Objective To establish a renal cell co-culture system to simulate the renal barrier system,and to test its responsiveness to different glucose concentrations,and to investigate the regulatory effect of miR-29b-3p on osteopontin(OPN)/transforming growth factor β(TGF-β)pathway and the changes of this pathway under high glucose condition.Methods The three-cell co-culture system consisting of human renal podocytes,human glomerular mesangial cells and human renal tubular epithelial cells was established to test the cell viability and glucose consumption value at glucose concentrations of 5,8,12 and 16 mmol/L.The content of TGF-β and OPN in cell supernatant was measured.The recombinant plasmid and siRNA of OPN were transfected,and the expressions of TGF-β and OPN were detected by Q-PCR and Western blot.Results The mRNA expressions of OPN,TGF-β and miR-29b were significantly increased at 12 mmol/L glucose conditions.Western blot results showed that the protein expression of OPN increased in high glucose conditions,while the protein expression of TGF-β did not change significantly.After adding miR-29b-3p activator,the mRNA levels of OPN and TGF-β in the cell supernatant were significantly increased.After adding miR-29b-3p inhibitor,the mRNA levels of OPN and TGF-β in the cell supernatant were significantly decreased.Western blot results showed that compared with 5 mmol/L glucose,the protein expressions of OPN and TGF-β were increased by miR-29b-3p activator,and the protein expressions of OPN and TGF-β were decreased by miR-29b-3p inhibitor.After transfection with OPN recombinant plasmid,the content of TGF-β in the cell supernatant was significantly increased,and the mRNA expressions of OPN and TGF-β in the cells were significantly increased.After transfection with OPN siRNA,the content of TGF-β in the cell supernatant was decreased,and the expression of OPN mRNA in the cells was significantly decreased,but the expression of TGF-β mRNA was not significantly increased.Conclusion The renal cell co-culture system can mimic the complex renal environment in vivo.When induced by high glucose,cell proliferation is inhibited,glucose consumption is increased,and the content of TGF-β in the cell supernatant is increased,and miR-29b-3p has a regulatory effect on OPN/TGF-β signaling pathway in the co-culture system.

Objective To investigate the effect of varying blood pressure stratification on renal function in the diabetic population.Methods A prospective cohort study was conducted,enrolling 9 489 diabetic patients from a total of 101 510 Kailuan Group employees who underwent health examinations between July 2006 and October 2007.The follow-up period was(8.6±4.0)years.Participants were categorized into four groups based on their baseline blood pressure levels:normal blood pressure(systolic blood pressure<120 mmHg and diastolic blood pressure<80 mmHg),elevated blood pressure(systolic blood pressure 120-130 mmHg and diastolic blood pressure<80 mmHg),stage 1 hypertension(systolic blood pressure 130-140 mmHg and/or diastolic blood pressure 80-90 mmHg),and stage 2 hypertension(systolic blood pressure≥140 mmHg and/or diastolic blood pressure≥90 mmHg).The incidence density of chronic kidney disease(CKD)was compared among these groups.A multivariate Cox proportional hazards regression model was employed to assess the effects of different blood pressure levels on renal function in diabetic patients,with the stability of the results confirmed using a multivariate time-dependent Cox proportional hazards model.Sensitivity analysis was conducted after excluding cases of cardiovascular disease(CVD)during follow-up,and cases using antihypertensive and antidiabetic medications at baseline.Results(1)At baseline,stage 1 hypertension patients demonstrated statistically significant higher differences with age and body mass index(BMI)compared to normal blood pressure group(P<0.05).(2)By the end of the follow-up,2 294 cases of CKD were identified,including 1 117 cases of estimated glomerular filtration rate(eGFR)decline and 1 575 cases of urinary protein.The incidences density of CKD,eGFR decline and urinary protein for stage 1 hypertension group were 39.4,16.3 and 25.5 per thousand person-years,respectively,all of which were statistically significant different from normal blood pressure group(log-rank test,P<0.01).(3)Multivariate Cox regression analysis revealed that,compared to the normal blood pressure group,stage 1 hypertension was associated with a 29%increased risk of CKD(HR=1.29,95%CI 1.09-1.52)and a 40%increased risk of eGFR decline(HR=1.40,95%CI 1.08-1.80)in diabetic individuals.Conclusion Stage 1 hypertension significantly increases the risk of CKD and eGFR decline in diabetic individuals,with a particularly notable effect on the risk of eGFR decline.

ObjectiveTo investigate the mechanism of Akkermansia muciniphila （A. muciniphila） regulating the visceral hypersensitivity in irritable bowel syndrome （IBS） rats induced by neonatal maternal separation （MS） and water avoidance stress （WAS）. MethodsNeonatal male Sprague-Dawley rats were randomly divided into sham WAS group （blank group）， MS+WAS group （IBS model group） and A. muciniphila group. IBS model was established by MS combined with WAS in both IBS model group and A. muciniphila group. Meanwhile， the rats in the A. muciniphila group were given 1 mL 1×10⁹ CFU/mL A. muciniphila by gavage daily for 10 days. Visceral pain responses were detected by behavioral observations and abdominal withdrawal reflex scores. ResultsCompared with IBS model group， A. muciniphila group exhibited significant increase of body weight and visceral pain threshold， significantly decreased numbers of fecal particles and proportions of unformed stools， significantly higher expression levels of cannabinoid receptor type 2 （CB₂R） mRNA in colon tissues. ConclusionA. muciniphila may alleviate the visceral hypersensitivity in IBS rats by regulating the expression of CB₂R mRNA in colonic tissues.

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.
Humans ; Aged ; Treatment Outcome ; Retrospective Studies ; Combined Modality Therapy ; Chemoradiotherapy/methods* ; Urinary Bladder Neoplasms/radiotherapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Neoplasm Staging

Chronic stress leads to many psychiatric disorders, including social and anxiety disorders that are associated with over-activation of neurons in the basolateral amygdala (BLA). However, not all individuals develop psychiatric diseases, many showing considerable resilience against stress exposure. Whether BLA neuronal activity is involved in regulating an individual's vulnerability to stress remains elusive. In this study, using a mouse model of chronic social defeat stress (CSDS), we divided the mice into susceptible and resilient subgroups based on their social interaction behavior. Using in vivo fiber photometry and in vitro patch-clamp recording, we showed that CSDS persistently (after 20 days of recovery from stress) increased BLA neuronal activity in all the mice regardless of their susceptible or resilient nature, although impaired social interaction behavior was only observed in susceptible mice. Increased anxiety-like behavior, on the other hand, was evident in both groups. Notably, the CSDS-induced increase of BLA neuronal activity correlated well with the heightened anxiety-like but not the social avoidance behavior in mice. These findings provide new insight to our understanding of the role of neuronal activity in the amygdala in mediating stress-related psychiatric disorders.
Amygdala ; Animals ; Anxiety/etiology* ; Anxiety Disorders ; Avoidance Learning ; Mice ; Mice, Inbred C57BL ; Social Behavior ; Stress, Psychological/complications*

Famous traditional formula Sanpian Decoction(SPD)comes from Dialectical Records of Chen Shiduo of the Qing Dynasty,and ranks among 100 classic prescriptions of Classic Famous Traditional Formula catalogue(the First Batch). SPD was prepared according to Management Standards for Traditional Chinese Medicine Decoction Room in Medical Institutions. According to the polarity of different components in SPD,two HPLC fingerprints were established, in which six herbs, namely Chuanxiong Rhizoma, Paeoniae Randix Alba, Sinapis Semen, Glycyrrhizae Radix et Rhizoma, Pruni Semen, Angelicae Dahuricae Radix,are all reflected in the fingerprints; The dry extract rate, transfer rate and similarities of fingerprints were used as indicators to study the relationship between the quality value transmitting of medicinal herbs-decoction pieces-whole decoction of Chuanxiong Rhizoma. Experiment result shows that,the transfer rate of ferulic acid from medicinal herbs to decoction pieces is between 72.00% and 108.36%; the transfer rate of ferulic acid from decoction pieces to SPD is between 31.76% and 64.09%; the dry extract rate of the whole decoction is between 14.69% and 20.16%;The similarity range of fingerprint 1 of 15 batches of SPD is between 0.971 and 0.998, and the similarity range of fingerprint 2 is between 0.980 and 0.996. The established fingerprint has rich information,and the established quality evaluation method is suitable for the quality control of medicinal herbs-decoction pieces-whole decoction of Chuanxiong Rhizoma, which can provide a certain reference for developing the quality control evaluation method for formulated granules, famous formulae and other terminal products derived from traditional Chinese medicine decoction.
Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/chemistry* ; Medicine, Chinese Traditional ; Quality Control ; Rhizome

To study and analyze prevalence condition of hypertension and complicated cardiovascular risk factors in north Fujian rural area .Methods : By cluster sampling , an epidemiological questionnaire and physical ex‐amination were performed among 1784 residents using standardized survey method , who were ≥35 years from six towns and eight villages in north Fujian rural area from Jun 2013 to Mar 2014. Hypertension was diagnosed accord‐ing to The 2010 Chinese Guideline for the Prevention and Treatment of Hypertension , multivariate Logistic regres‐sion was used to analyze independent risk factors for hypertension in these subjects .Results : Prevalence rate of hy‐ pertension was 17.43% (31／1784 ) in north Fujian rural area .After population standardization , it＇s 23. 21%(18.66% in men and 16. 13% in women) , there was no significant difference in prevalence rate of hypertension be‐tween men and women in any age layer , P＞0. 05 all.Multivariate Logistic regression analysis indicated that age , overweight (BMI≥24 kg／m2 ) , high triglyceride and fasting blood glucose were independent risk factors for hyper‐tension in north Fujian rural area (OR＝1.107－2.096 , P＜0. 05 or ＜0. 01).Conclusion : Prevalence rate of hyper‐tension is high in north Fujian rural area , age , overweight , smoking , high triglyceride and fasting blood glucose are the main risk factors .

Objective: To compare the middle and long term clinical outcomes of one-stop hybrid coronary revascularization, coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) in treating the patients with multivessel coronary artery disease; to explore the optimal indication of one-stop hybrid technology. Methods: Our research included in 3 groups: Hybrid group, n=141 patients received one-stop hybrid coronary revascularization in our hospital from 2006-06 to 2010-16. Meanwhile, 5797 patients received CABG and 4254 received PCI, the major pre-operative risk factors were studied by Logistic regression analysis to calculate propensity score, adjacent matching was used to respectively select 141 subjects from CABG and PCI patients to make 1:1 match with Hybrid group as CABG group and PCI group. EuroSCORE and SYNTAX score were used to make risk stratification in all 3 groups. By EuroSCORE system: low risk ≤ 2, medium risk (3-5) and high risk ≥ 6; by SYNTAX score system: low risk ≤ 24, medium risk (25-29) and high risk ≥ 30. The incidence of major adverse cardiac/cerebral vascular events (MACCE) was compared among 3 groups at different risk stratifications. Results: The mean follow-up time was 4.5 years up to 2015-01. The overall incidence of MACCE was lower in Hybrid group (9.9％) than PCI group (27.7％), P<0.001; while it was similar between Hybrid group and CABG group (19.1％), P=0.150. By EuroSCORE stratification, the incidence of MACCE in low risk and medium risk patients were similar among 3 groups; while in high risk patients, the incidence was lower in Hybrid group than both CABG group (P=0.017) and PCI group (P<0.001). By SYNTAX score stratification, the incidence of MACCE in low risk and medium risk patients were similar among 3 groups; while in high risk patients, the incidence was lower in Hybrid group than PCI group (P<0.001), it was similar between Hybrid group and CABG group (P=0.355). Conclusion: One-stop hybrid technology had the better middle and long term outcomes for treating multivessel coronary artery disease patients with high risk stratification, which provided an alternative strategy in clinical practice.

Objective To investigate the correlation between TRIM29 expression and non-small cell lung cancer (NSCLC) and its different histological types and clinicopathological features. Methods Using computer retrieves data databases such as PubMed, EMbase, China Knowledge Network and Wanfang Data, and collects relevant case-control studies at home and abroad. The time for searching the literature is as of August 1, 2018. Meta-analysis of the relationship between TRIM29 positive expression and clinicopathological features and tissue typing of non-small cell lung cancer was conducted by Review Manager 5.3 software. Results Five studies were included, including 1061 in the NSCLC group and 918 in the control group. Meta-analysis showed statistically significant differences between the expression of TRIM29 between NSCLC group and the control group [OR=18.32, 95％CI (4.62, 72.67), P<0.0001], squamous cell carcinoma and adenocarcinoma group [OR=37.05, 95％CI (2.45, 559.73), P=0.009], NSCLC lymph node metastasis group and NSCLC lymph node without metastasis group [OR=5.62, 95％CI (2.83, 11.17), P<0.00001], NSCLC (Ⅰ+Ⅱ) and (Ⅲ+Ⅳ) [OR=0.18, 95％CI (0.10, 0.32), P<0.00001] and NSCLC well differentiated group and the NSCLC middle and low differentiated group [OR=0.12, 95％CI (0.07, 0.21), P<0.00001], respectively. Conclusions The expression of TRIM29 is significantly correlated with NSCLC and its histological classification, lymph node metastasis, clinical stage and histological grade. This paper has certain help and reference value for the histological and clinical pathological features of NSCLC patients.

BackgroundSleep disturbance is one of the major non-motor symptoms which cause the disability of Parkinson's disease (PD) patients. Cystatin C (CysC) is a more sensitive biomarker than serum creatinine or estimated glomerular filtration rate. Previous studies have reported altered CysC levels in neurodegenerative disorders and sleep disorders. This study aimed to explore the correlations of serum CysC levels and objective sleep disturbances in early PD.

MethodsWe recruited 106 early PD patients and 146 age- and sex-matched controls. All participants underwent clinical investigation and video-polysomnography. Sleep parameters and serum levels of CysC were measured. Then, we investigated the relationships between CysC and clinical variables and objective sleep disturbances in early PD patients.

ResultsThe mean serum level of CysC was significantly higher in patients with early PD (1.03 ± 0.19 mg/L) compared to controls (0.96 ± 0.15 mg/L, P = 0.009). There were significantly positive correlations between serum CysC levels and age (r = 0.334, P < 0.001), gender (r = 0.264, P = 0.013), and creatinine levels (r = 0.302, P = 0.018) in early PD patients. Increased serum CysC levels in early PD patients were significantly associated with higher apnea and hypopnea index (AHI) (r = 0.231, P = 0.017), especially hypopnea index (r = 0.333, P < 0.001). In early PD patients, elevated serum CysC levels were positively correlated with oxygen desaturation index (r = 0.223, P = 0.021), percentage of time spent at oxygen saturation (SaO) <90% (r = 0.644, P < 0.001), arousal with respiratory event during sleep (r = 0.247, P = 0.013). On the contrary, the elevated serum CysC levels were negatively correlated with mean and minimal SaO(r = -0.323, -0.315, both P = 0.001) in PD patients.

ConclusionsThe level of serum CysC was higher in early PD patients. PD patients with elevated serum CysC levels had more respiratory events and more severe oxygen desaturation. Therefore, the serum CysC levels may predict the severities of sleep-disordered breathing problems in early PD patients.

Aged ; Cystatin C ; blood ; Female ; Glomerular Filtration Rate ; physiology ; Humans ; Male ; Middle Aged ; Parkinson Disease ; blood ; physiopathology ; Polysomnography ; Sleep Wake Disorders ; blood ; physiopathology