Osteoporosis is a common bone disease， whose incidence is still on the rise， posing great challenges to patients and society. This review mainly studies the pathogenesis of osteoporosis from the aspects of oxidative stress， inflammatory response， and glucolipotoxicity-induced injury and clarifies the efficacy and mechanism of some active ingredients of traditional Chinese medicine against osteoporosis through the integration of in vitro and in vivo experiments. The experimental results suggest that some active ingredients can improve bone resorption markers and maintain bone homeostasis by modulating inflammation， oxidative stress， etc. These active ingredients regulate osteoporosis through the receptor activator of nuclear transcription factor-κB （NF-κB） ligand （RANKL） pathway， osteoprotegerin （OPG） pathway， Wnt/β-catenin pathway， NF-κB pathway， mitogen-activated protein kinase （MAPK） pathway， adenosine monophosphate （AMP）-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） pathway， and oxidative stress pathway. This review provides ideas for the progress of the prevention and treatment of osteoporosis with the active ingredients of traditional Chinese medicine， aiming to provide new potential lead compounds and reference for the development of innovative drugs and clinical therapy for the treatment of osteoporosis.

Objective:To establish standard spatial brain template and ROIs template of 11C-methyl- N-2β-carbomethoxy-3β-(4-fluorophenyl)tropane (CFT) PET images for automated quantitative analysis of dopamine transporter (DAT) distribution. Methods:From May 2014 to December 2015, 11C-CFT PET and MRI T 1 brain images of 16 healthy volunteers (3 males, 13 females; age (63.3±6.9) years) from Huashan Hospital, Fudan University were co-registered and smoothed using statistical parametric mapping(SPM)5 software based on MATLAB to create a standard spatial brain template. The ROIs template was established by ScAnVp procedures. These templates were clinically verified by using 11C-CFT PET images of 37 healthy volunteers (23 males, 14 females; age (61.7±7.1) years), 32 Parkinson′s disease (PD) patients (20 males, 12 females; age (61.1±5.4) years), 10 multiple system atrophy with predominant parkinsonism (MSA-P) patients (7 males, 3 females; age (60.8±7.1) years) and 10 progressive supranuclear palsy (PSP) patients (5 males, 5 females; age (58.4±6.1) years) from Huashan Hospital, Fudan University between January 2014 and March 2019. One-way analysis of variance was used to analyze data. Results:Based on the 11C-CFT PET images and MRI T 1 images of healthy volunteers, a standard spatial brain template for normalization of 11C-CFT PET images was created. The ROIs template was established including seven regions: bilateral caudate, anterior putamen, posterior putamen (along the long axis) and the occipital cortex. The ROIs template was accurately aligned in each verification group. The normal reference values of semi-quantitative DAT distribution in caudate, anterior putamen and posterior putamen were obtained (1.84±0.13, 2.18±0.16, 1.77±0.11). The semi-quantitative values of 11C-CFT uptake in each ROI in patients were significantly lower than those in healthy volunteers ( F values: 49.79-283.83, all P<0.05). Conclusion:The established brain templates with accurate spatial alignment for 11C-CFT image analysis can provide foundational tools for the application of 11C-CFT PET imaging in clinical practice and scientific research.

Objective:To investigate the effect of inferior vena cava variability (IVCV) combined with difference of central venous-to-arterial partial pressure of carbon dioxide (Pcv-aCO 2) on guiding fluid resuscitation in septic shock. Methods:Patients with septic shock admitted to the department of critical care medicine of Jiangxi Provincial People's Hospital from January 1, 2018 to December 31, 2020 were enrolled, and they were divided into control group and observation group according to random number table method. Patients in both groups were given fluid resuscitation according to septic shock fluid resuscitation guidelines. The patients in the control group received fluid resuscitation strictly according to the early goal-directed therapy (EGDT) strategy. Resuscitation target: central venous pressure (CVP) 12-15 cmH 2O (1 cmH 2O≈0.098 kPa), mean arterial pressure (MAP) > 65 mmHg (1 mmHg≈0.133 kPa), mean urine volume (UO) > 0.5 mL·kg -1·h -1, central venous oxygen saturation (ScvO 2) > 0.70. In the observation group, the endpoint of resuscitation was evaluated by IVCV dynamically monitored by bedside ultrasound and Pcv-aCO 2. Resuscitation target: fixed filling of inferior vena cava with diameter > 2 cm, IVCV < 18%, and Pcv-aCO 2 < 6 mmHg. The changes in recovery indexes before and 6 hours and 24 hours of resuscitation of the two groups were recorded, and the 6-hour efficiency of fluid resuscitation, 6-hour lactate clearance rate (LCR) and 6-hour and 24-hour total volume of resuscitation were also recorded; at the same time, the duration of mechanical ventilation, length of intensive care unit (ICU) stay, 28-day mortality and the incidence of acute renal failure and acute pulmonary edema between the two groups were compared. Results:A total of 80 patients were enrolled in the analysis, with 40 in the control group and 40 in the observation group. The MAP, CVP and ScvO 2 at 6 hours and 24 hours of resuscitation in the two groups were significantly higher than those before resuscitation, while Pcv-aCO 2 and blood lactic acid (Lac) were significantly decreased, and UO was increased gradually with the extension of resuscitation time, indicating that both resuscitation endpoint evaluation schemes could alleviate the shock state of patients. Compared with before resuscitation, IVCV at 6 hours and 24 hours of resuscitation in the observation group were decreased significantly [(17.54±4.52)%, (18.32±3.64)% vs. (27.49±10.56)%, both P < 0.05]. Compared with the control group, MAP and ScvO 2 at 6 hours of resuscitation in the observation group were significantly increased [MAP (mmHg): 69.09±4.64 vs. 66.37±4.32, ScvO 2: 0.666±0.033 vs. 0.645±0.035, both P < 0.05], 24-hour MAP was increased significantly (mmHg: 75.16±3.28 vs. 70.12±2.18, P < 0.05), but CVP was relatively lowered (cmH 2O: 9.25±1.49 vs. 10.25±1.05, P < 0.05), indicating that the fluid resuscitation efficiency was higher in the observation group. Compared with the control group, 6-hour LCR in the observation group was significantly increased [(55.64±6.23)% vs. (52.45±4.52)%, P < 0.05], 6-hour and 24-hour total volume of resuscitation was significantly decreased (mL: 2 860.73±658.32 vs. 3 568.54±856.43, 4 768.65±1 085.65 vs. 5 385.34±1 354.83, both P < 0.05), the duration of mechanical ventilation was significantly shortened (days: 6.78±3.45 vs. 8.45±2.85, P < 0.05), while the incidence of acute pulmonary edema was significantly decreased [2.5% (1/40) vs. 20.0% (8/40), P < 0.05]. There was no significant difference in the length of ICU stay, 28-day mortality or incidence of acute renal failure between the two groups. Conclusions:Dynamic monitoring of IVCV and Pcv-aCO 2 can effectively guide the early fluid resuscitation of patients with septic shock, and compared with EGDT, it can significantly shorten the duration of mechanical ventilation, reduce the amount of fluid resuscitation, and reduce the incidence of acute pulmonary edema. Combined with its non-invasive characteristics, it has certain clinical advantages.

ObjectiveTo analyze the drop-out rate of participants in antidepressant clinical trials and to explore the related influencing factors. MethodsA retrospective analysis was carried out on the participants of 9 antidepressant clinical trials conducted at the Affiliated Brain Hospital of Guangzhou Medical University from 2013 to 2020. A self-compiled questionnaire was used to collect the subjects' demographic data， disease characteristics and the final completion of the trial， thereafter， the participant drop-out rate and related influencing factors were discussed. ResultsA total of 157 cases were enrolled， including 120 cases completed and 37 cases dropped out the trail. The causes of drop-out were poor efficacy in 13 cases （35.14%）， presence of adverse reactions in 12 cases （32.43%）， withdrawal of informed consent in 8 cases （21.62%） and loss of follow-up in 4 cases （10.81%）. Correlation analysis showed that participant drop-out was positively correlated with the level of anxiety （r=0.224， P<0.01） and presence of adverse events （r=0.158， P<0.05）， meantime， negatively correlated with the level of education （r=-0.209， P<0.01） and overall efficacy （r=-0.545， P<0.01）. Binary Logistic regression analysis showed that education level （β=-0.611， OR=0.543， P<0.05）， number of visits （β=-1.831， OR=0.160， P<0.01） and overall efficacy （β=-2.286， OR=0.102， P<0.01） were the influencing factors of participant drop-out. ConclusionLow education level， first visit， poor outcome， high level of anxiety， and adverse events are the factors affecting participant drop-out in antidepressant clinical trials.

Objective:To investigate the protective effect and mechanism of celastrol in acute lung injury (ALI) of septic rats.Methods:According to random number table, 24 male Sprague-Dawley (SD) rats were divided into control group (Con group), Sham operation group (Sham group), sepsis-induced ALI group by cecal ligation and perforation (CLP group) and celastrol intervention group (CLP+celastrol group, 2 mg/kg intraperitoneal administration 1 hour before surgery), 6 rats in each group. The abdominal aortic blood of the rats was collected for blood gas analysis 24 hours after the surgery, and then the rats were sacrificed and the lung tissues were taken to calculate the lung wet/dry weight ratio (W/D). The pathological characteristics of lung tissues were observed under light microscope and calculated the lung injury score. The protein levels of Toll-like receptor 4 (TLR4), interleukins (IL-6, IL-10), and nuclear factor-κB (NF-κB) of cytoplasm and nucleus in lung tissues were detected by enzyme linked immunosorbent assay (ELISA).Results:The partial arterial oxygen pressure (PaO 2), lung W/D ratio, lung injury score and the protein levels of inflammatory factor in lung tissues had no differences between Con group and Sham group. Compared with the Con group, PaO 2 in the CLP group was significantly decreased [mmHg (1 mmHg = 0.133 kPa): 60.33±2.01 vs. 109.20±2.99], the lung W/D ratio and lung injury score were significantly increased (lung W/D ratio: 4.44±0.05 vs. 3.27±0.04, lung injury score: 10.67±0.42 vs. 0.50±0.22), and the protein levels of TLR4, IL-6, IL-10 and the nucleus NF-κB in the lung tissues were significantly increased [TLR4 (pg/L): 21.87±0.66 vs. 3.27±0.09, IL-6 (ng/L): 861.10±8.28 vs. 120.30±3.91, IL-10 (ng/L): 212.40±2.57 vs. 41.73±1.02, nuclear NF-κB (ng/L): 707.70±16.82 vs. 403.30±7.46], but the protein level of cytoplasm NF-κB was significantly decreased (ng/L: 213.70±8.67 vs. 408.30±8.71), with statistically significant differences (all P < 0.05). Compared with the CLP group, PaO 2 in CLP+celastrol group was significantly increased (mmHg: 76.83±3.21 vs. 60.33±2.01), the lung W/D ratio and lung injury score were significantly decreased (lung W/D ratio: 3.82±0.03 vs. 4.44±0.05, lung injury score: 5.00±0.37 vs. 10.67±0.42), and the protein levels of TLR4, IL-6, IL-10 and nucleus NF-κB in the lung tissue were significantly decreased [TLR4 (pg/L): 7.57±0.21 vs. 21.87±0.66, IL-6 (ng/L): 380.90±6.55 vs. 861.10±8.28, nuclear NF-κB (ng/L): 533.80±9.42 vs. 707.70±16.82], and the protein level of cytoplasm NF-κB was significantly increased (ng/L: 342.70±14.96 vs. 213.70±8.67), with statistically significant differences (all P < 0.05), while the protein level of IL-10 in lung tissues had no significant difference (ng/L: 210.50±3.16 vs. 212.40±2.57, P > 0.05). Conclusion:Celastrol may regulate the expression and release of inflammatory factors by inhibiting the TLR4/NF-κB pathway, thereby alleviating the ALI induced by sepsis in rats.

Objective:To evaluate the effect of airway driving pressure (ΔP) guided sedation strategy on the prognosis of patients with mechanical ventilation.Methods:Patients who needed invasive mechanical ventilation and admitted to the department of intensive care unit (ICU) of Jiangxi Provincial People's Hospital from January 2017 to December 2018 were enrolled. The patients were divided into study group and control group according to the random number table. After informed consent of patients or their families, both groups received routine treatment in ICU. The control group was treated with light sedation strategy, the Richmond agitation sedation score (RASS) was performed every 4 hours, and the target was RASS > -3. ΔP in the study group was measured once a day, and the sedative target of patients with low driving pressure (ΔP ≤ 14 cmH 2O, 1 cmH 2O = 0.098 kPa) was RASS > -3, while the patients with high driving pressure (ΔP > 14 cmH 2O) was RASS ≤ -3. The evaluation was conducted at 28 days after admission to ICU, and the patients were followed up to 60 days. The main outcome was days without mechanical ventilation in 28 days. The secondary outcomes were the rate of extubation, discharge outcome, incidence of ventilator associated pneumonia (VAP) and delirium, and 60-day survival rate. Results:A total of 60 patients with respiratory failure due to various reasons were recruited, 30 in each group. There was no significant difference in gender, age, primary disease, severity of disease or ΔP between the two groups. The days without mechanical ventilation within 28 days in the study group were significantly more than that in the control group [days: 20 (0, 23) vs. 12 (0, 16), P = 0.018], and the incidences of VAP (3.3% vs. 16.7%, P = 0.045) and delirium (0% vs. 10.0%, P = 0.038) were significantly lower than that in the control group. There were no significant differences in the rate of extubation (73.3% vs. 66.7%, P = 0.273), discharge outcome [improvement (cases): 24 vs. 21, unhealed (cases): 2 vs. 5, deaths (cases): 4 vs. 4, P = 0.506] and 60-day survival rate (83.3% vs. 76.7%, P = 0.519) between the study group and control group. Conclusion:Compared with light sedation strategy, ΔP directed sedation strategy can effectively shorten the duration of mechanical ventilation and reduce the incidence of VAP and delirium in the ICU patients.

Objective To study the effect of short-term treatment of subthalamic nucleus ( STN ) deep brain stimulation (DBS) on cerebral glucose metabolism in patients with Parkinson's disease (PD) and its relationship with the change of brain motor-related nerve pathways. Methods Five patients ( 2 males, 3 females;age:(63.6±11.8) years) with PD who underwent STN DBS between January 2014 and December 2018 were enrolled in this study. All patients underwent 18F-fluorodeoxyglucose (FDG) PET in "DBS-off"state before and 3 months after operation. Quantitative expression of PD-related metabolic pattern (PDRP) were calculated by scaled subprofile model/principal component analysis ( SSM/PCA) on PET images. Brain regions with changes of glucose metabolism after DBS were located by statistical parametric mapping (SPM) paired t test. Results Compared with pre-operation, PDRP expression (5.1±1.3 vs 2.9±1.8) and unified Parkinson's disease rating scale (UPDRS) motor score (50.2±8.2 vs 28.0±5.4) of PD patients were significantly decreased 3 months after STN DBS (t values:6.17 and 3.88, both P<0.05). After DBS, the glucose metabolism of bilateral globus pallidus/putamen, caudate nucleus, thalamus, insula, pons and cer-ebellum decreased, while the glucose metabolism of bilateral prefrontal motor area and parietooccipital lobe increased ( t=3.75, P<0.01) . Conclusions Short-term STN DBS therapy can inhibit the cortico-striatum-pallidum-hypothalamus-cortex motor loop, which is abnormally excitable in the brain of PD. PDRP, as an imaging characterization of the regulation of this loop, is expected to become an imaging marker for monito-ring the treatment of PD.

Objective: To study the effect of short-term treatment of subthalamic nucleus (STN) deep brain stimulation (DBS) on cerebral glucose metabolism in patients with Parkinson′s disease (PD) and its relationship with the change of brain motor-related nerve pathways. Methods: Five patients (2 males, 3 females; age: (63.6±11.8) years) with PD who underwent STN DBS between January 2014 and December 2018 were enrolled in this study. All patients underwent ¹⁸F-fluorodeoxyglucose (FDG) PET in " DBS-off" state before and 3 months after operation. Quantitative expression of PD-related metabolic pattern (PDRP) were calculated by scaled subprofile model/principal component analysis (SSM/PCA) on PET images. Brain regions with changes of glucose metabolism after DBS were located by statistical parametric mapping (SPM) paired t test. Results: Compared with pre-operation, PDRP expression (5.1±1.3 vs 2.9±1.8) and unified Parkinson′s disease rating scale (UPDRS) motor score (50.2±8.2 vs 28.0±5.4) of PD patients were significantly decreased 3 months after STN DBS (t values: 6.17 and 3.88, both P<0.05). After DBS, the glucose metabolism of bilateral globus pallidus/putamen, caudate nucleus, thalamus, insula, pons and cerebellum decreased, while the glucose metabolism of bilateral prefrontal motor area and parietooccipital lobe increased (t=3.75, P<0.01). Conclusions Short-term STN DBS therapy can inhibit the cortico-striatum-pallidum-hypothalamus-cortex motor loop, which is abnormally excitable in the brain of PD. PDRP, as an imaging characterization of the regulation of this loop, is expected to become an imaging marker for monitoring the treatment of PD.

OBJECTIVE： To establish a method for simultaneous determination of matrine， oxymatrine， gallic acid， peoniflorin， costunolide and dehydrocostus lactone in Libiling tablets. METHODS： RP-HPLC method was adopted. The determination was performed on Agilent ZORBAX SB-C18 column with mobile phase consisted of methanol-0.1％ phosphoric acid （gradient elution） at the flow rate of 1.0 mL/min. The detection wavelengths were 210 nm （matrine， oxymatrine） and 225 nm （gallic acid， peoniflorin， costunolide， dehydrocostus lactone）. The column temperature was set at 30 ℃， and sample size was 5 μL. RESULTS： The linear ranges of matrine， oxymatrine， gallic acid， peoniflorin， costunolide， dehydrocostus lactone were 0.053-5.28 mg/mL（r＝0.999 8）， 0.125-12.54 mg/mL（r＝0.999 9）， 0.013-1.33 mg/mL（r＝0.999 8）， 0.169-16.94   mg/mL（r＝0.999 9）， 0.048-4.77 mg/mL（r＝0.999 8）， 0.072-7.16 mg/mL （r＝0.999 9）. The limits of quantitation were 4.08×10－4， 4.48×10－4， 3.12×10－4， 2.10×10－4， 1.36×10－4， 1.84×10－4 mg/mL， respectively. The limits of detection were 1.24×10－4， 1.50×10－4， 1.02×10－4， 6.20×10－5， 4.20×10－5， 6.40×10－5 mg/mL， respectively. RSDs of precision， stability and reproducibility tests were all lower than 2％ （n＝6）. The recoveries were 98.03％-101.43％ （RSD＝1.25％， n＝6）， 97.73％-102.26％ （RSD＝1.96％， n＝6）， 97.18％-101.41％ （RSD＝1.98％，n＝6）， 97.45％-102.11％ （RSD＝1.88％，n＝6）， 96.85％-101.07％ （RSD＝1.75％， n＝6）， 97.12％-102.64％ （RSD＝1.82％，n＝6）， respectively. CONCLUSIONS： Established method is simple， stable and rapid， and can be used for simultaneous determination of 6 components in Libiling tablets.

Objective To investigate the correlation between plasma homocysteine(Hcy)level and lower extremity atherosclerotic disease(LEAD)in elderly patients of Chinese Han nationality with primary hypertension.Methods A total of 144 elderly Chinese Han outpatients with primary hypertension aged 60-90 years (92 cases in men,52 in women)were randomly recruited in our department from January 2015 to January 2017.The diagnosis of LEAD was confirmed in this study by ankle brachial index(ABI)≤0.90(ABI normal value=1.00-1.40).The patients were divided into three different plasma Hcy level groups:low-(＜ 10 μmol/L),middle-(10-29 μmol/L),and high-Hcy level group(≥30 μmol/L).The differences in Hcy,ABI,toe branchial index,high density lipoprotein,apolipoprotein-A1,and baPWV were compared between three different Hcy level groups.Pearson correlation was established between the influencing factors and serum level of Hcy.Moreover,binary logistic regression model was used to determine the independent risk factors for LEAD among elderly Chinese Han patients with primary hypertension.Results The values of apolipoprotein A-1,high density lipoprotein cholesterol,ankle brachial index,and toe brachial index were higher in the low Hcy group than in the middle-and high Hcy-group(P＜0.05).The ankle brachial index was higher in the middle Hcy group than in the high Hcy group(P＜0.05).The brachial-ankle pulse wave velocity was higher in the high Hcy group than in the middle and low Hcy group (P ＜ 0.05).No statistically significant difference was found in age,gender,body mass index,mean arterial pressure,triglyceride,low density lipoprotein cholesterol,blood urea nitrogen,serum creatinine,blood uric acid,and plasma hypersensitivity C-reactive protein among the three groups(all P＞0.05).Pearson correlation analysis showed that the level of serum Hcy was positively correlated with brachial-ankle pulse wave velocity (r=0.637,P =0.000),while it was negatively correlated with ankle brachial index,toe branchial index,high density lipoprotein cholesterol,and apolipoprotein A-1 (r =-0.743,-0.257,-0.240,-0.449,all P＜0.05).Binary Logistic regression model showed that gender,Hcy,and low density lipoprotein cholesterol level were independent risk factors for LEAD in elderly Chinese Han patients with primary hypertension.Conclusions Plasma Hcy level is an independent risk factor for LEAD in elderly Chinese Han patients with primary hypertension,and it is positively correlated with this disease.