Current Status and Challenges of Biological Sample Management in Clinical Trials / 中国医学伦理学

With the rapid development of clinical trials, the relevant medical research and molecular detection based on biological samples are closely related to the progress of clinical trials, making the role of biological samples in clinical trials increasingly obvious. The standardized supervision mode of biological samples is an important prerequisite for carrying out high-quality clinical trials. Although the laws and regulations related to clinical trials are becoming more and more perfect, there are still a large number of adverse events related to biological samples, which seriously affects the progress and results of clinical trials, and is one of the important challenges currently facing. Therefore, it is urgent to enhance the supervision of biological samples and improve the management methods of biological samples in clinical trials at this stage. Through in-depth discussion of the current status of biological sample management in clinical trials at home and abroad, this paper analyzed the issues existed during the supervision of biological samples, and supplemented the biological sample management methods by further combing the existing relevant laws and regulations and the Guidelines for the Ethical Management of Biological Samples in Clinical Trials, with a view to providing suggestions and ideas for optimizing the management mode of biological samples in clinical trials.

Surveillance and analysis of avian influenza viruses in the external environment of poultry in Anqing City， Anhui Province / 上海预防医学

ObjectiveTo determine the prevalence of avian influenza viruses in the external environment of poultry in Anqing City， Anhui Province， and provide scientific evidence for prevention and control of animal-derived influenza in humans. MethodsA total of 28 farmers’ markets/farms in 10 counties （cities， districts） of Anqing City， Anhui Province， were selected as surveillance sites by simple random sampling strategy. Poultry faeces and other related samples were collected for 6 consecutive weeks. Real-time fluorescence quantitative PCR was used to examine the nucleic acids of influenza A virus. Subtypes H5， H7， and H9 of avian influenza virus were further tested in the positive samples. ResultsA total of 426 specimens were collected， among which 113 tested positive with a positive rate of 26.53%. Among the positive specimens， 104 were determined to be subtype H9， accounting for 92.04%. It did not significantly differ in the positive rate between the main and non-main urban areas （χ2<0.01， P>0.05） or among the specimens collected in different weeks （χ2=7.57， P>0.05）. However， it significantly differed in the positive rate among the specimens collected in the third week and other weeks （χ2=6.89， P<0.05）. Furthermore， among the different sampling sites， farms had the highest positive rate of 46.67%. Among the specimens from different sources， the surface-coated specimens from poultry cages had the highest positive rate of 34.78%. ConclusionAvian influenza viruses are prevalent in the external environment of poultry in Anqing City. It warrants strengthening the surveillance and risk assessment to reduce the virus transmission in the external environment and risk of human infection with animal-derived influenza.

Protein Kinase CK2 Modulates the Calcium Sensitivity of Type 3 Small-conductance Calcium-activated Potassium Channels in Colonic Platelet-derived Growth Factor Receptor Alpha-positive Cells From Streptozotocin-induced Diabetic Mice

Background/Aims@#The gastrointestinal symptom of diabetes mellitus, chronic constipation, seriously affects patients’ life. Whereas, the mechanism of chronic constipation is still ambiguous, resulting in a lack of effective therapies for this symptom. As a part of the smooth muscle cells, interstitial cells of Cajal, and platelet-derived growth factor receptor alpha-positive (PDGFRα+ ) cells syncytium (SIP syncytium), PDGFRα+ cells play an important role in regulating colonic motility. According to our previous study, in PDGFRα+cells in colons of diabetic mice, the function of the P2Y1 purinergic receptor/type 3 small-conductance calcium-activated potassium (SK3) channel signaling pathway is strengthened, which may lead to colonic dysmotility. The purpose of this study is to investigate the changes in SK3 channel properties of PDGFRα+ cells in diabetic mice. @*Methods@#Whole-cell patch clamp, Western blotting, superoxide dismutase activity measurement, and malondialdehyde measurement were main methods in the present study. @*Results@#The present study revealed that when dialysed with low calcium ion (Ca 2+ ) solution, the SK3 current density was significantly decreased in PDGFRα+ cells from diabetic mice. However, the SK3 current density in PDGFRα+ cells was enhanced from diabetic mice when dialysed with high Ca 2+ solution. Moreover, hydrogen peroxide-treatment mimicked this phenomenon in SK3 transgenic HEK293 cells. The subunit of SK3 channels, protein kinase CK2, was up-regulated in colonic muscle layers and hydrogen peroxidetreated HEK293 cells. Additionally, protein phosphatase 2A, the subunit of SK3 channels, was not changed in streptozotocin-treated mouse colons or hydrogen peroxide-treated HEK293 cells. @*Conclusion@#The diabetic oxidative stress-induced upregulation of CK2 contributed to modulating SK3 channel sensitivity to Ca 2+ in colonic PDGFRα+ cells, which may result in colonic dysmotility in diabetic mice.

Research progress on cancer-related fatigue induced by radiotherapy / 中华放射肿瘤学杂志

Cancer-related fatigue (CRF) is a symptom associated with cancer and cancer treatment. The incidence of CRF during radiotherapy is extremely high and severely affects the quality of life and treatment compliance of patients. Although more and more studies on CRF have been carried out, the pathogenesis of CRF caused by radiotherapy is still not well understood, and systemic interventions remain to be improved. In this article, the pathogenesis, influencing factors, and interventions of CRF caused by radiotherapy were reviewed, aiming to provide reference for optimizing treatment options in clinical practice.

Course of disease and related epidemiological parameters of COVID-19: a prospective study based on contact tracing cohort / 中华预防医学杂志

Objective: To analyze the course of disease and epidemiological parameters of COVID-19 and provide evidence for making prevention and control strategies. Methods: To display the distribution of course of disease of the infectors who had close contacts with COVID-19 cases from January 1 to March 15, 2020 in Guangdong Provincial, the models of Lognormal, Weibull and gamma distribution were applied. A descriptive analysis was conducted on the basic characteristics and epidemiological parameters of course of disease. Results: In total, 515 of 11 580 close contacts were infected, with an attack rate about 4.4%, including 449 confirmed cases and 66 asymptomatic cases. Lognormal distribution was fitting best for latent period, incubation period, pre-symptomatic infection period of confirmed cases and infection period of asymptomatic cases; Gamma distribution was fitting best for infectious period and clinical symptom period of confirmed cases; Weibull distribution was fitting best for latent period of asymptomatic cases. The latent period, incubation period, pre-symptomatic infection period, infectious period and clinical symptoms period of confirmed cases were 4.50 (95%CI:3.86-5.13) days, 5.12 (95%CI:4.63-5.62) days, 0.87 (95%CI:0.67-1.07) days, 11.89 (95%CI:9.81-13.98) days and 22.00 (95%CI:21.24-22.77) days, respectively. The latent period and infectious period of asymptomatic cases were 8.88 (95%CI:6.89-10.86) days and 6.18 (95%CI:1.89-10.47) days, respectively. Conclusion: The estimated course of COVID-19 and related epidemiological parameters are similar to the existing data.

Clinical factors associated with composition of lung microbiota and important taxa predicting clinical prognosis in patients with severe community-acquired pneumonia / 医学前沿

Few studies have described the key features and prognostic roles of lung microbiota in patients with severe community-acquired pneumonia (SCAP). We prospectively enrolled consecutive SCAP patients admitted to ICU. Bronchoscopy was performed at bedside within 48 h of ICU admission, and 16S rRNA gene sequencing was applied to the collected bronchoalveolar lavage fluid. The primary outcome was clinical improvements defined as a decrease of 2 categories and above on a 7-category ordinal scale within 14 days following bronchoscopy. Sixty-seven patients were included. Multivariable permutational multivariate analysis of variance found that positive bacteria lab test results had the strongest independent association with lung microbiota (R2 = 0.033; P = 0.018), followed by acute kidney injury (AKI; R2 = 0.032; P = 0.011) and plasma MIP-1β level (R2 = 0.027; P = 0.044). Random forest identified that the families Prevotellaceae, Moraxellaceae, and Staphylococcaceae were the biomarkers related to the positive bacteria lab test results. Multivariable Cox regression showed that the increase in α-diversity and the abundance of the families Prevotellaceae and Actinomycetaceae were associated with clinical improvements. The positive bacteria lab test results, AKI, and plasma MIP-1β level were associated with patients' lung microbiota composition on ICU admission. The families Prevotellaceae and Actinomycetaceae on admission predicted clinical improvements.

Pirfenidone alleviates urethral stricture following urethral injury in rats by suppressing TGF-β1 signaling and inflammatory response / 南方医科大学学报

OBJECTIVE@#To investigate the effect of pirfenidone for reducing urethral stricture following urethral injury in rats and explore the possible mechanism.@*METHODS@#Thirty male SD rats were randomly assigned into negative control group, positive control group and pirfenidone group (n=10). In pirfenidone and positive control groups, the rats were subjected to incision of the posterior urethral cavernous body followed by daily intraperitoneal injection of pirfenidone (100 mg/kg) and an equivalent volume of solvent, respectively. The rats in the negative control group were given intraperitoneal injections of solvent without urethral injury. At two weeks after modeling, retrograde urethrography was performed for observing urethral stricture, and the injured urethral tissues were harvested for HE staining, Masson staining, immunohistochemical staining and Western blotting for detecting the protein expressions of α-SMA and TGF-β1. The mRNA expressions of the inflammatory factors TNF-α, IL-6, and IL-1β were detected using qRT-PCR.@*RESULTS@#The body weight of the rats in pirfenidone group was significantly decreased compared with that in the other two groups (P < 0.05). Retrograde urethrography showed significant narrowing of the urethra in the positive control group but not in the pirfenidone group. HE staining of the injured urethral tissues showed obvious proliferation of urethral epithelial cells with narrow urethral cavity and increased inflammatory cells in positive control group. The pathological findings of the urethra were similar between pirfenidone group and the negative control group. Masson staining revealed obviously reduced collagen fibers and regular arrangement of the fibers in pirfenidone group as compared to the positive control group. Compared with those in the negative control group, the expressions of α-SMA and TGF-β1 were significantly increased in the positive control group, and pirfenidone treatment significantly inhibited their expressions (P < 0.05 or 0.01). Pirfenidone also significantly inhibited the mRNA expressions of TNF-α, IL-6, and IL-1β in the injured urethral tissue (P < 0.05 or 0.01).@*CONCLUSION@#Pirfenidone can prevent urethral fibrosis and stricture after urethral injury possibly by inhibiting the TGF-β1 pathway and inflammatory response.

Analysis on SARS‑CoV‑2 contamination in the environment exposure to the SARS‑CoV‑2 cases in Huangpu District of Shanghai in 2022 / 中国热带医学

@#Abstract: Objective　To analyze the detection of SARS‑CoV‑2 in household environment and public place environment of Huangpu District, and describe the feature of SARS‑CoV‑2 contamination in the environment exposure to the infected cases, so as to support the control strategies such as disinfection and health communication. Methods　The results of RT-PCR test for the environmental samples exposure to the cases infected by SARS‑CoV‑2 during February 1 to March 31 2022 in Huangpu District of Shanghai were collected as the research data. Pearson χ2 was used to test the significance of the differences between positive rates of SARS‑CoV‑2 contamination. Results　From February 1 to March 31, household environment samples had a higher positive rate (6.47%, 234/3 618) of SARS‑CoV‑2 contamination while the public place samples had a lower one (1.22%, 47/3 582) in Huangpu District of Shanghai (χ2=141.908, P<0.01). Among the household buildings, the lane houses of old style representing poorer living condition had the highest positive rates (8.31%, 96/1 155) of SARS‑CoV‑2 contamination while the apartments representing better living condition had the lowest (3.59%, 22/612) (F=5.25，P<0.05). Among the samples from household environment, samples regarding sewerage had the highest positive rates (13.30%,58/436) of SARS‑CoV‑2 contamination, while samples regarding the tool of cooking and sweeping had the lowest (3.10%,17/548) (F=9.84，P<0.01). Among the samples from public place environment, samples regarding entertainment tools had the highest positive rates (13.33%, 2/15) of SARS‑CoV‑2 contamination, while samples regarding the tool of cooking and sweeping had the lowest (0.62%, 4/646) (F=4.22，P<0.01). Conclusion　In the environment exposure to the SARS‑CoV‑2 infected cases, the disinfection, ventilation and cleaning should be intensified strictly. SARS‑CoV‑2's surviving in sewage environment should be evaluation dynamically. More health communication should be pushed to people of poorer living condition.

Suicide attempts in Chinese Han patients with schizophrenia: cognitive, demographic, and clinical variables

Objective: The purpose of this study was to investigate the lifetime suicide attempt rate, clinical characteristics and cognitive function of Chinese patients with chronic schizophrenia who had attempted suicide. Methods: We collected data from 908 schizophrenia inpatients about suicide attempts through interviews with the patients and their families, as well as through medical records. All patients were assessed with the Positive and Negative Syndrome Scale, the Rating Scale for Extrapyramidal Side Effects, the Abnormal Involuntary Movement Scale, and the Repeated Battery for the Assessment of Neuropsychological Status. Results: Of this sample, 97 (10.68%) had attempted suicide. Patients who had attempted suicide were younger, had longer illness duration, and more severe general psychopathology and depressive symptoms than those who had not. Logistic regression analysis confirmed that suicide attempts were correlated with age, smoking, and depression. No cognitive performance differences were observed between patients who had and had not attempted suicide. Conclusions: In China, patients with chronic schizophrenia may have a higher prevalence of lifetime suicide attempts than the general population. Some demographic and clinical variables were related to suicide attempts in patients with chronic schizophrenia.

Biomechanical Analysis of Stroke Hemiplegic Patients During Sit-to-Stand Transfer / 医用生物力学

Due to damage to the hemi-advanced central nervous system of stroke hemiplegic patients, their ability of sit-to-stand transfer is impaired, and they are prone to fall during the sit-to-stand transfer. This article describes the characteristics of sit-to-stand transfer for hemiplegic patients at different foot placement from a biomechanical perspective, discusses the correlation between different features, analyzes the reasons for their fall, and describes the application of sit-to-stand transfer training in postoperative rehabilitation of hemiplegic patients， so as to provide references for postoperative rehabilitation of hemiplegic patients.

Single center retrospective analysis of emergency endoscopic therapy timing in esophagogastric variceal bleeding / 中国医师杂志

Objective:To investigate the optimal emergency endoscopy timing in patients with esophagogastric variceal bleeding (EGVB).Methods:The clinical data of patients with EGVB emergency endoscopy in Renmin Hospital of Wuhan University from December 2018 to November 2020 were collected and analyzed. According to the time interval from admission to the start of emergency endoscopy, they were divided into emergency endoscopy group (<6 h, n=115) and early endoscopy group (6-24 h, n=57). The baseline data, clinical efficacy and postoperative situation of the two groups were compared, and the risk factors of 6-week mortality of EGVB emergency endoscopy were analyzed by univariate and multivariate analysis. Results:In terms of baseline characteristics, there were no significant differences in age, gender, causes, shock index, model for end-stage liver disease (MELD) score, charlson complication index (CCI) score, portal hypertension related complications between the two groups ( P<0.05). However, the albumin (ALB) in emergency endoscopy group was significantly lower than that in early endoscopy group ( P<0.001). There were significant differences in Child Pugh grading and Child Pugh score between the two groups ( P=0.002, P=0.001). In terms of endoscopic efficacy, the detection rate of bleeding site in emergency endoscopy group was significantly higher than that in early endoscopy group (90.4% and 73.7%, P<0.05). There was no significant difference in operation duration, immediate hemostasis success rate, 5-day rebleeding rate, rescue treatment demand and 6-week mortality between the two groups ( P>0.05). There was no significant difference in bleeding related death between the two groups ( P>0.05). In addition, there was no significant difference in blood product consumption, intensive care unit (ICU) stay and total hospital stay between the two groups ( P>0.05). Multivariate analysis showed that Child Pugh grade C ( P=0.018), MELD score ( P=0.005) and CCI score ( P=0.001) were independent risk factors for 6-week death outcome of EGVB patients, while emergency endoscopic intervention time was not related to 6-week death outcome ( P=0.5). Conclusions:The efficacy of early endoscopic intervention is no worse than that of emergency endoscopic intervention, except for the identification of bleeding site. Child-Pugh grade C, MELD score, and CCI score are the independent risk factors for 6-week mortality, while the timing of emergency endoscopy is not associate with 6-week mortality in EGVB patients.

Risk factors and diagnostic methods of intensive care unit-acquired weakness / 中华危重病急救医学

Objective:To explore the risk factors of intensive care unit-acquired weakness (ICU-AW) and the characteristics of Medical Research Council (MRC) score and electromyogram.Methods:A case control study was conducted. Patients with mechanical ventilation ≥ 7 days and MRC score admitted to department of respiratory and critical care medicine of China-Japan Friendship Hospital from September 2018 to January 2020 were enrolled, and they were divided into ICU-AW group (MRC score < 48) and non-ICU-AW group (MRC score ≥ 48) according to MRC score. The general situation, past medical history, related risk factors, MRC score, respiratory support mode, laboratory examination results, electromyogram examination results, ICU-AW related treatment, outcome and length of ICU stay were collected, and the differences between the two groups were compared. The risk factors of ICU-AW were analyzed by binary multivariate Logistic regression, and the characteristics of MRC score and electromyogram were analyzed.Results:A total of 60 patients were enrolled in the analysis, including 17 patients in ICU-AW group and 43 patients in non-ICU-AW group. Univariate analysis showed that there were significant differences in acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, sequential organ failure assessment (SOFA) score, brain natriuretic peptide (BNP), blood urea nitrogen (BUN) on the first day of ICU admission and the ratio of invasive mechanical ventilation between ICU-AW group and non-ICU-AW group [APACHEⅡ score: 21 (18, 25) vs. 18 (15, 22), SOFA score: 7 (5, 12) vs. 5 (3, 8), BNP (ng/L): 364.3 (210.1, 551.2) vs. 160.1 (66.8, 357.8), BUN (mmol/L): 9.9 (6.2, 17.0) vs. 6.0 (4.8, 9.8), invasive mechanical ventilation ratio: 88.2% vs. 46.5%, all P < 0.05]. Binary multivariate Logistic regression analysis showed no independent risk factor for ICU-AW. The average MRC score of 17 ICU-AW patients was 33±11. The limb weakness was symmetrical, and the proximal limb weakness was the main manifestation. Electromyography examination showed that the results of nerve conduction examination in ICU-AW patients mainly revealed that the amplitude of compound muscle action potential (CMAP) and sensory nerve action potentials (SNAP) were decreased, and the conduction velocity was slowed down; needle electromyography showed increased area of motor unit potential (MUP), prolonged time limit and a large number of spontaneous potentials. Prognosis evaluation showed that compared with non-ICU-AW group, patients in ICU-AW group underwent more tracheotomy (70.6% vs. 11.6%), longer length of ICU stay (days: 57±52 vs. 16±8), and more rehabilitation treatment (58.8% vs. 14.0%), and the differences were statistically significant (all P < 0.01). Conclusions:The occurrence of ICU-AW may be related to high APACHEⅡ score and SOFA score, high levels of BNP and BUN on the first day of ICU admission and the proportion of invasive mechanical ventilation, but the above factors are not independent risk factors for ICU-AW. The MRC score of ICU-AW patients was characterized by symmetrical limb weakness, mainly proximal limb weakness; in electromyography examination, the nerve conduction examination results mainly showed that CMAP and SNAP amplitude were decreased, and conduction velocity was slowed down; needle electromyography examination showed increased MUP area, prolonged duration and a large number of spontaneous potentials.

Occupational Radiation Exposure and Changes in Thyroid Hormones in a Cohort of Chinese Medical Radiation Workers / 生物医学与环境科学（英文）

Objective@#This study aimed to evaluate the association between occupational radiation exposure and changes in thyroid hormone levels among medical radiation workers.@*Methods@#This retrospective cohort study included 2,946 radiation workers from 20 Guangzhou hospitals. Data on general characteristics, participant radiation dosimetry, and thyroid function test results [thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroid hormone (T4)] were extracted from dosimetry and medical records. The generalized estimating equation was used to evaluate the trend of changes in thyroid hormone levels over time and was adjusted for age, gender, and occupation.@*Results@#The average annual effective dose was very low and showed a general downward trend. During the follow-up period, changes in T3 and T4 levels among radiation workers were -0.015 [95% confidence interval ( @*Conclusion@#Thyroid hormone secretion might be affected even in low-dose radiation exposure environments.

Analyzing the abnormal results of personal dose monitoring of medical radiation workers / 中国职业医学

OBJECTIVE: To analyze the abnormal results and their causes of personal dose monitoring on medical radiation workers.METHODS: The medical radiation workers monitored from 2016 to 2019 in the personal dose monitoring room of Guangdong Province Hospital for Occupational Disease Prevention and Treatment were selected as the study subjects using convenient sampling method. The abnormal results and their causes of the medical radiation workers with personal dose equivalent ≥1.25 mSv(investigation level) in a single period were analyzed. RESULTS: The rate of abnormal results of personal dose monitoring was 0.26%(263/102 284). The false result rate was 0.19%(194/102 284), and that of the true result rate was 0.07%(69/102 284). A total of 73.38%(193/263) of medical radiation workers had abnormal results with an personal dose equivalent less than 5.00 mSv. Among different occupational groups, the abnormal results and false results in personal dose monitoring in interventional radiology group were the highest(all P<0.01). The abnormal result rate and false result rate were higher in the Pearl River Delta area than that in the non-Pearl River Delta area(0.27% vs 0.17%, 0.20% vs 0.12%, all P<0.05). The rate of false result of personal dose monitoring in the tertiary hospitals was lower than that in the non-tertiary hospitals(0.18% vs 0.30%, P<0.05). The main reason for the true results of personal dose monitoring was the increase of workload(43.48%), and the main reason for the false results was that the dosimeter was left in the workplace(57.73%). CONCLUSION: The rate of abnormal results of personal dose monitoring in the medical radiation workers is high. Radiological protection should be strengthened with emphasis on medical radiation workers in interventional radiology, Pearl River Delta area hospitals and non-tertiary hospitals.

Correlation between vascular wall characteristics and ischemic stroke and its mechanism in patients with atherosclerotic middle cerebral artery stenosis: a high-resolution MRI study / 国际脑血管病杂志

Objective:To investigate the correlation between vascular wall characteristics and ischemic stroke and its mechanism in patients with atherosclerotic middle cerebral artery (MCA) stenosis.Methods:Patients with atherosclerotic MCA stenosis received high-resolution vessel wall imaging (HR-VWI) in Shenzhen Bao'an District People's Hospital from November 2017 to November 2018 were enrolled retrospectively. The imaging characteristics, such as the lumen and vessel diameter and vessel wall area at the narrowest level of MCA plaque, plaque load, remodeling index, and plaque enhancement rate were measured. A multivariate logistic regression model was used to identify the independent risk factors for stroke in patients with atherosclerotic MCA stenosis. Results:A total of 53 patients with atherosclerotic MCA stenosis were enrolled, aged (53.5±9.7) years, 28 were male (52.8 %). There were 28 in the stroke group and 25 in the non-stroke group. Thirteen patients were artery-artery embolization, 15 were non-artery-artery embolization; 39 were mild stenosis, and 14 were moderate to severe stenosis. Compared with the non-stroke group, the moderate to severe stenosis was more common in the stroke group ( P=0.010), the plaque load was greater ( P=0.006), and the remodeling index was lower ( P=0.010). Multivariate logistic regression analysis showed that the remodeling index was an independent risk factor for stroke in patients with atherosclerotic MCA stenosis (odds ratio 0.002, 95% confidence interval 0.000-0.952; P=0.048). Compared with the non-artery-artery embolization group, the mean thickness of MCA was larger in the artery-artery embolization group ( P=0.037). Compared with the mild stenosis group, the plaque load was greater ( P=0.001), the plaque enhancement rate was higher ( P=0.004), and remodeling index was lower ( P<0.001) in the moderate to severe MCA stenosis group. Conclusions:In the atherosclerotic MCA stroke group, patients with moderate to severe stenosis are more common, with greater plaque load and lower remodeling index. Remodeling index is an independent risk factor for ischemic stroke. Patients with moderate to severe MCA stenosis have a higher plaque enhancement rate and a lower remodeling index, suggesting that the vessel wall inflammatory response is more significant and had decompensation. HR-VWI is expected to be used to assess the pathogenesis of ischemic stroke events.

Role of platelet-derived growth factor receptor α positive cells in purinergic inhibitory nerve-smooth muscle transmission / 生理学报

Under physiological conditions, the motility of smooth muscle in digestive tract is mainly regulated by enteric nervous system (ENS). However, how neural signal is transmitted to smooth muscle is not fully understood. Autonomic nerve endings in the smooth muscle layer form large number of varicosities which contain neurotransmitters. It was considered that nerve pulses arriving at the varicosities may cause the release of neurotransmitters, which may diffuse to the smooth muscle cells to induce contractile or relaxant responses. Over the past decade, a new understanding of the neurotransmission between ENS and smooth muscle has emerged, which emphasizes the role of a functional syncytium consisting of the interstitial cells of Cajal (ICC), the platelet-derived growth factor receptor α positive (PDGFRα) cells and the smooth muscle cells. Within the syncytium, purine neurotransmitters bind to P2Y1 receptors on PDGFRα cells, activating small-conductance calcium activated potassium channel (SK3) to hyperpolarize PDGFRα cells, and thus hyperpolarize smooth muscle cells through gap junction, resulting in relaxation of smooth muscle. In this paper, we review the research progress in the field of inhibitory purinergic neurotransmission in the gastrointestinal tract.

Role of penehyclidine in acute organophosphorus pesticide poisoning / 世界急诊医学杂志（英文）

BACKGROUND@#Penehyclidine is a newly developed anticholinergic agent. We aimed to investigate the role of penehyclidine in acute organophosphorus pesticide poisoning (OP) patients.@*METHODS@#We searched the Pubmed, Cochrane library, EMBASE, Chinese National Knowledge Infrastructure (CNKI), Chinese Biomedical literature (CBM) and Wanfang databases. Randomized controlled trials (RCTs) recruiting acute OP patients were identified for meta-analysis. Main outcomesincluded cure rate, mortality rate, time to atropinization, time to 60% normal acetylcholinesterase (AchE) level, rate of intermediate syndrome (IMS) and rate of adverse drug reactions (ADR).@*RESULTS@#Sixteen RCTs involving 1,334 patients were identified. Compared with the atropine-or penehyclidine-alone groups, atropine combined with penehyclidine significantly increased the cure rate (penehyclidine+atropine vs. atropine, 0.97 vs. 0.86, RR 1.13, 95% CI [1.07–1.19]; penehyclidine+atropine vs. penehyclidine, 0.93 vs. 0.80, RR 1.08, 95% CI [1.01–1.15]) and reduced the mortality rate (penehyclidine+atropine vs. atropine, 0.015 vs. 0.11, RR 0.17, 95% CI [0.06–0.49]; penehyclidine+atropine vs. penehyclidine, 0.13 vs. 0.08, RR 0.23, 95% CI [0.04–1.28]). Atropine combined with penehyclidine in OP patients also helped reduce the time to atropinization and AchE recovery, the rate of IMS and the rate of ADR. Compared with a single dose of atropine, a single dose of penehyclidine also significantly elevated the cure rate, reduced times to atropinization, AchE recovery, and rate of IMS.@*CONCLUSION@#Atropine combined with penehyclidine benefits OP patients by enhancing the cure rate, mortality rate, time to atropinization, AchE recovery, IMS rate, total ADR and duration of hospitalization. Penehyclidine combined with atropine is likely a better initial therapy for OP patients than atropine alone.

Comprehensive Evaluation of Differences of Pinelliae Rhizoma Germplasm Resources Based on AHP and Grey Correlation Method / 中国实验方剂学杂志

Objective::To establish the evaluation method of Pinelliae Rhizoma (PR) resources by the analytic hierarchy process (AHP) and grey correlation degree (GCD) method, so as to explore the differences in quality components, production efficiency and appearance traits of different germplasm resources cultivated in the same environment. Method::The quality component index, efficiency index, and appearance traits index of 15 germplasm resources were measured, including moisture, total ash, extractives, total acid content, harvest index, yield, drying rate, commodity rate, decay rate and deformability of tubers. Based on AHP and grey correlation method, each indicator data was processed in a comprehensive way, its comprehensive correlation value was calculated, and different PR germplasm resources were comprehensively evaluated. Result::Based on three factors-quality composition, production efficiency and appearance traits, the comprehensive correlation value of A6 was the highest, reaching 0.749 4, which was followed by A14, A15, A7, and their comprehensive correlation values were 0.736 6, 0.726 2, 0.718 2, respectively. Therefore, the source of A6 could be used as an excellent provenance introduced to the cultivation of PR, and the provenance of A14, A15, and A7 could be used as a useful supplement. Conclusion::The method of AHP and GCD-based multi-index comprehensive evaluation is simple and comprehensive to evaluate the diversity of different PR germplasm resources, and could provide a reference for the development and utilization of resources and the screening of high-quality provenances.

Colonic Dysmotility in Murine Partial Colonic Obstruction Due to Functional Changes in Interstitial Cells

BACKGROUND/AIMS: Interstitial cells play important roles in gastrointestinal (GI) neuro-smooth muscle transmission. The underlying mechanisms of colonic dysmotility have not been well illustrated. We established a partial colon obstruction (PCO) mouse model to investigate the changes of interstitial cells and the correlation with colonic motility. METHODS: Western blot technique was employed to observe the protein expressions of Kit, platelet-derived growth factor receptor-α (Pdgfra), Ca²⁺-activated Cl⁻ (Ano1) channels, and small conductance Ca²⁺- activated K⁺ (SK) channels. Colonic migrating motor complexes (CMMCs) and isometric force measurements were employed in control mice and PCO mice. RESULTS: PCO mice showed distended abdomen and feces excretion was significantly reduced. Anatomically, the colon above the obstructive silicone ring was obviously dilated. Kit and Ano1 proteins in the colonic smooth muscle layer of the PCO colons were significantly decreased, while the expression of Pdgfra and SK3 proteins were significantly increased. The effects of a nitric oxide synthase inhibitor (L-NAME) and an Ano1 channel inhibitor (NPPB) on CMMC and colonic spontaneous contractions were decreased in the proximal and distal colons of PCO mice. The SK agonist, CyPPA and antagonist, apamin in PCO mice showed more effect to the CMMCs and colonic smooth muscle contractions. CONCLUSIONS: Colonic transit disorder may be due to the downregulation of the Kit and Ano1 channels and the upregulation of SK3 channels in platelet-derived growth factor receptor-α positive (PDGFRα⁺) cells. The imbalance between interstitial cells of Cajal-Ano1 and PDGFRα-SK3 distribution might be a potential reason for the colonic dysmotility.

Colonic Transit Disorder Mediated by Downregulation of Interstitial Cells of Cajal/Anoctamin-1 in Dextran Sodium Sulfate-induced Colitis Mice

BACKGROUND/AIMS: Interstitial cells of Cajal (ICC) and their special calcium-activated chloride channel, anoctamin-1 (ANO1) play pivotal roles in regulating colonic transit. This study is designed to investigate the role of ICC and the ANO1 channel in colonic transit disorder in dextran sodium sulfate (DSS)-treated colitis mice. METHODS: Colonic transit experiment, colonic migrating motor complexes (CMMCs), smooth muscle spontaneous contractile experiments, intracellular electrical recordings, western blotting analysis, and quantitative polymerase chain reaction were applied in this study. RESULTS: The mRNA and protein expressions of c-KIT and ANO1 channels were significantly decreased in the colons of DSS-colitis mice. The colonic artificial fecal-pellet transit experiment in vitro was significantly delayed in DSS-colitis mice. The CMMCs and smooth muscle spontaneous contractions were significantly decreased by 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), an ANO1 channel blocker, and NG-Nitro-L-arginine methyl ester hydrochloride (L-NAME), an inhibitor of nitric oxide synthase activity, in DSS-colitis mice compared with that of control mice. Intracellular electrical recordings showed that the amplitude of NPPB-induced hyperpolarization was more positive in DSS-colitis mice. The electric field stimulation-elicited nitric-dependent slow inhibitory junctional potentials were also more positive in DSS-colitis mice than those of control mice. CONCLUSION: The results suggest that colonic transit disorder is mediated via downregulation of the nitric oxide/ICC/ANO1 signalling pathway in DSS-colitis mice.