Phytochemical investigation on the ethanol extract of a well-known medicinal herb Leonurus japonicus, led to the separation of 18 labdane type diterpenoids (1-18). Through comprehensive spectroscopic analyses and quantum chemical calculations, these compounds were structurally characterized as six new interesting 5,5,5-di-spirocyclic ones (1-6), two new (7 and 8) and six known (13-18) interesting 6,5,5-di-spirocyclic ones, a new rare 14,15-dinor derivative (9), and three new ones incorporating a γ-lactone unit (10-12). An in vitro neuroprotective assay in RSC96 cells revealed that compounds 7 and 12 exhibited neuroprotective activity in a concentration-dependent way, comparable to the reference drug N-acetylcysteine.
Magnetic Resonance Spectroscopy ; Leonurus/chemistry* ; Plants, Medicinal ; Diterpenes/chemistry* ; Plant Components, Aerial ; Molecular Structure

Objective:To explore the risk factors associated with the clinical progression of COVID-19 infection in kidney transplant(KT)recipients during the spread of Omicron variant and evaluate the effectiveness of anti-RNA virus agents in blocking the clinical progression of COVID-19 in these recipients.Methods:Retrospective analysis was conducted for the clinical data on COVID-19 infection in 232 KT recipients followed up from December 4, 2022 to January 31, 2023 at Department of Renal Transplantation, Organ Transplantation Center, Beijing Tsinghua Changgung Hospital.Inclusion criteria were age ≥18 years and stable kidney function without renal replacement therapy.The follow-up time was 30 days after COVID-19 infection.Based upon whether or not there was an infection of COVID-19, KT recipients were divided into two groups of infection(181 cases)and non-infection(51 cases). In infection group, recipients were further assigned into two sub-groups of disease progression(n=23)and stable(158 cases)according to whether or not there was a progression to severe disease.Various factors such as gender, age, body mass index(BMI), time after transplantation, underlying diseases(history of hypertension, diabetes mellitus, coronary heart disease & chronic lung disease), smoking history and dosing of anti-RNA virus agents were collected.Pearson χ2 test or Fisher's exact probability method was utilized for examining enumeration data while Mann-Whitney U test for measurement data.Univariate Logistic regression analysis was conducted and variables with P<0.05 were included into multifactorial Logistic regression analysis to identify independent risk factors for clinical progression of COVID-19 infection in KT recipients. Results:Among 232 KT recipients, infection rate of COVID-19 was 78.0%(181/232). The clinical classification was mild(112 cases), moderate(46 cases), severe(21 cases)and critical(n=2 cases). The severe rate was 12.7%(23/181). After infection with COVID-19, the proportion of KT recipients aged ≥65 years progressing from mild/moderate to severe was higher than those aged<65 years[38.5%(5/13)vs 10.7%(18/168)]. The difference was statistically significant( P=0.014); The proportion of diabetic KT recipients progressing from mild/moderate to severe was higher than those without diabetes[19.1%(13/68)vs 8.8%(10/113)]. The difference was statistically significant( P=0.045). Univariate Logistic analysis showed similar results.Age≥65 years( OR=5.21, 95% CI: 1.54-17.64, P=0.008)or diabetes mellitus( OR=2.44, 95% CI: 1.003-5.911, P=0.049)were the risk factors for COVID-19 infection recipients progressing from mild/moderate to severe disease.Multivariate Logistic analysis revealed that age ≥65 years( OR=4.03, 95% CI: 1.14-14.34, P=0.031)was an independent risk factor for COVID-19 infection recipients progressing from mild/moderate to severe.Among 181 cases of COVID-19 mild/medium infected patients, 18 cases received nimativir/ritonavir and 10 cases had azvudine for anti-RNA virus treatment.However, none of them progressed to severe; 153 cases did not use anti-RNA virus drugs and 23 cases(15.0%)progressed to severe disease and the difference was statistically significant( P=0.028). Among 23 severe cases, 14 cases received nirmatrelvir/ritonavir and 2 cases had azivudine for anti-RNA virus treatment.The former did not progress to critical disease while 1 case in the latter progressed to critical illness and death; 1/7 recipients not using anti-RNA virus agents progressed to critical illness and died while another 6 cases did not progress to critical illness. Conclusions:KT recipients aged ≥65 years or diabetes mellitus have a greater risk of progression from mild/moderate to severe disease after COVID-19 infection.Among them, age ≥65 years is an independent risk factor for patients with COVID-19 infection to progress from mild/moderate to severe.Antiviral treatment with nirmatrelvir/ritonavir or azivudine in KT recipients during mild/moderate stage of COVID-19 infection can significantly reduce the rate of severe disease.Treatment with Nirmatrelvir/Ritonavir is still effective in the severe stage.

In recent years, modeling and simulation technology based on pharmacometrics has received increasing attention in the development of innovation drugs. In August of 2021, FDA issued a guidance named Pharmacokinetic-Based Criteria for Supporting Alternative Dosing Regimens of Programmed Cell Death Receptor-1 (PD-1) or Programmed Cell Death-Ligand 1 (PD-L1) Blocking Antibodies for Treatment of Patients with Cancer Guidance for Industry, claiming the necessity of using population PK-based simulation method for the optimization of dosing regimens, and the corresponding implementation standards. This article first summarized the existing therapeutic regimens of PD-1/PD-L1 blocking antibodies in clinic as well as the main content of the guidance, and then cited some actual examples where population PK-based simulation method did contribute to the approval of the alternative dosing regimens. Besides, some critical considerations for the dosing regimen optimization of PD-1/PD-L1 blocking antibodies were also analyzed. In our view, this guidance would have positive impacts on the development of PD-1/PD-L1 blocking antibodies in the future. We hope that this article may provide some references for the colleagues in China.

Objective:To explore the relationship between sleep quality and occupational stress in field gas recovery workers.Methods:In October 2018, cluster sampling method was adopted to conduct cross-sectional survey on 1726 field workers in a gas production oilfield. The individual characteristics, occupational stress factors, stress regulation factors, stress response and sleep quality, social support and coping strategies were evaluated by occupational stress measurement tools and job content questionnaire. Mann Whitney U test and Kruskal Wallis H test were used to compare sleep quality scores between the groups. Spearman rank correlation analysis was used to analyze the correlation between sleep quality and occupational stress, and logistic regression analysis was used to analyze multiple factors. Results:There were significant differences in sleep quality scores among different positions, gender, marital status, age, length of service, smoking and drinking ( P<0.05) . There were no significant differences in sleep quality scores between different education levels and work shift groups ( P>0.05) . Spearman rank correlation analysis showed that sleep quality score was negatively correlated with job satisfaction, reward, job stability, promotion opportunity, positive emotion, respect, self-esteem, control strategy, support strategy and self-efficacy score ( r s=-0.361, -0.311, -0.238, -0.261, -0.248, -0.212, -0.139, -0.188, -0.152, -0.226, P<0.01) , and was positively correlated with social support, giving, daily tension, negative emotion, work monotony and depression symptom ( r s=0.312, 0.279, 0.547, 0.493, 0.429, 0.599, P<0.01) . Compared with the high sleep quality score group, the middle and low sleep quality score groups had lower giving, work monotony, daily tension, depressive symptoms, negative emotions and social support ( P<0.01) , while the scores of respect, reward, job satisfaction, positive emotion, self-efficacy, job stability, promotion opportunity, control strategy and support strategy were higher ( P<0.01) . Multiple depressive symptoms, high daily tension, high negative emotion and high work monotony were the risk factors for sleep disorders ( OR=3.417, 2.659, 2.913, 1.543) . Conclusion:Depressive symptoms, daily tension and negative emotion have great influence on sleep quality of field gas recovery workers.

Objective:To investigate the level of social support and its correlation with occupational stress among gas production workers in the field.Methods:In October 2018, the cluster sampling method was used to perform a cross-sectional survey for 1726 gas production workers in the field, and related data of these workers were collected, including age, education level, marital status, level of social support, and related factors for occupational stress. A Spearman's rank correlation analysis was used to investigate the correlation between social support and occupational stress, and the levels of occupational stress-related factors were compared between the groups with different social support scores.Results:The gas production workers in the field had a median (25th percentile, 75th percentile) social support score of 24.00 (19.00, 28.00) , and there was a significant difference in social support score between the workers with different posts or work shifts ( P<0.01) . Social support score was positively correlated with effort, daily stress, negative emotion, and job routinization ( P<0.05) and was negatively correlated with job satisfaction, reward, working stability, and promotion opportunity ( P<0.05) . The group with a high social support score had significantly higher scores of effort, job routinization, sleep disorders, and daily stress than the other two groups ( P<0.01) , and the group with a low social support score had significantly higher scores of reward, self-efficacy, positive affection, and job satisfaction than the other two groups ( P<0.01) . Conclusion:High-level social support plays an important role in alleviating occupational stress and protecting mental health among gas production workers in the field.

Objective:To explore the relationship between sleep quality and occupational stress in field gas recovery workers.Methods:In October 2018, cluster sampling method was adopted to conduct cross-sectional survey on 1726 field workers in a gas production oilfield. The individual characteristics, occupational stress factors, stress regulation factors, stress response and sleep quality, social support and coping strategies were evaluated by occupational stress measurement tools and job content questionnaire. Mann Whitney U test and Kruskal Wallis H test were used to compare sleep quality scores between the groups. Spearman rank correlation analysis was used to analyze the correlation between sleep quality and occupational stress, and logistic regression analysis was used to analyze multiple factors. Results:There were significant differences in sleep quality scores among different positions, gender, marital status, age, length of service, smoking and drinking ( P<0.05) . There were no significant differences in sleep quality scores between different education levels and work shift groups ( P>0.05) . Spearman rank correlation analysis showed that sleep quality score was negatively correlated with job satisfaction, reward, job stability, promotion opportunity, positive emotion, respect, self-esteem, control strategy, support strategy and self-efficacy score ( r s=-0.361, -0.311, -0.238, -0.261, -0.248, -0.212, -0.139, -0.188, -0.152, -0.226, P<0.01) , and was positively correlated with social support, giving, daily tension, negative emotion, work monotony and depression symptom ( r s=0.312, 0.279, 0.547, 0.493, 0.429, 0.599, P<0.01) . Compared with the high sleep quality score group, the middle and low sleep quality score groups had lower giving, work monotony, daily tension, depressive symptoms, negative emotions and social support ( P<0.01) , while the scores of respect, reward, job satisfaction, positive emotion, self-efficacy, job stability, promotion opportunity, control strategy and support strategy were higher ( P<0.01) . Multiple depressive symptoms, high daily tension, high negative emotion and high work monotony were the risk factors for sleep disorders ( OR=3.417, 2.659, 2.913, 1.543) . Conclusion:Depressive symptoms, daily tension and negative emotion have great influence on sleep quality of field gas recovery workers.

Objective:To investigate the level of social support and its correlation with occupational stress among gas production workers in the field.Methods:In October 2018, the cluster sampling method was used to perform a cross-sectional survey for 1726 gas production workers in the field, and related data of these workers were collected, including age, education level, marital status, level of social support, and related factors for occupational stress. A Spearman's rank correlation analysis was used to investigate the correlation between social support and occupational stress, and the levels of occupational stress-related factors were compared between the groups with different social support scores.Results:The gas production workers in the field had a median (25th percentile, 75th percentile) social support score of 24.00 (19.00, 28.00) , and there was a significant difference in social support score between the workers with different posts or work shifts ( P<0.01) . Social support score was positively correlated with effort, daily stress, negative emotion, and job routinization ( P<0.05) and was negatively correlated with job satisfaction, reward, working stability, and promotion opportunity ( P<0.05) . The group with a high social support score had significantly higher scores of effort, job routinization, sleep disorders, and daily stress than the other two groups ( P<0.01) , and the group with a low social support score had significantly higher scores of reward, self-efficacy, positive affection, and job satisfaction than the other two groups ( P<0.01) . Conclusion:High-level social support plays an important role in alleviating occupational stress and protecting mental health among gas production workers in the field.

Carrier Proteins ; Humans ; Nutrition Surveys ; Nutritional Status ; Population Surveillance ; Xenopus Proteins

Objective To evaluate the clinical effect of popliteal artery perforator-based sural neurovascular flap for repairing soft tissue defects in middle and distal upper leg.Methods Between December,2011 to September,2015,18 cases with skin soft tissue defects on the middle and distal upper leg were treated with popliteal artery perforator-based sural neurovascular flap,in which 12 cases were males,and 6 cases were females.The age was from 24 to 55 years,with the average age of 35.9 years.The size of tissue defects ranged from 3.0 cm × 3.0 cm to 7.0 cm × 9.0 cm.Results All flaps survived completely in 18 cases,1 case of marginal infection heated after dressing,and the rest cases in Ⅰ healing.The outline and function of survived flap were satisfactory during 3-16 months follow-up,with two-point discrimination of 4.0-10.0 mm.Conclusion The anterograde sural neurovascular flap based on the popliteal artery perforator provides a practical option for covering tissue defects in middle and distal upper leg.This flap is characteristiced by reliable blood supply without sacrificing main vesses,good contour and texture,in addition,the operation is easy of handling.

OBJECTIVETo investigate the relationship between acute graft rejection early after renal transplantation and the variations of platelet parameters.

METHODSWe retrospectively analyzed the clinical data of 167 renal transplant recipients before and within 2 months after the surgery. Before and at 1-10 days, 15 days, 30 days, 45 days and 60 days after the transplantation, 5 platelet parameters, including platelet count (PLT), platelet hematocrit (PCT), mean platelet volume (MPV), platelet volume distribution width (PDW), and large platelet ratio (P-LCR), were detected in the 35 patients with acute graft rejection within two months (AR group) and in the other 132 recipients with good graft recovery (control group).

RESULTSThe AR group and control group showed no significant difference in PLT, PCT, MPV, or P-LCR before the surgery, but the PDW was significantly higher in the AR group (t=2.18, P=0.035). These parameters were similar within 5 postoperative days between the two groups (P>0.05), but in postoperative days 6-15, the AR group showed significantly increased MPV, PDW and P-LCR compared with the control group (P<0.05). In postoperative days 6-9, MPV, PDW and P-LCR became stable in AR group but tended to decrease in the control group, showing obviously different patterns of variation between the two groups (P<0.05).

CONCLUSIONSPreoperative PDW may have a positive correlation with acute graft rejection after renal transplantation. Monitoring the variations of MPV, PDW and P-LCR may help in the diagnosis of acute graft rejection early after renal transplantation.