Objective To evaluate tolerability,safety and pharmacokinetics of JS026 and JS026-JS016 single dose intravenous infusion in healthy adults.Methods This phase 1,randomized,double-blind,placebo-controlled,dose-escalation study totally included 48 participants:32 healthy subjects were enrolled in JS026 single intravenous infusion groups and 16 healthy subjects were enrolled in JS026-JS016 groups.JS026 was sequentially administered from low dose to high dose(30-1 000 mg),with intravenous infusion of JS026 or placebo in JS026 single-dose groups,and intravenous infusion of JS026-JS016 or placebo in the combination drug groups.Blood was collected according to the time point designed for trial.Serum concentrations of JS026 and JS016 were determined by enzyme linked immunosorbnent assay(ELISA),and pharmacokinetics parameters were calculated by WinNonlin 8.2.The power model method was used to evaluate the linear analysis of dose and drug exposure.Results 47 subjects completed trial and 1 subject lost to follow-up.After a single intravenous injection of JS026 of 30 mg,100 mg,300 mg,600 mg,and 1 000 mg,mean Cmax were(9.47±1.53),(33.20±4.95),(96.10±13.70),(177.00±22.20)and(353.00±56.70)μg·mL-1,respectively;mean AUC0-∞ were(4 225.00±607.00),(1.78 × 104±3 268.00),(5.83 × 104±1 038.00),(1.07 × 105±152.00),(1.66 × 105±327.00)μg·h·mL-1,respectively;mean t1/2 of JS026 were 563-709 h.The Cmax and AUC0-∞ of JS026 were basically similar alone or in combination with JS016.The results of Power model showed that Cmax and AUC0-∞ increased approximately linearly with the increasing dose of JS026.Treatment emergent adverse event was not increasing when dose increased and most of adverse event associated with drugs were abnormal on laboratory tests and haematuria,thus JS026 and JS016 was well tolerated in all groups.Conclusion The single intravenous infusion of JS026 can almost be thought to be a linear relationship between the doses and drug serum exposure.JS016 had no significant effect on serum concentration of JS026 and JS026 was well tolerated and safe in healthy subjects within 30-1 000 mg.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

This study aims to explore the anti-depression mechanism of Zuojin Pills based on the plasma constituents, network pharmacology, and experimental verification. UHPLC-TOF-MS was used for qualitative analysis of Zuojin Pills-containing serum. Targets of the plasma constituents and the disease were retrieved from PharmMapper and GeneCards. Then the protein-protein interaction(PPI) network was constructed and core targets were screened for GO term enrichment and KEGG pathway enrichment. Cytoscape 3.7.2 was employed construct the "compound-target-pathway" network and the targets and signaling pathways of Zuojin Pills against depression were predicted. CUMS-induced depression mouse model was established to verify the key targets. The results showed that a total of 21 constituents migrating to blood of Zuojin Pills were identified, which were mainly alkaloids. A total of 155 common targets of the constituents and the disease and 67 core targets were screened out. KEGG enrichment and PPI network analysis showed that Zuojin Pills may play a role in the treatment of depression through AMPK/SIRT1, NLRP3, insulin and other targets and pathways. Furthermore, the results of animal experiments showed that Zuojin Pills could significantly improve the depression behaviors of depression, reduce the levels of IL-1β, IL-6 and TNF-α in hippocampus and serum, activate AMPK/SIRT1 signaling, and reduce the protein expression of NLRP3. In conclusion, Zuojin Pills may play a role in the treatment of depression by activating AMPK/SIRT1 signaling pathway, and inhibiting NLRP3 activation and neuroinflammation in the hippocampus of mice.
Animals ; Mice ; Network Pharmacology ; AMP-Activated Protein Kinases ; Chromatography, High Pressure Liquid ; NLR Family, Pyrin Domain-Containing 3 Protein ; Sirtuin 1 ; Drugs, Chinese Herbal/pharmacology* ; Molecular Docking Simulation

Autologous ozonized blood transfusion(AOBT) is a therapy of re-transfusion of 100-200 mL of autologous blood after shaking and agitation with appropriate amount of oxygen-ozone in vitro. The oxidation of blood through the strong oxidation of ozone can enhance the non-specific immune response of the body, regulate the internal environment and promote health. This therapy has been increasingly applied in clinical practice, while no unified standard for the operation process in terms of ozone concentration, treatment frequency and treatment course had been established. This operation process of AOBT is primarily explored in order to standardize the operation process and ensure its safety and efficacy.

During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.

The value of combined detection of neutrophil apolipoprotein (HNL), serum amyloid A (SAA), procalcitonin (PCT) and C-reactive protein (CRP) in the differential diagnosis of bacterial and viral infectious diseases. A retrospective study was conducted to collect the clinical data of infected patients and healthy people in the clinical department of Shaanxi Provincial People's Hospital from September to December in 2022. 100 patients with confirmed infection were divided into bacterial infection group (n=50) and virus infection group (n=50), and 50 healthy people were selected as control group (n=50). Fasting venous blood was collected at the initial stage of admission or on the day of physical examination. HNL was detected by double antibody sandwich method, SAA and CRP were detected by nephelometry, and PCT was detected by chemiluminescence method. The efficacy of infection markers in the differential diagnosis of bacterial infection and viral infection in infected patients was evaluated. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of HNL, SAA, PCT and CRP in bacterial and viral infectious diseases; Logistic regression was used to analyze the influence of each index on the diagnostic efficiency. The results showed that the levels of HNL (126.60±33.32) ng/ml, PCT (28.02±11.37) ng/ml and CRP (36.13±14.37) mg/L in bacterial infection group were significantly higher than those of HNL (47.72±15.94) ng/ml, PCT (1.27±0.40) ng/ml, CRP (18.77±10.66) mg/L in virus group and HNL (38.21±12.53) ng/ml, PCT (0.38±0.12) ng/ml and CRP (4.13±1.07) mg/L in control group. The level of HNL increased most significantly (F=89.228, P<0.05). The area under ROC curve (AUC) from large to small was HNL+SAA+PCT+CRP (0.976), HNL (0.907), PCT (0.885), CRP (0.856), SAA (0.790), SAA/CRP (0.733). The level of SAA/CRP in virus infection group (94.05±3.75) was significantly higher than that in bacteria group (17.70±3.69) and control group (3.89±1.50) (F=84.005, P<0.05). The area under ROC curve (AUC) from large to small was HNL+SAA+PCT+CRP (0.986), SAA/CRP (0.956), SAA (0.878), HNL (0.768), CRP (0.742), PCT (0.730). In conclusion, HNL has the best auxiliary diagnostic efficacy in bacterial infection, followed by PCT; SAA/CRP has the best auxiliary diagnostic efficacy in viral infection, followed by SAA; the combined detection of serum HNL, SAA, PCT and CRP may be helpful for the differential diagnosis of bacterial and viral infections.
Humans ; C-Reactive Protein ; Procalcitonin ; Serum Amyloid A Protein ; Retrospective Studies ; Virus Diseases/diagnosis* ; Bacteria ; Communicable Diseases ; Bacterial Infections/diagnosis*

The value of combined detection of neutrophil apolipoprotein (HNL), serum amyloid A (SAA), procalcitonin (PCT) and C-reactive protein (CRP) in the differential diagnosis of bacterial and viral infectious diseases. A retrospective study was conducted to collect the clinical data of infected patients and healthy people in the clinical department of Shaanxi Provincial People's Hospital from September to December in 2022. 100 patients with confirmed infection were divided into bacterial infection group (n=50) and virus infection group (n=50), and 50 healthy people were selected as control group (n=50). Fasting venous blood was collected at the initial stage of admission or on the day of physical examination. HNL was detected by double antibody sandwich method, SAA and CRP were detected by nephelometry, and PCT was detected by chemiluminescence method. The efficacy of infection markers in the differential diagnosis of bacterial infection and viral infection in infected patients was evaluated. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of HNL, SAA, PCT and CRP in bacterial and viral infectious diseases; Logistic regression was used to analyze the influence of each index on the diagnostic efficiency. The results showed that the levels of HNL (126.60±33.32) ng/ml, PCT (28.02±11.37) ng/ml and CRP (36.13±14.37) mg/L in bacterial infection group were significantly higher than those of HNL (47.72±15.94) ng/ml, PCT (1.27±0.40) ng/ml, CRP (18.77±10.66) mg/L in virus group and HNL (38.21±12.53) ng/ml, PCT (0.38±0.12) ng/ml and CRP (4.13±1.07) mg/L in control group. The level of HNL increased most significantly (F=89.228, P<0.05). The area under ROC curve (AUC) from large to small was HNL+SAA+PCT+CRP (0.976), HNL (0.907), PCT (0.885), CRP (0.856), SAA (0.790), SAA/CRP (0.733). The level of SAA/CRP in virus infection group (94.05±3.75) was significantly higher than that in bacteria group (17.70±3.69) and control group (3.89±1.50) (F=84.005, P<0.05). The area under ROC curve (AUC) from large to small was HNL+SAA+PCT+CRP (0.986), SAA/CRP (0.956), SAA (0.878), HNL (0.768), CRP (0.742), PCT (0.730). In conclusion, HNL has the best auxiliary diagnostic efficacy in bacterial infection, followed by PCT; SAA/CRP has the best auxiliary diagnostic efficacy in viral infection, followed by SAA; the combined detection of serum HNL, SAA, PCT and CRP may be helpful for the differential diagnosis of bacterial and viral infections.
Humans ; C-Reactive Protein ; Procalcitonin ; Serum Amyloid A Protein ; Retrospective Studies ; Virus Diseases/diagnosis* ; Bacteria ; Communicable Diseases ; Bacterial Infections/diagnosis*

Objective: To evaluate the diagnostic value and application of 24 h multichannel intraluminal impedance-pH (24 h MII-pH) monitoring in children with gastroesophageal reflux disease (GERD). Methods: This is a cross-sectional study. From January 2013 to December, 2020, 417 patients who received 24 h MII-pH monitoring in Department of Gastroenterology of Children's Hospital Capital Institute of Pediatrics were included. According to results, these children were divided into the GERD and non-GERD groups. Furthermore, the 132 children with GERD who had gastroscopy were divided into the reflux esophagitis (RE) and non-erosive reflux disease (NE) groups to investigate the differences in their refluxes. Non-parametric Mann-Whitney U test or indepentent sample t test was used for comparisons between the groups. Results: Among the 417 children, 232 were males and 185 females, aged (7.3±3.9) years. The course of disease was 0.5 (0.1, 2.0) years. The main clinical symptoms included acid reflux (128 cases), vomiting (173 cases), abdominal pain (101 cases), and cough (76 cases). The 24 h MII-pH monitoring were positive in 243 children (58.3%, 243/417), which was higher than that by 24 h esophageal pH monitoring (43.6%, 182/417). The 24 h MII-pH monitoring results demonstrated significant differences in the episodes of acid reflux, weakly acidic reflux, non-acidic reflux, liquid reflux and mixed reflux between GERD and non-GERD groups (10 (4, 19) vs. 4 (1, 9) times/24 h, 14 (6, 32) vs. 7 (3, 13) times/24 h, 0 (0, 0) vs. 0 (0, 0) times/24 h, 19 (10, 34) vs. 8 (3, 14) times/24 h, and 6 (2, 12) vs. 3 (1, 5) times/24 h, Z=-6.96, -7.25, -5.62, -8.75, and -6.48, all P<0.05, respectively). Besides, the results also showed significant differences in Boix-Ochoa score, episodes of long reflux, course of long reflux, and episodes of weakly acidic reflux between the RE and NE groups (51.2 (21.4, 153.2) vs. 20.7 (12.1, 34.7), 5 (2, 10) vs. 1 (0, 4) times/24 h, 19 (7, 87) vs. 8 (3, 22) min, and 5 (2, 15) vs. 15 (6, 33) times/24 h, Z=-3.44, -3.41, -2.65, and -2.27, all P<0.05, respectively). Conclusion: 24 h MII-pH monitoring not only improves the detection rate of GERD in children, but also provides a possibility to early etiological diagnosis.
Female ; Male ; Humans ; Child ; Cross-Sectional Studies ; Electric Impedance ; Gastroesophageal Reflux/diagnosis* ; Esophageal pH Monitoring ; Hydrogen-Ion Concentration

OBJECTIVE: To evaluate the protective effect of excretory-secretory proteins from Trichinella spiralis muscle larvae (Ts-MES) on sepsis-induced myocardial injury in mice. METHODS: Eighty male BALB/C mice were randomized equally into sham-operated group, myocardial injury group, Ts-MES treatment group and dexamethasone treatment group. In the latter 3 groups, sepsis-induced myocardial injury models were established by cecal ligation and perforation; the sham operation was performed by exposure of the cecum without ligation or perforation. Forty minutes after the operation, the mice were given intraperitoneal injections 150 μL PBS, 20 μg TS-MES or 0.3 mg/kg dexamethasone as indicated. At 12 h after the operation, 6 mice were randomly selected from each group for echocardiography, and 8 mice were used for observing the survival rate within 72 h. The remaining 6 mice were examined for myocardial pathologies with HE staining and serum levels of NTPro-BNP and cTnI with ELISA; the expressions of TNF-α, IL-6, IL-10 and TGF-β in the serum and myocardial tissue were detected using ELISA and qRT-PCR. RESULTS: Compared with the sham-operated mice, the septic mice showed significantly decreased cardiac function indexes (LVEF, LVFS, and E/A) with lowered survival rate within 72 h (P < 0.001) and significantly higher myocardial injury scores and serum levels of NTPro-BNP and cTnI (P < 0.01). Treatment with TS-MES significantly improved the cardiac function and 72-h survival rate (P < 0.05) and lowered the myocardial injury scores and serum levels of NTPro-BNP and cTnI (P < 0.05) in the septic mice. Compared with the sham-operated mice, the septic mice had obviously increased TNF-α and IL-6 levels in the serum and myocardial tissue (P < 0.001), which were significantly lowered by treatment with TS-MES (P < 0.05). TS-MES and dexamethasone both increased the levels of IL-10 and TGF-β in the septic mice, but the changes were significant only in TS-MES-treated mice (P < 0.05). CONCLUSION Ts-MES are capable of protecting against myocardial injury in septic mice by reducing the production of pro-inflammatory cytokines and enhancing the levels of regulatory cytokines.
Animals ; Cytokines ; Dexamethasone ; Heart Injuries ; Interleukin-10 ; Interleukin-6 ; Larva ; Male ; Mice ; Mice, Inbred BALB C ; Myocardium ; Sepsis ; Transforming Growth Factor beta ; Trichinella spiralis ; Tumor Necrosis Factor-alpha

Malocclusion is one of the three most common oral diseases reported by World Health Organization(WHO). In China, its incidence rate is rising. Malocclusion seriously affects the dental and maxillofacial function, facial appearance and growth development of nearly 260 million children in China, and what is more, it affects their physical and mental health development. Malocclusion occurrence is related to genetic and environmental factors. Early treatment of malocclusion can create a good dental and maxillofacial development environment, correct abnormal growth and control the adverse effects of abnormal genetic factors. It can effectively reduce the prevalence of children's malocclusion and enhance their physical and mental health. This is an urgent need from the economic perspective of our society, so it has great practical and social significance. Experts from the project group "standard diagnose and treatment protocols for early orthodontic intervention of malocclusions of children" which initiated by China National Health Institute of Hospital Administration wrote the "China Experts' Consensus on Preventive and Interceptive Orthodontic Treatments of Malocclusions of Children", which aims to guide and popularize the clinical practice, improve the clinical theory and practice level, and accelerate the disciplinary development of early treatment of children's malocclusion in China. The consensus elaborates the harmfulness of malocclusion and the necessity of early treatment, and brings up the principles and fundamental contents. Based on the law of dental and maxillofacial development, this paper puts forward the guiding suggestions of preventive and interceptive treatments in different stages of dental development ranging from fetus to early permanent dentition. It is a systematic project to promote and standardize the early treatment of malocclusion. Through scientific and comprehensive stratified clinical practice and professional training, the clinical system of early treatment of malocclusion in China will eventually be perfected, so as to comprehensively care for children's dental and maxillofacial health, and improve their oral and physical health in China.
Child ; China/epidemiology* ; Consensus ; Dental Care ; Humans ; Malocclusion/prevention & control* ; Orthodontics, Interceptive