Objective: To investigate the characteristics of pharmacokinetic (PK) and pharmacodynamic (PD) parameters of antibacterial agents in children with sepsis treated by extracorporeal membrane oxygenation (ECMO). Methods: In this prospective cohort study, 20 children with sepsis (confirmed or suspected) who were treated with ECMO and antimicrobial in the Department of Critical Medicine of Hunan Children's Hospital from March 2021 to December 2022 were enrolled as the ECMO group. Through therapeutic drug monitoring (TDM), the PK-PD parameters of antibacterial agents were analyzed. Twenty five children with sepsis in the same department who were treated with vancomycin but no ECMO at the same time were enrolled as the control group. The individual PK parameters of vancomycin were calculated by Bayesian feedback method. The PK parameters in the two groups were compared, and the correlation between trough concentration and area under the curve (AUC) was analyzed. Wilcoxon rank sum test was used for inter group comparison. Results: Twenty patients in the ECMO group, included 6 males and 14 females, with an onset age of 47 (9, 76) months. In the ECMO group, 12 children (60%) were treated with vancomycin, and the trough concentration was less than 10 mg/L in 7 cases, 10-20 mg/L in 3 cases, and >20 mg/L in 2 cases; AUC/minimum inhibitory concentration (MIC) (MIC=1 mg/L)<400 was in 1 case, 400-600 in 3 cases, and >600 in 8 cases. Among the 11 children (55%) who were treated with β-lactam antibiotics, there were 10 cases with drug concentration at 50% dosing interval (C_T50)>4 MIC and 9 cases with trough concentration>MIC, both C_T50 and trough concentration of cefoperazone reached the target. Among the 25 cases of control group, 16 were males and 9 females, with an onset age of 12 (8, 32) months. There was a positive correlation between vancomycin trough concentration and AUC (r²=0.36, P<0.001). The half-life of vancomycin and the 24-hour AUC (AUC_{0-24 h}) in the ECMO group were higher than those in the control group (5.3 (3.6, 6.8) vs. 1.9 (1.5, 2.9) h, and 685 (505, 1 227) vs. 261 (210, 355) mg·h/L, Z=2.99, 3.50, respectively; both P<0.05), and the elimination rate constant and clearance rate was lower than those in the control group (0.1 (0.1, 0.2) vs. 0.4 (0.2, 0.5), 0.7 (0.5, 1.3) vs. 2.0 (1.1, 2.8) L/h, Z=2.99, 2.11, respectively; both P<0.05). Conclusion: The PK-PD parameters in septic children treated by ECMO varied with a longer half-life, higher AUC_{0-24 h}, lower elimination rate constant and clearance rate.
Female ; Male ; Humans ; Child ; Child, Preschool ; Infant ; Anti-Bacterial Agents/therapeutic use* ; Vancomycin/therapeutic use* ; Bayes Theorem ; Extracorporeal Membrane Oxygenation ; Prospective Studies ; Sepsis/drug therapy*

Graduate education emphasizes the development of students’ scientific research andinnovation abilities. Literature reading and discussion (LRD) plays an active role in the development ofinnovative thinking and critical thinking for graduate students. However, in traditional, large molecularbiology classes, the effective implementation of large-scale, collective LRD presents a great challenge. Mosoteach is a cloud-based free app designed specifically for education with powerful human-computerinteraction and human-human interaction functions. In the present study, LRD was introduced into amolecular biology course for graduate students and was conducted via the Mosoteach app. The onlinediscussion board in the Mosoteach cloud class was restricted to enrolled students and was designated theprivate online discussion board (PODB). The PODB built a sense of community for students and was aneffective approach for organizing and facilitating discussion in large classes. Small-group learning in LRDwas helpful to understand the literature and foster collaboration and discussion. Overall, we demonstratedthat Mosoteach-based LRD was helpful in improving student learning outcomes. The relationship betweenstudent learning style and engagement, satisfaction and academic performance in cloud classes meritsfurther investigation.

OBJECTIVE: To compare the therapeutic effect of plum-blossom needle tapping at three meridians of wrist combined with rehabilitation training and simple rehabilitation training on wrist joint contracture after stroke. METHODS: A total of 72 patients with wrist joint contracture after stroke were randomized into an observation group and a control group, 36 cases in each one. In the control group, simple rehabilitation training was applied, 5 times a week, 3 weeks as one course and totally 3 courses were required. On the basis of the treatment in the control group, plum-blossom needle tapping at three meridians of wrist was adopted in the observation group. The tapping regions were wrist traveling parts of three meridians of hand, ranging from up 3 to below 1 of wrist crease, 3 times a week, 3 weeks as one course and totally 3 courses were required. The active range of motion (AROM) of active wrist extension, Fugl-Meyer score (FMA) and Barthel index (BI) score were observed before and after treatment in the two groups. RESULTS: The AROM, FMA scores and BI scores after treatment in the two groups were superior to before treatment (<0.05), and the improvements of 3 indexes in the observation group were superior to the control group (<0.05). CONCLUSION The therapeutic effect of plum-blossom needle tapping at three meridians of wrist combined with rehabilitation training is superior to simple rehabilitation training on wrist joint contracture after stroke.
Acupuncture Therapy ; Contracture ; etiology ; therapy ; Humans ; Meridians ; Stroke ; complications ; Stroke Rehabilitation ; Treatment Outcome ; Wrist ; Wrist Joint

To explore the affect and mechanisms of rapamycin on mesangial cell proliferation and cell cycle, rat mesangial cells (HBZY-1) were cultured and divided into the six groups: normal; normal with platelet derived growth factor (PDGF) 20 ng·mL^-1; PDGF + rapamycin 1, 10, 100, 1 000 nmol·L^-1. The cell proliferation was measured by MTT in 24 and 48 h; flow cytometry was used to detect the cell cycle phase. Western blot was performed to determine cyclin D1,cyclin E, cyclin-dependent kinase 2 (CDK2), cyclin-dependent kinase 4 (CDK4), p27, p70S6K/p-p70S6K protein expression. The p27 mRNA was detect by Real-time PCR. The results showed that rapamycin significantly suppressed PDGF induced glomerular mesangial cells (MCs) proliferation in a dose and time-dependent manner, but with the dose increased (1 to 1 000 nmol·L^-1), the time dependence gradually weakened. Rapamycin inhibited mesangial cell proliferation and arrested the cell cycle in the G0/G1 phase. PDGF at 20 ng·mL^-1 significantly increased the expression of cyclin D1, cyclin E and CDK2, CDK4 (P < 0.05), but rapamycin did not affect the expression of cyclin D1, cyclin E and CDK2, CDK4. Rapamycin can significantly inhibited p70S6K phosphorylation, up-regulated the expression of p27 protein and mRNA. Collectively, rapamycin has the effect of inhibiting the glomerular mesangial cells proliferation of mesangial cells by regulating the transcription of p27 mRNA, increasing its protein expression through the mTORC1/p70S6K pathway, resulting in decreased activity of cyclin-CDK, and blocking cell cycle in G0/G1 phase.

Objective: To analyse the clinical history, laboratory tests and pathological data of a patient who suffered from novel coronavirus pneumonia(COVID-19) and provide reference for the clinical treatment of similar cases. Methods: Data of clinical manifestation, laboratory examination, bronchoscopy, echocardiography and cardiopulmonary pathological results were retrospectively reviewed in a case of COVID-19 with rapid exacerbation from mild to critical condition. Results: This patient hospitalized at day 9 post 2019 novel coronavirus(2019-nCoV) infection, experienced progressive deterioration from mild to severe at day 12, severe to critical at day 18 and underwent extracorporeal membrane oxygenation(ECMO) and continuous renal replacement therapy(CRRT) as well as heart lung transplantation during day 28-45 post infection, and died at the second day post heart and lung transplantation. The patient had suffered from hypertension for 8 years. At the early stage of the disease, his symptoms were mild and the inflammatory indices increased and the lymphocyte count decreased continuously. The patient's condition exacerbated rapidly with multi-organ infections, and eventually developed pulmonary hemorrhage and consolidation, pulmonary hypertension, right heart failure, malignant ventricular arrhythmias, liver dysfunction, etc. His clinical manifestations could not be improved despite viral RNAs test results became negative. The patient underwent lung and heart transplantation and finally died of multi organ failure at the second day post lung and heart transplantation. Pathological examination indicated massive mucus, dark red secretions and blood clots in bronchus. The pathological changes were mainly diffused pulmonary hemorrhagic injuries and necrosis, fibrosis, small vessel disease with cardiac edema and lymphocyte infiltration. Conclusions: The clinical course of severe COVID-19 can exacerbate rapidly from mild to critical with lung, liver and heart injuries.
Betacoronavirus ; COVID-19 ; Coronavirus Infections/pathology* ; Fatal Outcome ; Hemorrhage/virology* ; Humans ; Lung/pathology* ; Myocardium/pathology* ; Pandemics ; Pneumonia, Viral/pathology* ; Retrospective Studies ; SARS-CoV-2

The electronic data record system (EDRS) is an useful tool in recording and managing data of clinical trials. The EDRS has characteristics of usability, real-time, high efficiency, error correction, and data manage function. It obviously promotes the efficiency and quality of data record of clinical trials. Meanwhile, as the EDRS is a newly sprouted thing, there are still problems in its stability, data integrity, etc. Here, based on our practical experiences, the applicaiton, usual management, and shortcomings of the EDRS were introduced.

Macrophages are a group of immune cells with pluripotency and plasticity that can differentiate into different phenotypes under different microenvironments in vitro and in vivo. In the development of pulmonary fibrosis, there are alveolar macrophages and interstitial macrophages, which are polarized to different cell phenotypes at different stages of development. And their polarized phenotypes include M1 macrophages and M2 macrophages. In the inflammation early stages of pulmonary fibrosis, the increase of classical activated macrophages are helpful to clear pathogenic microorganisms and promote the progress of inflammation. In the fibrosis stage, the alternatively activated macrophages increased, which inhibiting the inflammatory reaction or directly promoting tissue fibrosis, on the other hand, it also promoting the fibrosis degradation. To clarify the polarization and polarization mechanisms of macrophages in pulmonary fibrosis will be conducive to the treatment of pulmonary fibrosis. In IPF, the polarization mechanism of M1 and M2 is closely related to TGF-β1/Smad. TGF-β1/Smad pathway plays an important regulatory role in liver fibrosis, renal fibrosis, myocardial fibrosis, scars, tumors and other diseases. Blocking the signaling of TGF-β1 by Smad3 and Smad4 is beneficial to inhibit the polarization of AM, which in turn helps to inhibit the progression of IPF.
Fibrosis ; Humans ; Inflammation ; Macrophages ; Pulmonary Fibrosis ; Signal Transduction

To study the evolution of Chinese ancient and modern pharmacopoeia standards and compare the domestic and foreign pharmacopoeias, further understand the international requirements on chrysanthemum quality, and establish a more suitable and modern standard system for high quality Chrysanthemi Flos pieces. Newly Revised Materia Medica, Welfare Pharmacy, Collected Essentials of Species of Materia Medica (Bencao Pinhui Jingyao), Chinese Pharmacopoeia and other herbal remedies in various generations were reviewed to summarize the evolution of domestic standards on Chrysanthemi Flos pieces. Then they were compared with those in European Pharmacopoeia, United States Pharmacopoeia, Japanese Pharmacopoeia and other foreign Pharmacopoeias to establish a modern and international high-quality Chrysanthemi Flos pieces standard system with Chinese medicine characteristics and produce more internationally recognized high-quality Chinese medicine pieces.

Objective To explore the effects of Chinese herbal compound Qinghuayin on the pathological changes of gastric mucosa and interleukin-10 (IL-10) ,nitric oxide (NO) ,gasmn (GAS) and motilin (MTL) in the serum in the animal model of chronic atrophic gastritis (CAG ) in rats .Methods We divided 53 Wistar rats randomly into blank control group (n=8) and CAG model group (n=45) ,and the animal model of CAG in rats was replicated by combination of disease and syndrome .After confirming the sampled rat model was successful built , the other 40 CAG rats in CAG model group were divided into model group ,vitacoenzyme tablet group ,low-dosage TMC group ,medium-dosage TMC group ,and high-dosage TMC group (each group n=8) .With the corresponding drug intervention to different rats for 30 days , the rats were executed . Then their blood was drawn from the abdominal aorta and the gastric tissue was taken to analyze the changes of serum IL-10 ,NO ,GAS and MTL concentrations and gastric mucosa pathology . Results Compared with blank control group , model group had various degrees of gastric mucosa atrophy ; decreased concentrations of serum IL-10 and GAS ; increased NO and MTL ( P<0 .01 ) .Compared with model group,Qinghuayin could improve gastric mucosa pathology in different degrees and increase the concentrations of IL-10 and GAS . Decrease the concentrations of NO and MTL( P<0 .05 or P<0 .01 ) . What's more. The curative effect in high-dosage TMC group was better( P<0. 01 ). Conclusion Chinese herbal compound Qinghuayin can effectively regulate the lopsided expressions of serum IL-10 . NO .GAS and MTL and reverse the pathological and histological changes in the gastric mucosa of CAG rats .

Objective To study the pharmakinetics of 5-methyltetra-hydrofolic acid (5-MTHF) in SD rats by a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS).Methods Six male SD rats weregiven 1.5 × 10-2 mmol · L-1 · kg-1 5-MTHF,and blood was drawn for analysis by HPLC-MS/MS.The plasma was handled by protein precipitation,chromatographic column:Grace Altima HP C18,mobile phases A was methanol-acetonitrile-isopropanol-ethanol-water-formic acid-dimethyl sulphoxide (25∶ 25∶ 25 ∶ 25∶ 0.1 ∶ 1) and mobile phases B was methanol-water-formic acid (10 ∶ 90 ∶ 0.1),gradient elution,flow rate was 0.40 mL · min-1 The method validation was conducted by investigating linear range,accuracy and precision,stability,recovery and matrix effects.The pharmacokinetic parameters were calculated by WinNonlin.Results The method had a linear range of 10.00-1.00 × 104 ng · mL-1 with good correlation,and the regression equation was y =1.01 × 10-3x + 1.82 × 10-3(r =0.998 3).The intra-day and inter-day accuracy and precision,the recovery,the matrix effects,and the stability were also validated and met the requirement.Pharmacokinetic parameters:the t1/2was (15.23 ± 5.76)h,and AUC0-t was (2788.52 ± 348.86)ng· mL-1 · h without baseline 5-MTHF concentration deduction;the t1/2 was (1.57 ±0.34)h,and AUC0-t was (971.80 ±237.58)ng · mL-1 · h with deduction of the baseline 5-MTHF concentration.Conclusion A sensitive and accurate HPLC-MS/MS method was developed for the determination of 5-MTHF.