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 explore the relationship between serum chloride levels and prognosis in patients with hepatic coma in the intensive care unit (ICU). METHODS: We analyzed 545 patients with hepatic coma in the ICU from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Associations between serum chloride levels and 28-day and 1-year mortality rates were assessed using restricted cubic splines (RCSs), Kaplan-Meier (KM) curves, and Cox regression. Subgroup analyses, external validation, and mechanistic studies were also performed. RESULTS: A total of 545 patients were included in the study. RCS analysis revealed a U-shaped association between serum chloride levels and mortality in patients with hepatic coma. The KM curves indicated lower survival rates among patients with low chloride levels (< 103 mmol/L). Low chloride levels were independently linked to increased 28-day and 1-year all-cause mortality rates. In the multivariate models, the hazard ratio ( HR) for 28-day mortality in the low-chloride group was 1.424 (95% confidence interval [ CI]: 1.041-1.949), while the adjusted hazard ratio for 1-year mortality was 1.313 (95% CI: 1.026-1.679). Subgroup analyses and external validation supported these findings. Cytological experiments suggested that low chloride levels may activate the phosphorylation of the NF-κB signaling pathway, promote the expression of pro-inflammatory cytokines, and reduce neuronal cell viability. CONCLUSION Low serum chloride levels are independently associated with increased mortality in patients with hepatic coma.
Humans ; Male ; Female ; Middle Aged ; Intensive Care Units ; Prognosis ; Chlorides/blood* ; Aged ; Coma/blood* ; Adult

It is necessary to develop rapid and living guidelines in order to improve the evidence translation and guidance for clinical practice in emergency situations， and to enhance the participation of traditional Chinese medicine （TCM） in management of emergencies. This paper introduced the process of developing rapid and living guidelines of TCM and divided it into three stages， that is preparation， rapid development and dynamic updating， which highlights the features of rapid development， high quality， and dynamic updating and the integration with the predominance of TCM. By comparing with general guidelines on composition， personnel number， timing to formulate and communication patterns of the guideline working groups， as well as the content and number of clinical questions， this paper mainly gave suggestions on how to formulate a concise but authoritative team during the preparation stage， how to efficiently manage the guideline team and promote the development process from conflict of interest management， working and communication mode adjustment， and how to formulate and update the important and prioritized clinical questions， all of which may provide reference for the development of TCM rapid and living guidelines.

The lack of direct evidence is an important problem faced in the formation of recommendations in rapid living guidelines of traditional Chinese medicine under public health emergencies， and the supplementation of indirect evidence can be a key method to solve this problem. For the collection of evidence， the type of evidence required， including direct and indirect evidence， should be clarified， and ‘direct first’ principle for selecting evidence can be set to standardize and accelerate the guideline development. When integrating evidence， recommendations can be formed directly if there is sufficient direct evidence， while regarding insufficient direct evidence， recommendations need to be supplemented and improved by integrating indirect evidence. In addition， when the body of evidence contains evidence from multiple sources， it is suggested to rate the evidence according to “higher rather than lower” principle. Finally， when forming recommendations， the level of evidence， safety and economic efficiency should be taken into consideration to determine the strength of the recommendation.

Objective:To explore the relation of behavioral inhibition system/behavioral activation system and affects in college students,and to analyze the parallel mediating role of facets of mindfulness in their relationship.Methods:Totally 268 college students were selected and assessed with the Five Facets Mindfulness Questionnaire,Behavioral Inhibition System and Behavioral Activation System Scale,Positive and Negative Affect Scale.The mediating effect of different mindfulness factors on the relationship between behavioral inhibition sys-tem/behavioral activation system and affects was examined using linear regression analysis and biased-corrected bootstrap confidence interval.Results:The factors of describe and non-reactivity mediated the relationship between the behavioral activation system and positive affects(effect=0.04,0.02),while the factors of act with awareness,non-judging and non-reactivity mediated the relationship between the behavioral inhibition system and negative af-fects(effect=0.09,0.06,0.04).Conclusion:The behavioral inhibition system/behavioral activation system may be related to negative affect and positive affect respectively.As a particular emotion regulation strategy,mindfulness factors play a unique mediating role in the relationship between behavioral inhibition system/behavioral activation system and affects.

OBJECTIVE: Clinical characteristics and outcome in COVID-19 with brucellosis patients has not been well demonstrated, we tried to analyze clinical outcome in local and literature COVID-19 cases with brucellosis before and after recovery. METHODS: We retrospectively collected hospitalization data of comorbid patients and prospectively followed up after discharge in Heilongjiang Infectious Disease Hospital from January 15, 2020 to April 29, 2022. Demographics, epidemiological, clinical symptoms, radiological and laboratory data, treatment medicines and outcomes, and follow up were analyzed, and findings of a systematic review were demonstrated. RESULTS: A total of four COVID-19 with brucellosis patients were included. One patient had active brucellosis before covid and 3 patients had nonactive brucellosis before brucellosis. The median age was 54.5 years, and all were males (100.0%). Two cases (50.0%) were moderate, and one was mild and asymptomatic, respectively. Three cases (75.0%) had at least one comorbidity (brucellosis excluded). All 4 patients were found in COVID-19 nucleic acid screening. Case C and D had only headache and fever on admission, respectively. Four cases were treated with Traditional Chinese medicine, western medicines for three cases, no adverse reaction occurred during hospitalization. All patients were cured and discharged. Moreover, one case (25.0%) had still active brucellosis without re-positive COVID-19, and other three cases (75.0%) have no symptoms of discomfort except one case fell fatigue and anxious during the follow-up period after recovery. Conducting the literature review, two similar cases have been reported in two case reports, and were both recovered, whereas, no data of follow up after recovery. CONCLUSION These cases indicate that COVID-19 patients with brucellosis had favorable outcome before and after recovery. More clinical studies should be conducted to confirm our findings.
Female ; Humans ; Male ; Middle Aged ; Brucellosis ; COVID-19 ; Retrospective Studies ; SARS-CoV-2 ; Treatment Outcome ; Case Reports as Topic

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Tianshu" (ST 25) and "Shangjuxu" (ST 37) on mental state, visceral sensitivity and protein expression of nerve growth factor (NGF), tyrosine kinase receptor A (TrkA) and transient receptor potential vanilloid 1 (TRPV1) of colonic tissue in diarrhea-predominant irritable bowel syndrome (IBS-D) rats, and to explore its possible mechanism on treating IBS-D. METHODS: A total of 36 male SD rats of SPF grade were randomized into a blank group, a model group, an EA group and a western medication group, 9 rats in each group. In the model group, the EA group and the western medication group, IBS-D model was established by enema of dinitrobenzene sulfonic acid (DNBS) combined with chronic restraint stress method. In the EA group, EA was applied at "Tianshu" (ST 25) and "Shangjuxu" (ST 37), with disperse-dense wave, in frequency of 2 Hz/100 Hz, 20 min each time, once a day for 7 days. In the western medication group, pinaverium bromide suspension was given by gavage (15 mg•kg^-1•d^-1) for 7 days. Before and after model establishment, and after intervention, the body mass, 24 h food intake and fecal water content were observed, the visceral sensitivity was detected by abdominal withdrawal reflex (AWR); after intervention, the mental state was evaluated by elevated plus maze (EPM) test, the protein expression of NGF, TrkA and TRPV1 was detected by immunohistochemistry and Western blot in the 4 groups. RESULTS: After model establishment, compared with the blank group, the body mass and 24 h food intake were decreased (P<0.05), first systolic latency of AWR was shortened and number of contraction wave of AWR was increased (P<0.05), and fecal water content was increased (P<0.05) in the model group, the EA group and the western medication group. After intervention, compared with the blank group, open arm residence time ratio (OT%) of EPM was decreased (P<0.05) and protein expression of NGF, TrkA, TRPV1 in colonic tissue was increased in the model group (P<0.05); compared with the model group, the body mass and 24 h food intake were increased (P<0.05), first systolic latency of AWR was lengthened and number of contraction wave of AWR was decreased (P<0.05), the fecal water content was decreased (P<0.05), OT% of EPM was increased (P<0.05), and protein expression of NGF, TrkA, TRPV1 in colonic tissue was decreased (P<0.05) in the EA group and the western medication group. CONCLUSION Electroacupuncture at "Tianshu" (ST 25) and "Shangjuxu" (ST 37) can relieve the anxiety and depression-like behaviors in IBS-D rats, down-regulate the protein expression of NGF, TrkA, TRPV1 in colonic tissue, so as to reduce the visceral sensitivity and relieve symptoms.
Male ; Rats ; Animals ; Receptor Protein-Tyrosine Kinases ; Rats, Sprague-Dawley ; Irritable Bowel Syndrome/therapy* ; Sulfonic Acids ; Nerve Growth Factors ; TRPV Cation Channels/genetics*

Objective:To explore the guiding effect of peripheral perfusion index (PI) on fluid resuscitation in patients with septic shock.Methods:Sixty-five patients with septic shock who were diagnosed according to relevant criteria of septic shock and admitted to the department of critical care medicine of the Affiliated Hospital of Hangzhou Normal University from September 2017 to December 2020 were included. Patients were divided into the conventional treatment group (30 cases) and PI guidance group (35 cases) by random number method. Both groups of patients were treated with the bundle according to clinical guidelines. Sputum, urine and blood were collected for pathogenic microorganism culture before the application of antibiotics, and vasoactive drugs were given. Both groups need to achieve all the following resuscitation goals within 6 hours: urine output > 0.5 mL·kg -1·h -1, mean arterial pressure (MAP) ≥ 65 mmHg (1 mmHg ≈ 0.133 kPa), central venous pressure (CVP) was 8-12 mmHg, and central venous oxygen saturation (ScvO 2) ≥ 0.70. There was no further resuscitation in the conventional treatment group after the goals were achieved. In addition to these four goals, the PI guidance group was expected to achieve PI≥ 1.4. Heart rate (HR), CVP, MAP, ScvO 2, blood lactic acid (Lac), the time of fluid negative balance, intensive care unit (ICU) mortality and 28-day mortality between the two groups were compared before and after 6 hours of fluid resuscitation. Results:Before fluid resuscitation, there were no statistically significant differences in all indicators between two groups. After 6 hours fluid resuscitation, the four treatment goals in PI guidance group were slightly lower than those of the conventional treatment group [HR (times/min): 96.5±12.1 vs. 97.7±7.9, MAP (mmHg): 83.2±6.2 vs. 82.1±7.5, ScvO 2: 0.661±0.077 vs. 0.649±0.051, CVP (mmHg): 10.8±2.7 vs. 10.4±2.1], there were no statistically significant differences between the two groups (all P > 0.05); the Lac level of the PI guidance group after resuscitation was lower than that of the conventional treatment group, and the difference was statistically significant (mmol/L: 4.8±1.3 vs. 5.9±1.4, P < 0.05); the duration of fluid negative balance in the PI guidance group was earlier than that in the conventional treatment group [days: 3.0 (2.0, 3.0) vs. 3.5 (3.0, 4.0), P < 0.05]. The ICU mortality and 28-day mortality in the PI guidance group were lower than those in the conventional treatment group [ICU mortality rate: 37.1% (13/35) vs. 50.0% (15/30), 28-day mortality rate: 57.1% (20/35) vs. 60.0% (18/30)], but the differences were not statistically significant (both P > 0.05). Conclusions:The peripheral PI can be used as an important indicator of fluid resuscitation in patients with septic shock. PI guiding fluid resuscitation in patients with septic shock can reduce Lac levels, shorten the duration of fluid negative balance and reduce the risk of fluid overload.

Objective Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are major public health and social issues worldwide. The long-term follow-up of COVID-19 with pulmonary TB (PTB) survivors after discharge is unclear. This study aimed to comprehensively describe clinical outcomes, including sequela and recurrence at 3, 12, and 24 months after discharge, among COVID-19 with PTB survivors. Methods From January 22, 2020 to May 6, 2022, with a follow-up by August 26, 2022, a prospective, multicenter follow-up study was conducted on COVID-19 with PTB survivors after discharge in 13hospitals from four provinces in China. Clinical outcomes, including sequela, recurrence of COVID-19, and PTB survivors, were collected via telephone and face-to-face interviews at 3, 12, and 24 months after discharge. Results Thirty-two COVID-19 with PTB survivors were included. The median age was 52 (45, 59) years, and 23 (71.9％) were men. Among them, nearly two-thirds (62.5％) of the survivors were moderate, three (9.4％) were severe, and more than half (59.4％) had at least one comorbidity (PTB excluded). The proportion of COVID-19 survivors with at least one sequela symptom decreased from 40.6％ at 3 months to 15.8％ at 24 months, with anxiety having a higher proportion over a follow-up. Cough and amnesia recovered at the 12-month follow-up, while anxiety, fatigue, and trouble sleeping remained after 24 months. Additionally, one (3.1％) case presented two recurrences of PTB and no re-positive COVID-19 during the follow-up period. Conclusion The proportion of long symptoms in COVID-19 with PTB survivors decreased over time, while nearly one in six still experience persistent symptoms with a higher proportion of anxiety. The recurrence of PTB and the psychological support of COVID-19 with PTB after discharge require more attention.

Objective To investigate the dosimetric differences between volumetric modulated arc therapy (VMAT) with a flattening filter (FF) and flattening filter-free (FFF) VMAT in fractionated stereotactic radiotherapy for brain metastases. Methods Seventeen patients with brain metastases were divided into FF-VMAT group (VMAT plans with the FF mode) and FFF-VMAT group (VMAT plans with the FFF mode). The two groups were compared in terms of target volume dose parameters (D_98%, D_2% and D_mean), the conformal index (CI), the gradient index (GI), the gradient, normal brain tissue dose parameters (V_5Gy, V_10Gy, V_12Gy and D_mean), monitor units, and beam-on time. Results Compared with the FF-VMAT group, the FFF-VMAT group had significantly lower GI (3.33 ± 0.37 vs 3.27 ± 0.35, P = 0.001), a significantly lower gradient [(0.85 ± 0.20) cm vs (0.84 ± 0.19) cm, P = 0.002], a significantly shorter beam-on time [(177.05 ± 62.68) s vs (142.71 ± 34.59) s, P = 0.001], and significantly higher D_2% [(65.69 ± 2.15) Gy vs (66.99 ± 2.03) Gy, P = 0.001] and D_mean [(58.77 ± 1.60) Gy vs (59.95 ± 1.43) Gy, P <0.001]. There were no significant differences in the CI, the D_98% of the target volume, the V_5Gy, V_10Gy, V_12Gy and D_mean of the normal brain tissue, and monitor units between FFF-VMAT and FF-VMAT. Conclusion FFF-VMAT can better protect the normal tissue around the target volume, reduce the beam-on time, and improve treatment efficiency.