OBJECTIVE To establish a population pharmacokinetic(PopPK)model to predict the PK characteristics of GLS-010 in humans.METHODS Fifty-eight cynomolgus monkeys were used,18 of which were randomly divided into three groups and received a single intravenous infusion of GLS-010 at doses of 2,6,and 18 mg·kg-1,respectively.The rest were randomly assigned to four groups and received multiple intravenous infusions of GLS-010 at doses of 0,5,25,and 100 mg·kg-1,respectively,once a week(quaque week,qw)for five consecutive weeks.Blood samples were collected before and after administration.The concentrations of GLS-010 in the monkey serum were measured using a validated enzyme-linked immunosorbent assay,while those of anti-drug antibodies(ADA)in the cynomolgus monkey serum were determined by ultra-sensitive electrochemiluminescence immunoassay.The PK data on GLS-010 in cynomolgus monkeys was obtained,and the drug-time curves were plotted.A PopPK model was constructed using non-compartmental analysis and evaluated by goodness-of-fit plots and visual predictive checks.The constructed PopPK model was used to predict the PK characteristics in humans,which were finally compared with actual Phase Ⅰ clinical study results for validation.RESULTS The predictive results of the PopPK model were highly consistent with the actual Phase Ⅰ clinical study results.The model was able to predict the human PK characteristics under various dosing regimens,including 1 mg·kg-1 quaque 2 weeks(q2w),4 mg·kg-1(q2w),240 mg(q2w),240 mg(q3w),and 10 mg·kg-1(q2w).The predicted maximum plasma concentrations(Cmax)were 24.8,99.1,85.0,85.0,and 247.8 mg·L-1,respectively,and the AUC0-336h was 4 902.0,20 060.0,17 147.7,22 145.7(AUC0-504h),and 50 817.6 mg·h·L-1,respectively.The safety risks for the corresponding dosing regimens were 47.3,11.6,13.5,10.5,and 4.6,respectively.The predicted receptor occupancy at steady state(ROss)at Cmax,average plasma concentration(Cavg),and minimum plasma concentration(Cmin)were 38.8％,72.7％,69.4％,64.1％and 87.2％,29.1％,63.8％,60.0％,49.8％and 82.1％,21.9％,55.5％,51.3％,36.3％and 76.7％,respectively.CONCLUSION The PopPK model can effectively predict the human PK characteristics under different dosing regimens with high consistency with actual Phase Ⅰ clinical study results,which can serve as an important reference for selection of safe and effective doses for first-in-human research.

OBJECTIVE To establish a population pharmacokinetic(PopPK)model to predict the PK characteristics of GLS-010 in humans.METHODS Fifty-eight cynomolgus monkeys were used,18 of which were randomly divided into three groups and received a single intravenous infusion of GLS-010 at doses of 2,6,and 18 mg·kg-1,respectively.The rest were randomly assigned to four groups and received multiple intravenous infusions of GLS-010 at doses of 0,5,25,and 100 mg·kg-1,respectively,once a week(quaque week,qw)for five consecutive weeks.Blood samples were collected before and after administration.The concentrations of GLS-010 in the monkey serum were measured using a validated enzyme-linked immunosorbent assay,while those of anti-drug antibodies(ADA)in the cynomolgus monkey serum were determined by ultra-sensitive electrochemiluminescence immunoassay.The PK data on GLS-010 in cynomolgus monkeys was obtained,and the drug-time curves were plotted.A PopPK model was constructed using non-compartmental analysis and evaluated by goodness-of-fit plots and visual predictive checks.The constructed PopPK model was used to predict the PK characteristics in humans,which were finally compared with actual Phase Ⅰ clinical study results for validation.RESULTS The predictive results of the PopPK model were highly consistent with the actual Phase Ⅰ clinical study results.The model was able to predict the human PK characteristics under various dosing regimens,including 1 mg·kg-1 quaque 2 weeks(q2w),4 mg·kg-1(q2w),240 mg(q2w),240 mg(q3w),and 10 mg·kg-1(q2w).The predicted maximum plasma concentrations(Cmax)were 24.8,99.1,85.0,85.0,and 247.8 mg·L-1,respectively,and the AUC0-336h was 4 902.0,20 060.0,17 147.7,22 145.7(AUC0-504h),and 50 817.6 mg·h·L-1,respectively.The safety risks for the corresponding dosing regimens were 47.3,11.6,13.5,10.5,and 4.6,respectively.The predicted receptor occupancy at steady state(ROss)at Cmax,average plasma concentration(Cavg),and minimum plasma concentration(Cmin)were 38.8％,72.7％,69.4％,64.1％and 87.2％,29.1％,63.8％,60.0％,49.8％and 82.1％,21.9％,55.5％,51.3％,36.3％and 76.7％,respectively.CONCLUSION The PopPK model can effectively predict the human PK characteristics under different dosing regimens with high consistency with actual Phase Ⅰ clinical study results,which can serve as an important reference for selection of safe and effective doses for first-in-human research.

Objective:To analyze the clinical features and laboratory indicators in patients with solid malignant tumor-associated venous thromboembolism(Ta-VTE),and to study the risk factors for Ta-VTE.Methods:The hospitalized patients with VTE in Guizhou Provincial People's Hospital from January to December 2020 were enrolled,and they were divided into Ta-VTE group and pure VTE group based on the presence or absence of solid malignant tumor.The differences in clinical data and laboratory indicators between the two groups were analyzed,and the indicators with significant differences were included in logistic regression model to analyze the risk factors of Ta-VTE.Results:A total of 288 patients with VTE were included in this study,including 64 cases in Ta-VTE group and 224 cases in pure VTE group,respectively.There were significant differences in the following indexes between the two groups,including the hospitalization time(14.20±15.29 d vs 10.05±6.90 d,t=3.112,P=0.002),pain(35.94％vs 65.18％,x2=17.554,P=0.000),recent surgery(75.00％vs 37.50％,X2=28.196,P=0.000),D-dimer[2.8(0.92,7.55)μg/ml vs 5.69(2.25,13.91)μg/ml,Z=-2.710,P=0.007],PLR[198.59(139.54,312.16)vs 149.76(114.08,233.66),Z=-2.924,P=0.003]and TBIL[10.90(7.63,15.68)μmol/Lvs 12.90(9.33,18.28)μmol/L,Z=-2.066,P=0.039].There was no significant difference in the other indicators(P＞0.05).The result of multivariate logistic regression analysis showed that elevated PLR(OR=1.003,95％CI:1.000-1.006,P=0.027),recent surgery(OR=4.312,95％CI:2.093-8.885,P=0.000)and prolonged hospitalization(OR=1.037,95％CI:1.002-1.074,P=0.038)were independent risk factors for Ta-VTE.However,pain(OR=0.274,95％CI:0.133-0.564,P=0.000)was a protective factor.Conclusion:Elevated PLR level,recent surgery and prolonged hospital stay are independent risk factors for Ta-VTE patients,and rational use of these indicators is helpful for the clinical diagnosis and treatment of Ta-VTE patients.

OBJECTIVE: To retrospectively study medium term follow up outcomes effects of effect of bio-lengthend stem hemiarthroplasty in the treatment of unstable osteoporotic intertrochanteric fractures in elderly patients. METHODS: Total of 32 elderly patients with the osteoporotic intertrochanteric fractures were treated with bio-lengthend stem hemiarthroplasty from Jan. 2016 to Jan. 2019 including 14 males and 22 females, aged from 85 to 95 years old with an average of (89.5±4.5) years old. According to classification of Evans, there were 12 cases with type Ⅲ, 11 with type Ⅳ and 9 with type Ⅳ. The time from injury to operation ranged from 0.5 to 9 days with an average of (4.5±3.9) days. The operation time, blood loss and postoperative complications were analyzed. Functional outcome was assessed by Parker Palmer mobility score(PPMS) and Harris hip score. RESULTS: Four patients died within one year after operation, and the mortality was 12.5%. The follow up time for the rest 28 patients ranged from 24 to 60 months with an average of (28.5±4.5) months. The mean operative time was (54.2±22.5) min;the mean blood loss (hidden blood loss+obvious blood loss) was (450±140) ml;the first weight bearing was (3.35±1.35) days. No perioperative death occurred. PPMS were(6.63±1.25), (6.94±1.18), (7.11±0.83), (7.32±1.11) and Harris scores were(67.85±6.19), (71.42±5.57), (73.41±5.62), (77.32±5.24) respectively at 1, 3, 6 months and the final follow-up after operation. There were no significant difference in PPMS and Harris score at 1, 3, 6 months after operation and the final follow-up(P>0.05). There were no complications such as joint dislocation and prosthesis loosening occure at the final follow-up. CONCLUSION On the premise of strictly mastering the case selection criteria, the bio-lengthend stem hemiarthroplasty in the treatment of unstable osteoporotic intertrochanteric fractures in elderly patients has a satisfied medium term follow-up outcomes. It can restore hip function in the early stage and improve the quality of life of patients.
Male ; Female ; Humans ; Aged ; Aged, 80 and over ; Arthroplasty, Replacement, Hip ; Hemiarthroplasty ; Quality of Life ; Retrospective Studies ; Treatment Outcome ; Hip Fractures/surgery* ; Osteoporotic Fractures/surgery*

Objective:To evaluate the hemostatic effects of our self-designed pelvic band with inflatable balloon in a swine model of hemodynamically unstable pelvic fracture.Methods:"Open-book like" fractures were created with the external iliac blood vessels exposed in 24 12-month-old female Bama miniature pigs which were randomly divided into 4 groups ( n=6). Group C (the control group) was subjected to no treatment other than exposure of the external iliac blood vessels, group D to no treatment following destruction of the external iliac blood vessels, group T1 to fixation with simple pelvic band after destruction of the external iliac blood vessels, and group T2 to fixation with our self-designed pelvic band with inflatable balloon after destruction of the external iliac blood vessels. The 4 groups were compared in terms of 40-min survival rate, bladder pressure, peak lactate value, total blood loss, bleeding rate, infusion rate, and angiographic images. Results:There was no significant difference in the baseline indexes among the 4 groups before experiment, showing comparability ( P>0.05). The 40-min survival rate in group T2 was 83.3% (5/6), significantly higher than that in groups D and T1 [0% (0/6) and 0% (0/6)] ( P<0.05). There were no significant differences among groups C, D, T1 and T2 in bladder pressure [(6.67±1.03) mmHg, (5.83±1.94) mmHg, (6.00±1.55) mmHg, and (6.00±1.10) mmHg] or in total blood loss among groups D, T1 and T2[(1,198.0±182.9) mL, (1,252.0±148.4) mL, and (1,150.0±125.7) mL] (all P>0.05). The peak lactate value in group T2 [(2.26±0.24) mmol/L] was significantly lower than that in group D [(5.00±0.60) mmol/L] and group T1 [(3.86±0.57) mmol/L], and the bleeding rate and infusion rate in group T2 [(25.83±5.49) mL/min and (26.00±4.69) mL/min] were also significantly lower than those in group D [(83.50±19.85) mL/min and (71.50±29.11) mL/min] and group T1 [(54.17±15.59) mL/min and (54.17±8.98) mL/min] (all P<0.05). Angiography showed contrast agent extravasation in group T2, especially from the artery, but the extravasation speed in group T2 was significantly slower than that in group D. Conclusion:In a swine model of hemodynamically unstable pelvic fracture, our self-designed pelvic band with inflatable balloon has a definite hemostatic effect on vascular injury which is better than that of a simple pelvic band.

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

OBJECTIVE: To systematically evaluate the efficacy and safety of conventional therapy combined with moxibustion in the treatment of chronic obstructive pulmonary disease (COPD) in stable phase based on Meta-analysis medicine. METHODS: The randomized controlled trials (RCTs) of moxibustion as adjuvant therapy for COPD were retrieved from the databases of CNKI, Wanfang, SinoMed, PubMed, Web of Science, Cochrane Library and Ebsco. RevMan5.3 software was used for Meta analysis, and the quality of evidence was evaluated according to GRADE standards. RESULTS: A total of 16 RCTs were included, involving 1425 patients. The results of Meta-analysis showed that: compared with the conventional treatment, ①the adjuvant therapy with moxibustion had advantages in reducing the number of acute exacerbations [ CONCLUSION The efficacy of moxibustion as adjuvant therapy for COPD in stable phase is better than that of simple conventional therapy. Due to insufficient clinical evidence and the limitations of this study, clinical safety is unclear and further evidence is needed to support the results.
Humans ; Lung ; Moxibustion ; Pulmonary Disease, Chronic Obstructive/therapy* ; Treatment Outcome

"The Expert Group on Tumor Ablation Therapy of Chinese Medical Doctor Association, The Tumor Ablation Committee of Chinese College of Interventionalists, The Society of Tumor Ablation Therapy of Chinese Anti-Cancer Association and The Ablation Expert Committee of the Chinese Society of Clinical Oncology" have organized multidisciplinary experts to formulate the consensus for thermal ablation of pulmonary subsolid nodules or ground-glass nodule (GGN). The expert consensus reviews current literatures and provides clinical practices for thermal ablation of GGN. The main contents include: (1) clinical evaluation of GGN, (2) procedures, indications, contraindications, outcomes evaluation and related complications of thermal ablation for GGN and (3) future development directions.
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Objective: To observe the effect of Yi Jin Jing (Sinew-transforming Qigong Exercises) on the muscle strength in senile sarcopenia. Methods: Sixty-five old people with sarcopenia were randomized into Yi Jin Jing group and a blank control group. Thirty-three patients in Yi Jin Jing group practiced Yi Jin Jing (Sinew-transforming Qigong Exercises), while 32 patients in the blank control group didn't receive any interventions. The muscle strength was measured before and after 12-week training. Results: During the study, each group had 1 dropout. The muscle strength was improved after 12-week training in Yi Jin Jing group, and the difference was statistically significant (P<0.05); there was no significant difference in the blank control group (P>0.05). After the intervention, there was a significant difference between Yi Jin Jing group and the blank control group in comparing the muscle strength (P<0.05). Conclusion: Constant Yi Jin Jing (Sinew-transforming Qigong Exercises) training can notably improve skeletal muscle strength in senile sarcopenia.

Objective To study the bibenzyls and phenanthrenes from Arundina graminifolia.Methods The compounds were extracted by 95％ alcohol and isolated by column chromatography on silica gel and Sephadex LH-20.Their structures were identified by spectroscopic analysis (1H NMR and13CNMR).Results Eleven compouds were obtained and identified as batatasin Ⅲ (1),arundinanin (2),2,8-dihydroxy-4,7-dimethoxy-9,10-dihydrophenanthrene (3),shancidin (4),arundinan (5),isoshancidin (6),erianthridin (7),lusianthridin (8),eulophiol (9),flavanthrin (10),orchinol (11).Conclusion Compounds 3,7,9 were isolated from this plant for the first time.