OBJECTIVE: To observe the effect of transcutaneous electrical acupoint stimulation (TEAS) on postoperative pain in patients undergoing modified radical mastectomy for breast cancer. METHODS: A total of 140 female patients scheduled for unilateral modified radical mastectomy for breast cancer undergoing general anesthesia were randomized into a TEAS group (70 cases) and a sham TEAS group (70 cases, 2 cases dropped out). Patients in both groups received TEAS or sham TEAS at bilateral Neiguan (PC6), Zusanli (ST36), and Danzhong (CV17), respectively, from 30 min before anesthesia induction until the end of surgery, and on 1st, 2nd, and 3rd days after surgery for 30 min a time, once a day. On 1st, 2nd, and 3rd days after surgery, the pain visual analogue scale (VAS) score was observed; on 3, 6, 12 months after surgery, the incidence rate of chronic pain was observed; before surgery, and on 1st, 3rd, and 7th days after surgery, the serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10 were detected; the number of analgesia pump press, rescue analgesia, and the occurrence of adverse reaction after surgery were recorded in the two groups. RESULTS: In the TEAS group, the VAS scores on 1st and 2nd days after surgery, and the incidence rates of chronic pain on 3 and 6 months after surgery were lower than those in the sham TEAS group (P<0.05). On 1st, 3rd, and 7th days after surgery, the serum levels of TNF-α, IL-6, and IL-10 were increased compared with those before surgery in both groups (P<0.05, P<0.01); the above indexes in the TEAS group were lower than those in the sham TEAS group (P<0.05). The number of analgesia pump press and the incidence rate of rescue analgesia after surgery in the TEAS group were lower than those in the sham TEAS group (P<0.05). There was no statistically significant difference in the incidence of adverse reactions after surgery between the two groups (P>0.05). CONCLUSION TEAS can effectively improve both the postoperative acute pain and chronic pain in patients undergoing modified radical mastectomy for breast cancer, the mechanism may relate to inhibiting the inflammatory reaction.
Humans ; Female ; Acupuncture Points ; Pain, Postoperative/blood* ; Middle Aged ; Breast Neoplasms/surgery* ; Adult ; Transcutaneous Electric Nerve Stimulation ; Mastectomy, Modified Radical/adverse effects* ; Interleukin-6/blood* ; Tumor Necrosis Factor-alpha/blood* ; Interleukin-10/blood* ; Aged

OBJECTIVE: To observe the effect of perioperative transcutaneous electrical acupoint stimulation (TEAS) on postoperative fatigue syndrome (POFS) in elderly patients undergoing laparoscopic radical gastrectomy. METHODS: A total of 80 elderly patients scheduled for laparoscopic radical gastrectomy were randomized into a TEAS group and a sham TEAS group, 40 cases in each one. In the TEAS group, TEAS intervention was applied at bilateral Hegu (LI4), Neiguan (PC6), Zusanli (ST36) and Sanyinjiao (SP6) from 30 min before anesthesia induction until surgery completion, and at 18:00 on 1st, 2nd and 3rd days after surgery, once a day, 30 min a time. In the sham TEAS group, the same acupoints were selected and connected to the electroacupuncture device at the same time, without electrical stimulation. One day before surgery and 1, 3, 7 days after surgery, the 10-item short form of identity consequence fatigue scale (ICFS-10) score was observed, and the POFS incidence rate of 1, 3, 7 days after surgery was assessed in the two groups. One day before surgery, surgery completion, and 1, 3 days after surgery, the serum levels of superoxide dismutase (SOD), β-endorphin (β-EP) were detected; 1 day before surgery and 1, 3, 7 days after surgery, the serum level of tumor necrosis factor-α (TNF-α) was detected in the two groups. The pain visual analog scale (VAS) score was observed at 24, 48 and 72 h after surgery; the intraoperative dosage of propofol and remifentanil, and the incidence rate of postoperative nausea and vomiting, itching, respiratory depression were recorded in the two groups. RESULTS: In the TEAS group, on 1, 3, 7 days after surgery, except for the scores of item 8-10, the item scores and the total scores of ICFS-10 were lower than those in the sham TEAS group (P<0.001); on 3 and 7 days after surgery, the POFS incidence rates were lower than those in the sham TEAS group (P<0.05). In the TEAS group, on 1 and 3 days after surgery, the serum levels of SOD were higher than those in the sham TEAS group (P<0.05, P<0.01); at surgery completion, and on 1, 3 days after surgery, the serum levels of β-EP were higher than those in the sham TEAS group (P<0.001, P<0.01); on 1, 3, 7 days after surgery, the serum levels of TNF-α were lower than those in the sham TEAS group (P<0.01, P<0.001). In the TEAS group, at 24, 48 and 72 h after surgery, the pain VAS scores were lower than those in the sham TEAS group (P<0.001, P<0.01, P<0.05); the intraoperative dosage of remifentanil was lower than that in the sham TEAS group (P<0.001); the incidence rate of postoperative nausea and vomiting was lower than that in the sham TEAS group (P<0.01). CONCLUSION Perioperative TEAS intervention can effectively reduce the incidence rate of POFS, improve fatigue symptom and mental state in elderly patients undergoing laparoscopic radical gastrectomy, its mechanism may related to enhancing endogenous β-EP release, inhibiting inflammatory response, and reducing central oxidative stress, thereby promoting postoperative recovery.
Humans ; Acupuncture Points ; Male ; Female ; Aged ; Transcutaneous Electric Nerve Stimulation ; Postoperative Complications/therapy* ; Middle Aged ; Fatigue/etiology* ; Gastrectomy/adverse effects* ; beta-Endorphin/blood* ; Tumor Necrosis Factor-alpha/blood*

OBJECTIVE: To compare the clinical efficacy between thermo-electroacupuncture at yaosanzhen and oral celecoxib in the treatment of chronic lumbar muscle strain with cold dampness. METHODS: A total of 80 patients with chronic lumbar muscle strain of cold dampness were randomly divided into an observation group (40 cases, 1 case dropped out) and a control group (40 cases, 2 cases were excluded). The observation group was treated with thermo-electroacupuncture at yaosanzhen (bilateral Shenshu [BL23], Dachangshu [BL25], Weizhong [BL40]), disperse-dense wave was selected, with a pulse cycle of 0.08 s, current intensity of 1-3 mA, with needles heated to approximately 45 ℃, the duration was 25 min per session, once a day. The control group was given oral celecoxib capsules, once daily, 200 mg each time. Six sessions as one course, with a 1-day interval between courses, 2 courses were required in both groups. The TCM syndrome score, visual analogue scale (VAS) score, Oswestry disability index (ODI) score, and Japanese Orthopedic Association (JOA) score before and after treatment in both groups were compared. The serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), thromboxane B2 (TXB2) and C-reactive protein (CRP) were detected using ELISA method before and after treatment in both groups. The clinical efficacy was evaluated in both groups after treatment. RESULTS: After treatment, the TCM syndrome scores, VAS scores, ODI scores and serum levels of TNF-α, IL-6, TXB2, CRP in both groups were reduced compared with those before treatment (P<0.01), while the JOA scores were increased (P<0.01)；the TCM syndrome score, VAS score, ODI score and serum levels of TNF-α, IL-6, TXB2, CRP in the observation group were lower than those in the control group (P<0.01, P<0.05), and the JOA score was higher than that in the control group (P<0.01). The total effective rate of the observation group was 92.3% (36/39), which was superior to 78.9% (30/38) in the control group (P<0.05). CONCLUSION Thermo-electroacupuncture at yaosanzhen can alleviate pain symptom in patients with chronic lumbar muscle strain of cold dampness, regulate lumbar function, reduce the levels of inflammatory factors, and the therapeutic effect is superior to oral celecoxib.
Humans ; Male ; Female ; Middle Aged ; Adult ; Electroacupuncture ; Acupuncture Points ; Sprains and Strains/genetics* ; Cold Temperature ; Tumor Necrosis Factor-alpha/blood* ; Interleukin-6/blood* ; Aged ; Treatment Outcome ; Young Adult ; C-Reactive Protein/metabolism* ; Chronic Disease/therapy* ; Lumbosacral Region/physiopathology*

This study aims to investigate the antipyretic effects and mechanisms of ethanol extracts from Arisaematis Rhizoma fermented with bile from different sources on a rat model of fever induced by a dry-yeast suspension. The rat model of fever was established by subcutaneous injection of 20% dry-yeast suspension into the rat back. The levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6) in the serum, as well as prostaglandin E_2(PGE_2) and cyclic adenosine monophosphate(cAMP) in the hypothalamus, were determined by ELISA. Metabolomics analysis was then performed on serum and hypothalamus samples based on UPLC-Q-TOF MS to explore the potential biomarkers and metabolic pathways. The results showed that the body temperatures of rats significantly rose 4 h after modeling. After oral administration of high-dose ethanol extracts of Arisaematis Rhizoma fermented with bovine bile(NCH) and porcine bile(ZCH), the body temperatures of rats declined(P<0.05), and the NCH group showed better antipyretic effect than the ZCH group. Additionally, compared with the model group, the NCH and ZCH groups showed lowered levels of IL-1β, IL-6, TNF-α, PGE_2, and cAMP(P<0.01). The results of serum and hypothalamus metabolomics analysis indicated that both NCH and ZCH exerted antipyretic effects by regulating phenylalanine metabolism, sphingolipid metabolism, arachidonic acid metabolism, and steroid hormone biosynthesis. Collectively, both NCH and ZCH can play an obvious antipyretic role in the rat model of dry yeast-induced fever, and the underlying mechanism might be closely associated with inhibiting inflammation and regulating metabolic disorders. Moreover, NCH demonstrates better antipyretic effect.
Animals ; Rats ; Male ; Fermentation ; Rats, Sprague-Dawley ; Rhizome/metabolism* ; Drugs, Chinese Herbal/chemistry* ; Bile/chemistry* ; Antipyretics/chemistry* ; Fever/metabolism* ; Cattle ; Swine ; Tumor Necrosis Factor-alpha/metabolism* ; Ethanol/chemistry* ; Interleukin-6/blood* ; Interleukin-1beta/blood*

This study aims to reveal the correlation between the pharmacokinetics(PK) and pharmacodynamics(PD) of multiple components in Epimedii Folium-Chuanxiong Rhizoma and clarify the pharmacodynamic material basis and mechanism of this herb pair in treating osteoarthritis. The Hulth method was used to establish the rat model of osteoarthritis and plasma was collected at various time points after drug administration. The plasma concentrations of multiple components were measured. Enzyme-linked immunosorbent assay(ELISA) was used to measure the plasma concentrations of matrix metalloproteinase(MMP)-3, MMP-13, interleukin-1β(IL-1β), nitric oxide(NO), and tumor necrosis factor-α(TNF-α) as pharmacodynamic indicators. Self-defined weighting coefficients were used to calculate the PK and PD data, and a Sigmoid E_(max) fitting model was used to evaluate the synergistic effect of the compatibility of Epimedii Folium-Chuanxiong Rhizoma. The PK-PD models for Epimedii Folium, Chuanxiong Rhizoma, and Epimedii Folium-Chuanxiong Rhizoma were E=(1.926×C~(2.652))/(0.136 6~(2.652)+C~(2.652)), E=(1.618×C~(345.2))/(0.118 4~(345.2)+C~(345.2)), and E=(2.305×C~(2.786))/(0.240 3~(2.786)+C~(2.786)), respectively. The E_(max) of Epimedii Folium-Chuanxiong Rhizoma was larger than those of the two herbal medicines alone. The EC_(50) of the herb pair was lower than the sum of Epimedii Folium and Chuanxiong Rhizoma alone. The concentrations of MMP-3, MMP-13, IL-1β, NO, and TNF-α were correlated with mass concentrations of multiple components in Epimedii Folium and Chuanxiong Rhizoma, and the compatibility was better than single use. Epimedii Folium, Chuanxiong Rhizoma, and Epimedii Folium-Chuanxiong Rhizoma may play a role in the treatment of osteoarthritis by inhibiting MMP-3, MMP-13, IL-1β, NO, and TNF-α.
Animals ; Rats ; Drugs, Chinese Herbal/pharmacology* ; Male ; Rats, Sprague-Dawley ; Osteoarthritis/metabolism* ; Epimedium/chemistry* ; Interleukin-1beta/blood* ; Tumor Necrosis Factor-alpha/blood* ; Disease Models, Animal ; Nitric Oxide/blood* ; Humans ; Rhizome/chemistry*

OBJECTIVE: To explore the protective effect of glycosaminoglycans (GAG) on vascular endothelium in patients with sepsis. METHODS: A prospective study was conducted on adult patients with sepsis admitted to the intensive care unit (ICU) of Hangzhou Normal University Affiliated Hospital from December 2022 to December 2023. Patients were randomly divided into conventional treatment group and GAG intervention group. Both groups were treated according to the 2021 Surviving Sepsis Campaign Guidelines. The GAG intervention group was additionally treated with GAG (2 mL of sulodexide intramuscular injection once daily for 7 days) on the basis of conventional treatment. Venous blood was collected from patients at 0, 6, 24, 48, 72 hours and 7 days after enrollment to detect serum vascular endothelial glycocalyx [heparan sulfate (HS) and syndecan-1 (SDC-1)], inflammatory markers [C-reactive protein (CRP), procalcitonin (PCT), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6)], and coagulation markers [prothrombin time (PT), activated partial thromboplastin time (APTT), antithrombin-III (AT-III), fibrinogen (Fib), D-Dimer], and to perform acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), and International Society on Thrombosis and Haemostasis (ISTH) scores. The prognosis of patients (length of hospital stay, ICU and 28-day mortality) was observed. The receiver operator characteristic curve (ROC curve) was drawn to evaluate the value of HS in predicting the prognosis of sepsis patients, and the correlation between endothelial glycocalyx degradation products and various clinical indicators was analyzed. RESULTS: A total of 50 adult patients with sepsis meeting the inclusion criteria were enrolled, with 25 in the conventional treatment group and 25 in the GAG intervention group. In terms of degradation products of endothelial glycocalyx, compared to baseline, both groups showed an increasing trend in HS and SDC-1 levels post-treatment. However, the GAG intervention group exhibited significantly lower HS levels at 72 hours and 7 days, as well as lower SDC-1 levels at 6, 24, 48, 72 hours and 7 days compared to the conventional group. Among the surviving patients, the HS levels at 72 hours and SDC-1 levels at 6 hours of treatment in the GAG intervention group were significantly reduced compared to the conventional treatment group. In terms of severity score, compared with before treatment, the GAG intervention group showed a significant decrease in APACHE II, SOFA, and ISTH scores after 7 days of treatment. The SOFA scores of the GAG intervention group after 48 hours and 7 days of treatment were significantly lower than those of the conventional treatment group. In terms of inflammatory indicators, compared with before treatment, the GAG intervention group showed a significant decrease in IL-6 levels after 48 hours of treatment. With the prolongation of treatment time, the CRP levels of both groups of patients showed a significant downward trend, and at 7 days of treatment, the CRP level in the GAG intervention group was significantly lower than that in the conventional treatment group. In terms of coagulation function, with prolonged treatment time, PT and APTT of both groups of patients showed an increasing trend, while Fib showed a decreasing trend. The GAG intervention group showed a significant prolongation of PT after 72 hours of treatment compared to the conventional treatment group. In terms of prognosis, there were no statistically significant differences in ICU and 28-day mortality rates between the two groups. The GAG intervention group had significantly shorter hospital stays than the conventional treatment group. ROC curve analysis showed that HS, CRP, APTT, IL-6, APACHE II, SOFA, and ISTH scores were predictive factors for the prognosis of sepsis patients (all P < 0.05). Compared to a single indicator, the combined detection of multiple indicators has a higher value in predicting the prognosis of sepsis patients [area under the curve (AUC) = 0.911, 95% confidence interval (95%CI) was 0.817-1.000], with a sensitivity of 76.9% and a specificity of 91.9%. Correlation analysis showed that HS was significantly negatively correlated with Fib, PT, TNF-α, IL-6, and PCT (r values were -0.338, -0.396, -0.288, -0.319, and -0.340, all P < 0.05), while HS was significantly positively correlated with D-Dimer and CRP (r values were 0.347 and 0.354, both P < 0.05); SDC-1 was significantly negatively correlated with Fib, PT, APTT, TNF-α, IL-6, and ISTH scores (r values were -0.314, -0.294, -0.408, -0.353, -0.289, -0.287, all P < 0.05). CONCLUSIONS Early glycocalyx degradation can occur in sepsis patients. GAG have a protective effect on,the vascular endothelium, reducing the severity of sepsis and providing organ protection. HS, CRP, APTT, IL-6, APACHE II score, SOFA score, and ISTH score are independent predictive factors for the prognosis of sepsis patients. The combination of HS and the above indicators can significantly improve the accuracy of prediction.
Humans ; Sepsis/blood* ; Glycocalyx/drug effects* ; Glycosaminoglycans/pharmacology* ; Prospective Studies ; Endothelium, Vascular/metabolism* ; Syndecan-1/blood* ; Male ; Female ; C-Reactive Protein/metabolism* ; Interleukin-6/blood* ; Heparitin Sulfate/blood* ; Middle Aged ; Adult ; Tumor Necrosis Factor-alpha/blood* ; Procalcitonin/blood*

OBJECTIVE: To investigate the interaction between α-amylase (α-AMS) and inflammatory response in patients with ventilator-associated pneumonia (VAP) and their predictive value for prognosis. METHODS: A prospective cohort study was conducted. Patients with mechanical ventilation who were treated in the intensive care unit (ICU) of the Second Hospital of Hebei Medical University from June 2020 to June 2023 were enrolled, and the patients were divided into VAP group and non-VAP group according to whether VAP occurred. VAP patients were stratified into mild [acute physiology and chronic health evaluation II (APACHE II) < 10 scores], moderate (APACHE II were 10-20 scores), and severe (APACHE II > 20 scores) groups based on the APACHE II. All patients were followed up for 28 days. In addition, healthy subjects who underwent health examination in our hospital at the same time were selected as the healthy control group. Baseline data including gender, age, mechanical ventilation mode, mechanical ventilation time, underlying diseases, drug use, and laboratory test indicators were collected. The serum levels of α-AMS, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP) and other inflammatory factors were analyzed and compared. Pearson correlation analysis was performed to analyze the correlation between serum α-AMS and inflammatory factors. Logistic regression was used to analyze the influencing factors of poor prognosis in patients with VAP. The receiver operator characteristic curve (ROC curve) was plotted to evaluate the predictive value of α-AMS on the poor prognosis of patients with VAP. RESULTS: A total of 100 mechanically ventilated patients were enrolled, including 60 cases in the VAP group and 40 cases in the non-VAP group. Among the patients with VAP, there were 24 cases in the mild group, 20 cases in the moderate group, and 16 cases in the severe group. A total of 44 patients survived at 28 days, while 16 died. Additionally, 100 healthy individuals were included as the healthy control group. Serum levels of α-AMS, IL-6, TNF-α and CRP in the VAP group were significantly higher than those in the non-VAP group and the healthy control group, while the levels of α-AMS, IL-6, TNF-α and CRP in the non-VAP group were significantly higher than those in the healthy control group. There were statistically significant differences in serum α-AMS, IL-6, TNF-α, CRP levels and APACHE II scores among VAP patients with different disease severities, and the levels of the above indicators in the severe group were significantly higher than those in the moderate group and mild group, and the levels of the above indicators in the moderate VAP group were significantly higher than those in the mild group. Pearson correlation analysis showed that serum α-AMS was positively correlated with IL-6, TNF-α, CRP, and APACHE II scores (r values were 0.404, 0.392 and 0.493, 0.493, all P < 0.01). Univariate analysis showed that age, mechanical ventilation, diabetes mellitus, ventilation time, ventilation position, prophylactic use of antimicrobial drugs, and serum α-AMS, IL-6, TNF-α, CRP, and APACHE II scores were correlated with the prognosis of VAP patients (all P < 0.05). Multivariate Logistic regression analysis identified age [odds ratio (OR) = 1.340, 95% confidence interval (95%CI) was 1.119-1.605], tracheostomy (OR = 3.050, 95%CI was 1.016-9.157), diabetes mellitus (OR = 1.379, 95%CI was 1.102-1.724), and ventilation time ≥ 7 days (OR = 2.557, 95%CI was 1.163-5.623) and serum α-AMS (OR = 1.428, 95%CI was 1.098-1.856), IL-6 (OR = 1.543, 95%CI was 1.005-2.371), TNF-α (OR = 2.228, 95%CI was 1.107-4.485), CRP (OR = 1.252, 95%CI was 1.131-1.387), APACHE II scores (OR = 1.422, 95%CI was 1.033-1.957) were independent influencing factors for the 28-day prognosis of patients with VAP (all P < 0.05). ROC curve analysis demonstrated that serum α-AMS, IL-6, TNF-α and CRP exhibited significant predictive performance on the prognosis of patients with VAP. The best cut-off value for α-AMS had a sensitivity of 81.3%, specificity of 75.0%, and an area under the ROC curve (AUC) of 0.791, which was significantly higher than those of inflammatory markers IL-6, TNF-α, and CRP (P < 0.05). The combined parameter diagnostic performance was significantly better than those of individual parameters (P < 0.05), with the highest diagnostic performance when combined, corresponding to an AUC of 0.868 (95%CI was 0.798-0.938), sensitivity of 87.5%, and specificity of 79.5%. CONCLUSIONS VAP in mechanically ventilated patients can lead to an increase in the levels of peripheral blood α-AMS and inflammatory factors, and there is an interaction between α-AMS and inflammatory markers in severe VAP patients. These markers are closely related to the severity of the disease and prognosis and have significant implications for predicting patient outcomes.
Humans ; Pneumonia, Ventilator-Associated/diagnosis* ; Prognosis ; Prospective Studies ; Respiration, Artificial ; alpha-Amylases/blood* ; Interleukin-6/blood* ; Male ; Female ; C-Reactive Protein/metabolism* ; APACHE ; Inflammation ; Middle Aged ; Intensive Care Units ; Tumor Necrosis Factor-alpha/blood* ; Aged

OBJECTIVE: To analyze the risk factors for ventilator-associated pneumonia (VAP) and its prognosis in patients with severe craniocerebral injury. METHODS: A prospective observational study was conducted. Patients with severe craniocerebral injury admitted to the Second Affiliated Hospital of Xingtai Medical College from January 2020 to December 2022 were enrolled as the study subjects. Patients were divided into VAP group and non-VAP group based on the occurrence of VAP. VAP patients were further stratified into low-risk group [sequential organ failure assessment (SOFA) score 0-5], moderate-risk group (SOFA score 6-8), and high-risk group (SOFA score ≥ 9). General data, serological indicators [interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and signal transducer and activator of transcription 3 (STAT3)], and 28-day prognosis (with mortality as the endpoint event) were compared. Multivariate Logistic regression was used to identify risk factors for VAP and 28-day mortality. Linear regression was applied to analyze the correlations between risk factors and outcomes. RESULTS: A total of 140 patients with severe craniocerebral injury were enrolled, including 49 in the VAP group and 91 in the non-VAP group. The primary cause of injury was traffic accidents, followed by falls and heavy object impacts. Among VAP patients, 38 survived and 11 died within 28 days; 112 were classified as low-risk, 25 as moderate-risk, and 12 as high-risk. Significant differences were observed in age, body mass index (BMI), smoking history, hypertension, diabetes, hyperlipidemia, length of hospital stay, duration of mechanical ventilation, serum albumin levels, and frequency of sputum suction among different subgroups. Serologically, IL-1β, TNF-α, IL-6, and STAT3 mRNA expression levels in the VAP group were significantly higher than those in the non-VAP group. Deceased VAP patients exhibited higher IL-1β, TNF-α, IL-6, and STAT3 mRNA levels compared to survivors. These biomarkers progressively increased from low-risk to high-risk subgroups. Multivariate Logistic regression identified age [odds ratio (OR) were 0.328 and 0.318], BMI (OR were 0.340 and 0.268), hypertension (OR were 0.275 and 0.245), diabetes (OR were 0.319 and 0.307), hyperlipidemia (OR were 0.228 and 0.235), smoking history (OR were 0.255 and 0.240), length of hospital stay (OR were 0.306 and 0.230), duration of mechanical ventilation (OR were 0.247 and 0.219), frequency of sputum suction (OR were 0.325 and 0.228), IL-1β (OR were 0.231 and 0.259), TNF-α (OR were 0.308 and 0.235), IL-6 (OR were 0.298 and 0.277), and STAT3 (OR were 0.259 and 0.265) as independent risk factors for both VAP occurrence and 28-day mortality (all P < 0.05). Correlation analysis revealed that serum albumin levels were negatively correlated with VAP occurrence and mortality (all P < 0.01), while other factors showed positive correlations (all P < 0.01). CONCLUSIONS Age, BMI, length of hospital stay, duration of mechanical ventilation, frequency of sputum suction, hypertension, diabetes, hyperlipidemia, smoking history, IL-1β, TNF-α, and IL-6/STAT3 signaling pathway activation are significantly associated with VAP development and poor prognosis in patients with severe craniocerebral injury, providing a scientific basis for targeted clinical interventions.
Humans ; Risk Factors ; Pneumonia, Ventilator-Associated ; Prognosis ; Prospective Studies ; Craniocerebral Trauma/complications* ; Interleukin-6/blood* ; Male ; Female ; STAT3 Transcription Factor/blood* ; Interleukin-1beta/blood* ; Tumor Necrosis Factor-alpha/blood* ; Middle Aged ; Adult ; Logistic Models

Objective To explore the effect of rehmanniae radix extract(RRE)on chondrocyte apoptosis in the rabbit model of knee osteoarthritis(KOA)by regulating the miR-485-5p/heat shock protein 90 beta family member 1(Hsp90b1)axis.Methods New Zealand rabbits were randomly assigned into control,KOA,low-dose RRE,medium-dose RRE,high-dose RRE,celecoxib,high-dose RRE+antagonist control,and high-dose RRE+miR-485-5p antagonist groups,with 12 rabbits in each group.Rabbits in other groups except the control group were modeled for KOA with the improved Hulth method.After modeling for 8 weeks,the rabbits were administrated with corresponding agents for 4 weeks.The changes in the activity rating of rabbits were recorded.ELISA was employed to measure the levels of tumor necrosis factor-α(TNF-α)and interleukin(IL)-6 in the serum.Safranine O-fast green staining was conducted to reveal the pathological changes in the cartilage tissue and Mankin scoring was performed.TUNEL was employed to detect chondrocyte apoptosis.Real-time fluorescence quantitative PCR was performed to determine the expression of miR-485-5p in the cartilage tissue.Western blot was employed to determine the protein levels of Hsp90b1,cleaved cysteinyl aspartate-specific proteinase-3(Caspase-3),and Bcl2-associated-X(Bax)in the cartilage tissue.The dual-luciferase reporter assay was employed to examine the relationship between miR-485-5p and Hsp90b1.Results Compared with the control group,the KOA group showed down-regulated expression of miR-485-5p,elevated levels of TNF-α and IL-6 in the serum,cartilage erosion and losses,and increases in activity rating,Mankin score,chondrocyte apoptosis rate,and protein levels of Hsp90b1,cleaved Caspase-3,and Bax(all P<0.001).Compared with the KOA group,RRE at low,medium,and high doses,and celecoxib up-regulated the expression of miR-485-5p,lowered the levels of TNF-α and IL-6 in the serum,alleviated the pathological damage to the cartilage tissue,and decreased the activity rating,Mankin score,chondrocyte apoptosis rate,and protein levels of Hsp90b1,cleaved Caspase-3,and Bax(all P<0.05).Compared with the high-dose RRE group and the high-dose RRE+antagonist control group,high-dose RRE+miR-485-5p antagonist down-regulated the expression of miR-485-5p,elevated the levels of TNF-α and IL-6 in the serum,exacerbated the pathological damage to the cartilage tissue,and increased the activity rating,Mankin score,chondrocyte apoptosis rate,and protein levels of Hsp90b1,cleaved Caspase-3,and Bax(all P<0.05).The results indicated that there was a targeted regulatory relationship between miR-485-5p and Hsp90b1.Conclusion RRE may inhibit the expression of Hsp90b1 by up-regulating miR-485-5p,thereby inhibiting chondrocyte apoptosis in the rabbit model of KOA.
Animals ; Rabbits ; Apoptosis/drug effects* ; Chondrocytes/pathology* ; Osteoarthritis, Knee/drug therapy* ; MicroRNAs/metabolism* ; Rehmannia/chemistry* ; Disease Models, Animal ; Tumor Necrosis Factor-alpha/blood* ; Plant Extracts/pharmacology* ; Interleukin-6/blood* ; HSP90 Heat-Shock Proteins/metabolism* ; Male ; Drugs, Chinese Herbal/pharmacology*

Objective To investigate the effect and mechanism of baicalin on blood lipid metabolism and immune function in rats with gestational diabetes mellitus (GDM). Methods Female rats fed with high-fat and high-sugar diet and male rats fed with ordinary diet were caged together to prepare pregnant rats, and the GDM rat model was established by intraperitoneal injection of streptozotocin (35 mg/kg). GDM rats were randomly divided into a model group, a fasudil (FA) (RhoA/RocK inhibitor) group (10 mg/kg), low-dose (100 mg/kg) and high-dose (200 mg/kg) baicalin groups, and a high-dose baicalin combined with LPA (RhoA/RocK activator) group (200 mg/kg baicalin+1 mg/kg LPA ), with 12 rats in each group. Another 12 pregnant rats fed with high-fat and high-sugar diet were selected as the control group. After 2 weeks of corresponding drug intervention in each group, the level of fasting blood glucose (FBG) was detected by blood glucose meter. The level of fasting insulin (FINS) in serum was detected by ELISA, and the insulin resistance index (HOMA-IR) was calculated. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) in serum, and the levels of immunomodulator tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and IL-10 in peripheral blood were detected by the kit. The histopathological changes of liver were observed by HE staining. The proportion of T lymphocyte subsets in peripheral blood was detected by flow cytometry. The mRNA and protein expressions of Ras homolog gene family member A (RhoA), Rho associated coiled-coil forming protein kinase 1 (ROCK1), and ROCK2 in liver tissue were detected by real-time quantitative PCR and Western blot. Results Compared with the control group, the levels of FBG, FINS, HOMA-IR, ALT, AST, TG, TC, and LDL-C in serum, the levels of TNF-α, IL-6, the percentage of CD8⁺T cell in peripheral blood, and the mRNA and protein expression of RhoA, ROCK1, and ROCK2 in liver tissue in the model group were higher; the level of HDL-C in serum, the percentage of IL-10 levels, CD3⁺T cells, CD4⁺T cell, and CD4⁺T/CD8⁺T ratio in peripheral blood were lower. Compared with the model group, the levels of FBG, FINS, HOMA-IR, ALT, AST, TG, TC, and LDL-C in serum, the levels of TNF-α, IL-6, the percentage of CD8⁺T cell in peripheral blood, and the mRNA and protein expression of RhoA, ROCK1, and ROCK2 in liver tissue in the the FA group and low-dose and high-dose baicalin groups were lower; the level of HDL-C in serum, IL-10 level, the percentage of CD3⁺T cells, CD4⁺T cell, and CD4⁺T/CD8⁺T ratio in peripheral blood were higher. LPA could obviously weaken the improvement effects of baicalin on blood lipid metabolism and immune function in GDM rats. Conclusion Baicalin may improve blood lipid metabolism and immune function in GDM rats by inhibiting the RhoA/ROCK pathway.
Animals ; Female ; Diabetes, Gestational/metabolism* ; Pregnancy ; rho-Associated Kinases/genetics* ; Flavonoids/pharmacology* ; Rats ; rhoA GTP-Binding Protein/genetics* ; Lipid Metabolism/drug effects* ; Male ; Signal Transduction/drug effects* ; Rats, Sprague-Dawley ; Blood Glucose/metabolism* ; Lipids/blood* ; Tumor Necrosis Factor-alpha/blood* ; rho GTP-Binding Proteins