Huajuxiaoji Formula Alleviates Phenyl Sulfate-Induced Diabetic Kidney Disease by Inhibiting NLRP3 Inflammasome Activation and Pyroptosis.

Background: One of the most common microvascular complications of diabetes is diabetic kidney disease (DKD). The Huajuxiaoji formula (HJXJ) has shown clinical efficacy for DKD; however, its regulatory mechanisms against DKD remain elusive. We investigated NLRP3 inflammasome and the mechanisms of HJXJ by which HJXJ alleviates DKD. Methods: Phenyl sulfate (PS) was used to establish DKD models. HJXJ was administered to mice through intragastric or made into a pharmaceutical serum for the cell cultures. Biological indicator levels in mouse blood and urine were analyzed, and kidney tissues were used for HE, Masson, and PAS staining. ELISA and western blotting were used to detect inflammatory cytokines and protein levels, respectively. Reactive oxygen species (ROS) production and pyroptosis were evaluated using flow cytometry. Lentiviral vector-mediated overexpression of NLRP3 was performed to determine whether NLRP3 participates in the antipyroptotic effect of HJXJ. Results: HJXJ significantly reduced the severity of the injury and, in a dose-dependent manner, decreased the levels of biological markers including creatinine, blood urea nitrogen, urine protein, and endotoxin, as well as inflammatory cytokines such as interleukin (IL)-1ß, IL-18, tumor necrosis factor-α, and IL-6 in DKD mice. Treatment with HJXJ reversed the downregulation of podocin, nephrin, ZO-1, and occludin and upregulated ROS, NLRP3, Caspase-1 P20, and GSDMD-N induced by PS. Moreover, the upregulation of NLRP3 expression increased the number of cells positive for pyroptosis. HJXJ suppressed pyroptosis and inflammasome activation by inhibiting NLRP3 expression. Conclusions: Generally, HJXJ has the potential to reduce DKD injury and exerts anti-DKD effects by inhibiting the NLRP3-mediated NLRP3 inflammasome activation and pyroptosis in vitro and in vivo.

[Acupuncture for delayed sleep-wake phase disorder: a randomized controlled trial].

OBJECTIVE: To observe the clinical effect of acupuncture for delayed sleep-wake phase disorder (DSWPD). METHODS: A total of 84 patients with DSWPD were randomized into an observation group (42 cases, 2 cases dropped off) and a control group (42 cases, 3 cases dropped off). On the basis of sleep hygiene education, acupuncture was applied at Shenmai (BL 62), Zhaohai (KI 6), Hegu (LI 4), Taichong (LR 3), Zusanli (ST 36) and Sanyinjiao (SP 6) in the observation group, while placebo acupuncture was applied at the same acupoints in the control group. The treatment lasted for 8 weeks, once every other day, 3 times a week in the 1st to 4th weeks; once every 3 days, 2 times a week in the 5th to 8th weeks. Before and after treatment, the actigraphy (ACT) indexes of objective sleep (total time of stay in bed, total sleep time, sleep efficiency, the number of awakenings and the wake time after falling asleep) and plasma cortisol (CORT) level were observed; before and after treatment and in follow-up of 1, 3 months after treatment, the scores of morningness-eveningness questionnaire (MEQ), insomnia severity index (ISI), fatigue severity scale (FSS) and Epworth sleepiness scale (ESS) were observed in the two groups. RESULTS: Compared before treatment, the total sleep time was prolonged, the sleep efficiency was improved, the number of awakenings was reduced, and the wake time after falling asleep was shortened after treatment in the observation group (P<0.01, P<0.05), and those in the observation group after treatment were superior to the control group (P<0.01, P<0.05). Compared before treatment, the MEQ scores after treatment in both groups and in the follow-up of 1, 3 months after treatment in the observation group were increased (P<0.01), and the MEQ score of each time point after treatment in the observation group was higher than the control group (P<0.01). The scores of ISI, FSS and ESS after treatment, and the scores of ISI、ESS in follow-up of 1, 3 months after treatment in the observation group were decreased compared with those before treatment (P<0.01, P<0.05), and in the observation group, the scores of ISI, FSS and ESS of each time point after treatment were lower than those in the control group (P<0.01, P<0.05). After treatment, the plasma CORT level in the observation group was decreased compared with that before treatment and that in the control group (P<0.01, P<0.05). CONCLUSION: Acupuncture can improve the sleep and wake phase of patients with DSWPD, improve sleep quality and daytime function, and its mechanism may be related to the down-regulation of plasma CORT level.

Psychological Impact During the First Outbreak of COVID-19 on Frontline Health Care Workers in Shanghai.

Background: The COVID-19 pandemic is a significant health threat. Health care worker (HCWs) are at a significant risk of infection which may cause high levels of psychological distress. The aim of this study was to investigate the psychological impact of the COVID-19 on HCWs and factors which were associated with these stresses during the first outbreak in Shanghai. Methods: Between February 9 and 21, 2020, a total of 3,114 frontline HCWs from 26 hospitals in Shanghai completed an online survey. The questionnaire included questions on their sociodemographic characteristics, 15 stress-related questions, and General Health Questionnaire-12 (GHQ-12). Exploratory factor analysis was applied to the 15 stress-related questions which produced four distinct factors for evaluation. Multiple linear regression models were performed to explore the association of personal characteristics with each score of the four factors. Binary logistic analysis was used to explain the association of personal characteristics and these four factors with the GHQ-12. Results: There were 2,691 valid surveys received. The prevalence of emotional distress (defined as GHQ-12 ≥ 12) was noted in 47.7% (95%CI:45.7-49.6%) HCWs. Females (OR = 1.43, 95%CI:1.09-1.86) were more likely to have a psychological distress than males. However, HCWs who work in secondary hospitals (OR = 0.71, 95% CI:0.58-0.87) or had a no contact history (OR = 0.45, 95%CI: 0.35-0.58) were less likely to suffer psychological distress. HCWs who were nurses, married, and had a known contact history were highly likely to have anxiety. HCWs working at tertiary hospitals felt an elevated anxiety regarding the infection, a lack of knowledge, and less protected compared to those who worked at secondary hospitals. Conclusions: Our study shows that the frontline HCWs had a significant psychosocial distress during the COVID-19 outbreak in Shanghai. HCWs felt a lack of knowledge and had feelings of being not protected. It is necessary for hospitals and governments to provide additional trainings and psychological counseling to support the first-line HCWs.

Strong Association of Serum GSK-3ß/BDNF Ratio with Mild Cognitive Impairment in Elderly Type 2 Diabetic Patients.

BACKGROUND: Glycogen Synthase Kinase (GSK)-3ß and Brain-derived Neurotrophic Factor (BDNF) play vital roles in both Mild Cognitive Impairment (MCI) and Type 2 Diabetes Mellitus (T2DM). The underlying mechanisms may involve inflammation and oxidative stress. OBJECTIVES: To investigate the association of the GSK-3ß/BDNF ratio with MCI in elderly patients with T2DM and whether GSK-3ß/BDNF ratio can serve as a new diagnostic biomarker for MCI in comorbid with T2DM (MD). METHODS: A total of 326 old Chinese T2DM patients were included and stratified according to cognition and GSK-3ß/BDNF ratio quartiles. MCI was diagnosed according to the National Institute on Aging Alzheimer's Association workgroups criteria. In addition to routine hematuria and biochemical examinations, Montreal Cognitive Assessment (MoCA) scale was also used to evaluate the cognitive function, and ELISA method was used to measure GSK-3ß activity and the serum levels of BDNF, interleukin 1ß (IL-1ß), high mobility group box-1 (HMGB1) protein, Malonaldehyde (MDA) and 8-isoprostaglandinF2α (8-iso-PGF2α). RESULTS: We found that GSK-3ß activity was negatively correlated with BDNF (r=-0.270, P=0.008), and patients with higher GSK-3ß/BDNF ratio had lower MoCA scores (P=0.001). When compared with T2DM patients without MCI (nMD), MD patients had higher GSK-3ß activity and GSK-3ß/BDNF ratio, but lower BDNF levels. As for inflammation and oxidative stress, IL-1ß was inversely correlated with GSK-3ß activity, while 8-isoPGF2α was positively correlated with GSK-3ß activity and GSK-3ß/BDNF ratio. The odds ratio for MCI increased gradually when GSK-3ß/BDNF ratio quartile rose from the lowest to the highest (6.90, 95% CI 3.22-14.78). MoCA score was conversely related to GSK-3ß/BDNF ratio, age and fast blood glucose (FBG), with GSK-3ß/BDNF ratio having the most significant influence on cognition (ß=-0.199, P<0.001). CONCLUSION: Our data provide evidence for a strong link between GSK-3ß/BDNF ratio and MCI. GSK- 3ß/BDNF ratio may serve as a better diagnostic biomarker for MD than either GSK-3ß or BDNF alone and increased GSK-3ß/BDNF ratio indicates a worse cognitive function.

Clinical study on Yishen Qufeng Shengshi Recipe () for glomerular proteinuria patients: A randomized controlled trial.

OBJECTIVE: To explore the therapeutic effect of Yishen Qufeng Shengshi Recipe (, YQSR) in patients with glomerular proteinuria METHODS: A total of 145 patients with glomerular proteinuria were selected and randomly assigned to the treatment group (108 cases) and the control group (37 cases) according to a random number table in a ratio of 3:1. All patients received conventional and symptomatic treatment. In addition, patients in the treatment and control groups were given YQSR (200 mL, twice per day, orally) and losartan (50 mg/d orally), respectively for 6 months. The 24-h urine protein quantity, blood urea nitrogen, and serum creatinine in the two groups were measured at multiple time points before and after treatment. RESULTS: At the end of the study, 5 cases were lost to follow-up in the treatment group and 1 in the control group. Finally, the statistical data included 103 cases in the treatment group and 36 cases in the control group. The total effectiveness after 2, 4, and 6 months was 81.6% (84/103), 87.4% (90/103), and 92.2% (95/103), respectively, in the treatment group and 47.2% (17/36), 55.6% (20/36), and 61.1% (22/36), respectively, in the control group, with significant difference between the two groups (P<0.01 at all observation points). In the treatment group, the curative effect after 6 months was better than that after 2 months (P<0.05). The 24-h urine protein quantity was significantly lower in the treatment group at 3, 4, 5, and 6 months than that in the control group (P<0.05 or P<0.01, respectively) CONCLUSION: YQSR could significantly reduce the amount of glomerular proteinuria in the early stage.

[Treatment of Proteinuria in Chronic Glomerular Disease Patients with Pi-Shen Deficiency Complicated Damp-Heat Syndrome by Yishen Qingre Huashi Recipe: a Clinical Study].

OBJECTIVE: To observe the therapeutic effect of Yishen Qingre Huashi Recipe (YQHR) in treating proteinuria of chronic glomerular disease patients with Pi-Shen deficiency complicated damp-heat syndrome (PSDCDHS). METHODS: Totally 121 stage 1 -2 primary chronic glomerular disease patients with PSDCDHS were randomly assigned to the treated group (85 cases) and the control group (36 cases) according to 2:1. All patients received conventional and symptomatic treatment. Patients in the treated group took YQHR additionally, while those in the control group took Losartan Potassium Tablet (50 mg each time, once per day) additionally. The therapeutic course for all was 6 months. Changes of 24 h urine protein, blood urea nitrogen (BUN), serum creatinine(SCr), and estimated glomerular filtration rate (eGFR) were observed at different time points. And the difference in therapeutic effects were compared between the two groups. RESULTS: Compared with the control group after 6 months of treatment, 24 h urine protein obviously decreased in the treated group (P <0. 05). There was no statistical difference in SCr, BUN, or eGFR between the two groups after 6 months of treatment (P >0. 05). The total effective rate after 2, 4, and 6 months of treatment in the treated group was 77. 6% (66/85 cases), 82. 4% (70/85 cases), and 89. 4% (76/85 cases), respectively. They were 47. 2% (17/36 cases), 55. 6% (20/36 cases), and 61. 1% (22/36 cases) in the control group, respectively. Compared with before treatment in the treated group, the total effective effect after 6 months of treatment was higher than that after 2 months of treatment (χ2=4. 28, P <0. 01). Compared with the control group at the same time points, the total effective rate in the treated group after 2, 4, and 6 months of treatment was higher (χ2=10. 87, 9. 53, 13.16, P <0. 01). CONCLUSION: YQHR could significantly lower proteinuria in chronic glomerular disease patients with PSDCDHS, improve the clinical effect, thereby providing clinical evidence for treating chronic glomerular disease proteinuria from resolving dampness and clearing heat.

[Multi-center randomized control study on the effects of syndrome differentiated traditional Chinese medicine therapy on CKD 1-2 with chronic nephritis proteinuria].

OBJECTIVE: To determine the effects of Syndrome Differentiated Chinese Medicine (TCM) Therapy on (CKD) 1-2 stage chronic kidney disease with proteinuria. METHODS: A prospective randomized control study was undertaken in 11 centers. A total of 396 chronic nephritis patients were divided into a treatment group (n=297) and a control group (n=99). Their TCM syndrome was classified as "Qi and Yin Deficiency of spleen and kidney" or "Qi and Yang Deficiency of spleen and kidney", with accompanying syndromes showing as "water and dampness", "damp-heat", and "blood stasis". Patients in the treatment group took a dose of Chinese medicine daily in response to their syndromes, while the controls took 50 mg/d losartan. The course of treatment was 24 weeks. Changes of 24-hour urinary protein excretion and glomerular filtration rate (eGFR) before and after treatments (4, 8, 12, 16, 20, 24 weeks), as well as clinical efficacy (after 4, 16, 24 weeks treatments) were measured. RESULTS: 361 patients were included in the final program participants comply analysis (PPS). Patients in the treatment group showed gradual decreased 24-hour urinary protein excretion, whereas the controls remained unchanged. Significant differences in 24-hour urinary protein excretion appeared between the experimental and control group at week 20 and 24 (P<0.05). eGFR decreased in all of the patients after treatments (P=0.0014). At three follow-up points, patients in the treatment group had higher eGFR than the controls, but without statistical significance (P>0.05). Significant differences in clinical remission rate, marked effect rate and total effective rate were observed between the treatment and control groups at week 24 (P<0.001). CONCLUSION: Syndrome differentiated TCM therapy can reduce the level of proteinuria in CKD 1-2 nephritis patients, promoting clinical effectiveness and protecting renal functions.

[Syndrome differentiation-based treatment with traditional Chinese medicine for proteinuria in patients with chronic kidney disease: a randomized multicenter trial].

OBJECTIVE: To evaluate the clinical efficacy of syndrome differentiation-based treatment with traditional Chinese medicine (TCM) versus losartan therapy in addition to basic treatment for management of proteinuria in patients with chronic kidney disease. METHODS: This multicenter, randomized, and case-controlled clinical trial was conducted among 81 consecutive patients meeting the inclusion criteria. The patients were randomized consecutively to receive TCM treatments according to the syndrome patterns in TCM (spleen and kidney Qi and Yin deficiency, and spleen and kidney Qi and Yang deficiency, n=60) or oral losartan therapy (50 mg/day, n=21) in addition to the basic treatments. All the patients were followed up for 24 weeks to observe the clinical effects. RESULTS: The patients in TCM group showed a significantly higher overall response rate (93.33%) than those in losartan group (76.20%, P<0.05). The TCM score in the two groups were all decreased at week 24 as compared with baseline (P<0.01 or P<0.05). The TCM scores in both groups decreased significantly after the treatments as compared with the baseline scores (P<0.05). After a 8-week-long treatment, Scr, eGFR and Cys-C, U-Pro/24 h, and MA/Cr all decreased significantly in TCM group (P<0.05) but showed no significant changes in losartan group (P>0.05). CONCLUSION: Syndrome differentiation-based TCM treatment in addition to basic treatments can produce satisfactory therapeutic effects on proteinuria in patients with chronic kidney disease by improving the clinical symptoms, reducing TCM symptom scores and proteinuria, and protecting the renal functions.