Objective:To investigate the efficacy, safety and possible mechanisms of celecoxib as an adjunctive treatment for schizophrenia.Methods:90 schizophrenic inpatients at the second affiliated hospital of Xinxiang Medical College from April 2019 to October 2020 were recruited and randomly assigned to a placebo group or the celecoxib adjunctive treatment group using a random number table. In the placebo group, 46 patients (29 males, 17 females; aged 21-34, mean age 27.46±6.50 years) completed a 6-week follow-up. In the celecoxib group, 44 patients (32 males, 12 females; aged 21-39, mean age 30.52±8.69 years) completed a 6-week follow-up. The Positive and Negative Syndrome Scale (PANSS) was used to assess psychiatric symptoms in both groups. Changes in PANSS score at the end of the treatment were compared to evaluate the efficacy of celecoxib. Metabolic indicators such as weight, body mass index, waist circumference and plasm glucolipid, as well as cardiovascular indicators like blood pressure, electrocardiogram and routine blood tests, and adverse events were collected for the safety evaluation. Serum tumor necrosis factor-α (TNF-α), Interleukin-4 (IL-4) and interferon-γ (IFN-γ) were also tested. Pearson correlation analysis was used to explore the relationship between cytokine levels, PANSS score, PANSS reduction rate [(pre-treatment score-post-treatment score)/pre-treatment score×100%], and the safety measurements in the two groups, analyzing the role of inflammation in celecoxib adjunctive therapy.Results:The change of PANSS positive score at the end of the 6th week was significantly higher in the celecoxib adjuvant treatment group than in the placebo group (-8.00±6.12 vs -4.78±5.19, H=-0.55, P=0.009). The weight changes, body mass index, total cholesterol, and triglycerides over 6 weeks were significantly lower in the celecoxib group compared to the placebo group ( F=-7.37, -7.30, 2.56, -2.54; all P<0.05). No serious adverse events were found in celecoxib adjuvant therapy. In the placebo group, baseline TNF-α levels were positively correlated with baseline negative symptoms and PANSS reduction rate ( r=0.260 and 0.330, both P<0.05), and negatively correlated with the 6-week weight ( r=-0.311, P<0.05); baseline IL-4 levels were positively correlated with the 6-week PANSS total score and the 6-week PANSS negative score ( r=0.320 and 0.397, both P<0.05), and negatively correlated with PANSS reduction rate and 6-week blood glucose ( r=-0.316 and -0.331, both P<0.05); Six-week IFN-γ levels were negatively correlated with low-density lipoprotein levels ( r=-0.306, P<0.05). And no such correlation was found in celecoxib adjuvant group. Conclusion:Celecoxib adjunctive therapy can improve positive symptoms of schizophrenia without causing adverse reactions. Inflammatory state is related to schizophrenia symptoms, treatment efficacy and metabolic abnormalities.

Objective To explore the effect of quercetin on renal inflammation and cell apoptosis in diabetic rats and its possible mechanisms.Methods Twenty-four adult male SD rats were randomized equally into normal control group,high-glucose and high-fat feeding group,streptozotocin(STZ)-induced diabetic model group,and quercetin treatment(daily dose 100 mg/kg)group.Pathological changes of the renal tissues of the rats were observed with HE staining,serum inflammatory factor levels were determined with ELISA,and renal expression of NF-κB was observed by immunohistochemistry.Fast blood glucose(FBG),serum levels of triglyceride(TG),BUN,and Scr,and 24-h urine protein content of the rats were measured,and renal expressions of HMGB1,RAGE,NF-κB,Bax,Bcl-2,and caspase-3 were detected with Western blotting.Results The diabetic rats showed significantly increased levels of FBG,TG,BUN,and Scr,renal hypertrophy index,24-h urinary protein content,serum IL-1β,IL-6 and TNF-α levels and renal expressions HMGB1,RAGE,NF-κB,Bax,and caspase-3 with decreased renal expression of Bcl-2.All these changes were significantly alleviated by quercetin treatment of the rats.Conclusion Quercetin can ameliorate kidney injury in diabetic rats possibly by inhibiting the HMGB1/RAGE/NF-κB inflammatory signaling pathway to reduce renal inflammation and renal cell apoptosis.

Objective To explore the effect of quercetin on renal inflammation and cell apoptosis in diabetic rats and its possible mechanisms.Methods Twenty-four adult male SD rats were randomized equally into normal control group,high-glucose and high-fat feeding group,streptozotocin(STZ)-induced diabetic model group,and quercetin treatment(daily dose 100 mg/kg)group.Pathological changes of the renal tissues of the rats were observed with HE staining,serum inflammatory factor levels were determined with ELISA,and renal expression of NF-κB was observed by immunohistochemistry.Fast blood glucose(FBG),serum levels of triglyceride(TG),BUN,and Scr,and 24-h urine protein content of the rats were measured,and renal expressions of HMGB1,RAGE,NF-κB,Bax,Bcl-2,and caspase-3 were detected with Western blotting.Results The diabetic rats showed significantly increased levels of FBG,TG,BUN,and Scr,renal hypertrophy index,24-h urinary protein content,serum IL-1β,IL-6 and TNF-α levels and renal expressions HMGB1,RAGE,NF-κB,Bax,and caspase-3 with decreased renal expression of Bcl-2.All these changes were significantly alleviated by quercetin treatment of the rats.Conclusion Quercetin can ameliorate kidney injury in diabetic rats possibly by inhibiting the HMGB1/RAGE/NF-κB inflammatory signaling pathway to reduce renal inflammation and renal cell apoptosis.

Objective:To investigate the efficacy, safety and possible mechanisms of celecoxib as an adjunctive treatment for schizophrenia.Methods:90 schizophrenic inpatients at the second affiliated hospital of Xinxiang Medical College from April 2019 to October 2020 were recruited and randomly assigned to a placebo group or the celecoxib adjunctive treatment group using a random number table. In the placebo group, 46 patients (29 males, 17 females; aged 21-34, mean age 27.46±6.50 years) completed a 6-week follow-up. In the celecoxib group, 44 patients (32 males, 12 females; aged 21-39, mean age 30.52±8.69 years) completed a 6-week follow-up. The Positive and Negative Syndrome Scale (PANSS) was used to assess psychiatric symptoms in both groups. Changes in PANSS score at the end of the treatment were compared to evaluate the efficacy of celecoxib. Metabolic indicators such as weight, body mass index, waist circumference and plasm glucolipid, as well as cardiovascular indicators like blood pressure, electrocardiogram and routine blood tests, and adverse events were collected for the safety evaluation. Serum tumor necrosis factor-α (TNF-α), Interleukin-4 (IL-4) and interferon-γ (IFN-γ) were also tested. Pearson correlation analysis was used to explore the relationship between cytokine levels, PANSS score, PANSS reduction rate [(pre-treatment score-post-treatment score)/pre-treatment score×100%], and the safety measurements in the two groups, analyzing the role of inflammation in celecoxib adjunctive therapy.Results:The change of PANSS positive score at the end of the 6th week was significantly higher in the celecoxib adjuvant treatment group than in the placebo group (-8.00±6.12 vs -4.78±5.19, H=-0.55, P=0.009). The weight changes, body mass index, total cholesterol, and triglycerides over 6 weeks were significantly lower in the celecoxib group compared to the placebo group ( F=-7.37, -7.30, 2.56, -2.54; all P<0.05). No serious adverse events were found in celecoxib adjuvant therapy. In the placebo group, baseline TNF-α levels were positively correlated with baseline negative symptoms and PANSS reduction rate ( r=0.260 and 0.330, both P<0.05), and negatively correlated with the 6-week weight ( r=-0.311, P<0.05); baseline IL-4 levels were positively correlated with the 6-week PANSS total score and the 6-week PANSS negative score ( r=0.320 and 0.397, both P<0.05), and negatively correlated with PANSS reduction rate and 6-week blood glucose ( r=-0.316 and -0.331, both P<0.05); Six-week IFN-γ levels were negatively correlated with low-density lipoprotein levels ( r=-0.306, P<0.05). And no such correlation was found in celecoxib adjuvant group. Conclusion:Celecoxib adjunctive therapy can improve positive symptoms of schizophrenia without causing adverse reactions. Inflammatory state is related to schizophrenia symptoms, treatment efficacy and metabolic abnormalities.

Plasticity in the glutamatergic synapses on striatal medium spiny neurons (MSNs) is not only essential for behavioral adaptation but also extremely vulnerable to drugs of abuse. Modulation on these synapses by even a single exposure to an addictive drug may interfere with the plasticity required by behavioral learning and thus produce impairment. In the present work, we found that the negative reinforcement learning, escaping mild foot-shocks by correct nose-poking, was impaired by a single in vivo exposure to 20 mg/kg cocaine 24 h before the learning in mice. Either a single exposure to cocaine or reinforcement learning potentiates the glutamatergic synapses on MSNs expressing the striatal dopamine 1 (D1) receptor (D1-MSNs). However, 24 h after the cocaine exposure, the potentiation required for reinforcement learning was disrupted. Specific manipulation of the activity of striatal D1-MSNs in D1-cre mice demonstrated that activation of these MSNs impaired reinforcement learning in normal D1-cre mice, but inhibition of these neurons reversed the reinforcement learning impairment induced by cocaine. The results suggest that cocaine potentiates the activity of direct pathway neurons in the dorsomedial striatum and this potentiation might disrupt the potentiation produced during and required for reinforcement learning.

BACKGROUND: It is indicated in a large amount of basic researches that compound danshen di wan has a certain action on removing carotid atherosclerotic plaques (CAP), but there is lack of large sample data in randomized, controlled, multi-central clinical experiment.OBJECTIVE: To observe the removing action of compound danshen di wan on CAP, compared with aspirin.DESIGN: Multi-central, randomized controlled experiment was designed.SETTING: Research Center of Traditional Chinese Medicine and Ultrasonic Department of Xinjing Hospital, Fourth Military Medical University of Chinese PLA; Department of Traditional Chinese Medicine of Second Clinical Hospital, Xi' an Jiaotong University and Department of Cardiac Internal Medicine of Xi' an Hospital of Traditional Chinese Medicine.PARTICIPANTS: Totally 162 cases were selected from the clinic of Research Center of Traditional Chinese Medicine, Fourth Military Medical University of Chinese PLA; Department of Traditional Chinese Medicine, Second Clinical Hospital, Xi' an Jiaotong University and Department of Cardiac Internal Medicine of Xi' an Hospital of Traditional Chinese Medicine from 2002 to 2004, aged varied from 40 to 80 years, the thickness of carotid internal media ≥ 1.2 mm. They were randomized into two groups, named danshen di wan group of 89 cases(cases of soft plaque and hard plaque were 49 and 40 respectively) and aspirin group of 73 cases(cases of soft plaque and hard plaque were 42 and 31 respectively).METHODS: In danshen di wan group: compound danshen di wan was administrated orally(10 pills/time, 3 times/day), in aspirin group, enteric soluble aspirin table was administrated orally(75 mg/time, once a day),continuously for 6 months. The alternations of thickness of carotid internal media were determined with ultrasonic B of high resolving power before and after treatment.MAIN OUTCOME MEASURES: Changes in thickness of carotid internal media before and after treatment.RESULTS: By practical measuring analysis, 143 cases accomplished nation of thickness of carotid internal media in the patients with soft plaque:In danshen di wan group, the thickness was remarkably decreased after treatment[ (2. 12 ± 0. 34), (2.44± 0.40) mm, t = 4. 267, P ＜ 0.01 ] . In aspirin group, it was also reduced relatively after treatment[ (2.25 ± 0. 3),of carotid internal media in the patients with hard plaque: The changes were not significant no matter in danshen di wan group or aspirin group in the comparison before and after treatment[in danshen di wan group: (2.46 ±0.42),(2.34 ± 0. 40) mm; in aspirin group: (2.42 ± 0. 44), (2. 36 ± 0. 38) mm,P＞ 0.05].CONCLUSION: Compound danshen di wan acts on removing soft atherosclerotic plaque and its effect is similar to aspirin.

The application of resonance charging circuit to electro-hydraulic impulse apparatus for treating wastewater is introduced in this paper.The circuit permits the graduating increase of current without influence from time.The unique change of voltage on capacitor is favorable for the recovery of electric strength of electro-hydraulic impulse apparatus.The theory and design method of resonance charging circuit are provided.