranial infection (12.5% vs 32.5%;χ2= 6.88, P<0.01) and pyemia (25.0% vs. 47.5%; χ2= 6.57, P<0.05). Compared to the EN group, the complication occurrence rates of EN+PN group were significantly lower in aspirated pneumonia (27.5% vs. 50.0%; χ2= 6.39, P<0.05), hypoproteinemia (17.5% vs. 55.0%; χ2= 18.26, P<0.01) and diarrhea (20.0% vs. 60.0%; χ2= 20.00, P<0.01). The EN+PN group also had significant less length of stay in NICU (t=2.51, 4.82; P<0.05, P<0.01), number of patients receiving assisted mechanical ventilation (χ2= 6.08, 12.88; P<0.05, P<0.01) and its durations (t=3.41, 9.08; P<0.05, P<0.01), and the death rate (χ2=7.50, 16.37; P<0.05, P<0.01) than those of EN or PN group. Conclusion Early EN+PN treatment could promote the recovery of the immune function, enhance nutritional status, decrease complications and improve the clinical outcomes in patients with severe traumatic brain injury.