Phosphodiesterases(PDE)are involved in the regulation of cellular physiological processes and neurological functions,including neuronal plasticity,synapto-genesis,synaptic transmission,memory formation and cognitive functions by catalyzing the hydrolysis of intracellular cyclic adenosine monophosphate(cAMP)and cyclic guanosine monophosphate(cGMP).Many basic and clinical studies have shown that PDE4 inhibitors block or ameliorate the occurrence and development of central nervous system(CNS)diseases by inhibiting cAMP hydrolysis,increasing cAMP content and enhancing its downstream effects.PDE4 inhibitors have long-term potentiation effect,which can enhance phosphorylation of cAMP response element binding protein(CREB)and upregulate expression of memory related Arc genes in hippocampal neurons,thereby improving cognitive impairment and Alzheimer's disease-like symptoms.They can also delay the occurrence and development of Parkinson's disease by reducing the cytotoxicity induced by α-syn and increasing the effect of miR-124-3p on cell functions.Alteration of PDE4 activity is the molecular basis for psychosis and some cognitive disorders,therefore it is considered as a therapeutic target for schizophrenia.PDE4 inhibitors play a role in depression by inhibiting the advanced glycation end product receptor(RAGE),TLR4 and NLRP3 pathways in the hippocampus,reducing the activation of microglia and the production of IL-1β,down-regulating HMGB1/RAGE signaling pathway and inhibiting inflammatory factors.PDE4 inhibitor plays a role in the treatment of autism spectrum disorder by reducing the damage of cerebellar glial cells,increasing nociceptive threshold,and improving mutual learning and memory deficits.PDE4 inhibitors might be used in the treatment of fragile X syndrome by regulating the level of cAMP and affecting the expression of fragile X mental retardation protein(FMRP).PDE4 inhibitors can also promote the differentiation of oligodendrocyte progenitor cells and enhance myelination,which has potential in the treatment of multiple sclerosis.PDE4 is also related to bipolar disorder,which may be one of the therapeutic targets.At present,several PDE4 inhibitors are in clinical trials for the treatment of CNS diseases.This article reviews and discusses the progress on basic research and clinical trials of PDE4 inhibitors in CNS diseases,providing a reference for the prevention and treatment of CNS diseases and the development of new drugs.

Objective:To predict and analyze the number of acute pancreatitis (AP) inpatients based on time series model, and to explore the predictive efficiency of the model.Methods:Clinical data of AP inpatients in the Affiliated Hospital of Southwest Medical University from January 2014 to December 2019 were collected. R software was used to collect the time series of AP inpatients, and the trend and seasonal characteristics of AP inpatients from 2014 to 2018 were analyzed. Furthermore, the autoregressive moving average (ARIMA) model was established through stationarity test, model ordering and model testing steps, and the best selected model was used to predict the monthly number of inpatients in 2019 to verify its prediction efficiency.Results:A total of 3 939 AP patients were included in the study. The most common etiology for AP was cholestrogenic (48.2%), followed by hyperacylglyceremia (36.3%). The peak age of hospitalization was from 40 to 60 years old. Time series analysis showed that the number of AP inpatients increased year by year. The highest peak of the disease was from February to March, followed by September to November; and there was seasonal variation and the incidence was relatively small in summer. The established original training set sequence did not pass the stationarity test ( P=0.061), so the ARIMA model was established after it was transformed into a stationarity sequence by first-order difference. According to the criterion of minimum AIC value, ARIMA(2, 1, 1)(1, 1, 1) 12 was selected as the best model. The model was used to predict the number of AP inpatients in 2019, showing that it could better fit the trend of onset time and had good short-term prediction effect. The mean root error and absolute error were 6.8790 and 4.7783, respectively. Conclusions:The number of AP inpatients increases year by year with seasonal changes. ARIMA model is effective in predicting the number of AP inpatients and can be used for short-term prediction.

ObjectiveTo investigate the condom use of men who have sex with men （MSM） in Shanghai， the information motivation behavioral skills model （IMB） theory was used to introduce psychosocial factors and study the relevant factors of consistent condom use （CCU） in this population. MethodsA cross-sectional study of 547 MSM in four districts of Shanghai was conducted by snowball sampling. The structural equation model based on psychosocial optimization was constructed and validated using the data collected by structured questionnaires. ResultsAmong the 547 respondents， the proportion of CCU in the past six months was 45.5%. Comparing the fitness of the initial model with that of the adjusted model， we found that the fitness of the adjusted model was good. ConclusionThe proportion of CCU among MSM in Shanghai is relatively low； In addition， information and motivation do not directly affect the CCU of this population； Only behavioral skills have a direct effect on CCU. Finally， social psychological measures should be emphasized for this population， and comprehensive and multi-level strategies should be formulated to control the spread of HIV in this population.

Objective:To evaluate the feasibility of Full-stack Smart Pelvic Floor Ultrasound (FSPFU) software in the acquisition and measurement of the minimal levator hiatus (LH).Methods:Transperineal pelvic floor ultrasonography was performed in 119 women of 6-month postpartum from Nov.2020 to Jan.2021 of Shenzhen Second People′s Hospital. Mid-sagittal plane of pelvic floor was set as the initial plane, and the three-dimensional volume data was acquired. The dataset was stored in the machine. The offline volume data was manually adjusted to obtain the minimal LH images and measured by four physicians (two junior physicians as the D1 group and two senior physicians as the D2 group). For comparison, the results were also obtained using the fully automated method—the FSPFU software by a junior physician (the D3 group). The obtained parameters of minimal LH included area, circumference, anterioposterior diameter, transverse diameter, left and right levator-urethral gap distance. Analysis time was recorded for each group. The contours of minimal LH were outlined by three groups and the overlapping rate was calculated. The quality of the resulted images was evaluated and scored by another two senior physicians(A and B) independently.Results:The D3 group had a significant shorter analysis time compared with the other two groups, and the D1 group took a longer time than the D2 group, regardless of the cystocele severity (D1: 82.97 s, D2: 62.51 s, D3: 2.71 s, all P<0.05). The intergroup agreements and correlations of the minimum LH area were good (all ICC>0.85, rs>0.70, P<0.001) and the outlined contours were largely overlapped (>92%). There was no significant difference in image quality among the three groups(all P>0.05). Conclusions:FSPFU software can automatically obtain and measure the minimum LH in an efficient and accurate way, which can improve the effectiveness of the present pelvic floor examination. FSPFU software can be an useful tool in the diagnosis of pelvic floor dysfunctional diseases.

Objective:To evaluate the methodological quality and reporting quality of clinical practice guidelines or consensuses in the field of Chinese pancreatic diseases from 2016 to 2021, and provide reference for formulating clinical practice guidelines and consensuses in this field.Methods:VIP, Wanfang , CNKI and CBM databases were searched for articles published from January 2016 to March 2021. The main index terms were " pancreas" , " guideline" , " consensus" , and the supplementary index terms were " pancreatitis" , " pancreatic cancer" , " pancreatic head cancer" . Two researchers independently selected the literature. The appraisal of guidelines for research and evaluation (AGREE-China) was utilized to assess the methodological quality of the guidelines or consensuses, and the reporting items for practice guidelines in healthcare (RIGHT) tool was used to assess the reporting quality.Results:A total of 14 literature were included, including 7 literature on pancreatic cancer, 3 literature on acute pancreatitis, 1 literature on chronic pancreatitis and 3 literature on others. The results of the assessment by the AGREE-China tool showed that there were no document with a total score greater than or equal to 60.0 points, two with 40.0 to 59.9 points, eleven with 20.0 to 39.9 points, and one with less than 20.0 points. Among the results of RIGHT list, basic information was reported the highest(72.62%) and funding and declaration was the lowest(0).Conclusions:The methodological and reporting quality of the guidelines or consensuses on pancreatic disease in China from 2016 to 2021 are generally not high. In the process of developing domestic guidelines or consensuses on pancreatic diseases, the guideline developer should refer to AGREE-China and RIGHT to improve the quality of clinical practice guidelines or consensuses.

Objective:To analyze the registration status of acute pancreatitis-related clinical studies registered on the Chinese Clinical Trial Registry (ChiCTR) and USA ClinicalTrials.gov database.Methods:The ChiCTR and ClinicalTrials.gov database were searched to collect, sort and analyze the clinical studies related to acute pancreatitis registered from the establishment of the database to December 31, 2020. The clinical trials were manually grouped, and the features of clinical researches were compared based on different registered data (2007-2014 vs 2015-2020) and different financial sources (self-support, enterprise support or public support). Results:A total of 157 registered clinical studies related to acute pancreatitis have been included (ChiCTR n=99; ClinicalTrial.gov n=58). The top three areas with the greatest number of registered clinical studies were Sichuan (28.0%), Shanghai (14.6%) and Jiangsu (12.1%), totally accounting for 54.7%. There were 91 interventional studies, 41 observational studies and 25 other type studies. Masking was performed in 34 studies (21.6%). Randomized parallel controlling was performed in 84 studies (53.5%). 30 trials (19.1%) were at Ⅳ phase, and 7 trials (4.4%) were at Ⅱ or Ⅲ phase. 2007-2014 group tended to use randomized parallel controlled design (68.3% vs 45.4%, P=0.005) and randomization grouping (76.7% vs 47.4%, P=0.001). 2015-2020 group tended to use relatively large sample (72.6% vs 47.4%, P=0.002)and data management committee (53.6% vs 25.0%, P=0.001). The differences between the two groups were statistically significant. Of 92 trials from ChiCTR database, 48 were self-supported, 5 was supported by enterprise, and 38 was supported by the public. The percentage of self-support and public support was 86.9%. Conclusions:The number of acute pancreatitis-related clinical studies registered on ChiCTR was generally on the increase. Most registered studies were funded by public finances or by the researchers' institutions self. There was a lack of phaseⅡ or phase Ⅲ.

Inflammatory bowel disease is a recurrent chronic intestinal inflammatory disease with unknown etiology and no effective treatment. Phosphodiesterase (PDE) regulates a variety of physiological and pathophysiological processes by mediating the hydrolysis of intracellular second messengers cyclic adenosine monophosphate and cyclic guanosine monophosphate. In recent years, a series of researches suggest that PDE inhibitors such as several PDE4 inhibitors, PDE5 inhibitors (sildenafil, tadalafil and vardenafil), PDE3 inhibitors (cilostazol), PDE9 inhibitor (PF-04447943) and PDE3/PDE4 double inhibitor (pumafentrine) have ameliorating effect on experimental colitis in animals. In clinical trials, PDE4 inhibitor apremilast showed more therapeutic advantage than tetomilast. This article reviews the recent research progress of PDE inhibitors in treatment of inflammatory bowel disease.
Animals ; Colitis ; Inflammatory Bowel Diseases/drug therapy* ; Phosphodiesterase 4 Inhibitors

Aging/metabolism* ; Animals ; Gene Expression Regulation ; Macaca fascicularis ; Retina/metabolism* ; Single-Cell Analysis