Aim To investigate the effects of L-argi-nine on spontaneous contraction of rat colon and the relative mechanisms.Methods An organ bath system was use to measure the spontaneous contraction of both longitudinal smooth muscle strips(LMS)and circular muscle strips(CMS).Whole-cell voltage-clamp tech-niques were applied to observe the alterations in cur-rents of L-type voltage-dependent Ca2+channels(VD-CCs),and voltage-gated K+channel(Kv)in single smooth muscle cells(SMCs)from rat colon.Results L-Arginine(1 mmol·L-1)significantly enhanced the spontaneous contraction of both LMS and CMS.The excitatory response to L-arginine was remarkably attenuated by tetrodotoxin(1 mmol·L-1)and atro-pine(1 mmol·L-1),antagonist of muscarinic ACh receptor(mAChR).However,the inhibitor of nitric oxide(NO)synthesis L-NNA(1 mmol·L-1)failed to block the action of L-Arginine.Furthermore,whole-cell patch-clamp recordings showed that L-arginine ac-tivated VDCCs and inhibited Kv channels on SMCs.Conclusions L-Arginine exerts an excitatory effect on colonic motility in a nitric oxide(NO)-independent manner and the stimulatory action of L-arginine is part-ly mediated by mAChR.In addition,VDCCs and Kv channels are both involved in L-arginine-induced exci-tation.

Objective:Using cancer care as an example,we apply multi-dimensional data for healthcare region division in Beijing,and apply indicators to compare the results of the divisions.Methods:We use two approaches:the hospital catchments division method based on the hospital service range,and the K-Means clustering algorithm based on the population geographic distribution from the residents'healthcare needs,and established two indicators for comparison.Results:Three regions are divided by hospital service range method and eight regions by population geographic distribution method.The indicators of the number of beds per 100 000 population and the need satisfaction rate are more balanced among the different regions than when divided by administrative district.Conclusions:The distribution of healthcare resource in Beijing is significantly imbalanced.The region division based on hospital service range has extended the range of high-quality medical institutions.The division based on population geographical distribution reflects the actual supply and need of healthcare resources in different regions.Beijing can adopt the regional division method based on hospital service range to expand the service coverage of high-quality hospitals and reduce the imbalance in medical resources between central urban areas and suburban areas.The regional division based on population geographical distribution can provide decision support to achieve balanced allocation of healthcare resources.

Objective:To examine the factors that contribute to memory impairment in elderly stroke patients and develop a predictive model.Methods:One hundred stroke patients from the First People's Hospital of Changzhou were selected to assess the incidence of memory impairment using the Montreal cognitive assessment memory index score(MoCA-MIS).Univariate analysis and multivariate Logistic regression were performed to determine the factors influencing memory impairment in these patients.Additionally, the correlation among relevant scale scores was examined, and a prediction model was developed.Results:In the study, 49 patients(49.0%)did not exhibit memory impairment.Patients with memory impairment were found to have higher proportions of individuals over 75 years old, elevated levels of triglyceride(TG), total cholesterol(TC), low-density lipoproteins cholesterol(LDL-C), and National Institute of Health Stroke Scale(NIHSS)scores compared to those without memory impairment.Conversely, patients without memory impairment had higher proportions of individuals with more than 9 years of education, higher levels of high-density lipoprotein cholesterol(HDL-C), mini-mental state examination(MMSE)scores, Rivermead behavioural memory test-Ⅱ(RBMT-Ⅱ)scores, and picture-based memory impairment screen(PMIS)scores(all P<0.05).Furthermore, Montreal cognitive assessment-memory index(MoCA-MIS)scores in stroke patients with memory impairment showed negative correlations with NIHSS scores, TG, and LDL-C, while showing positive correlations with HDL-C, MMSE scores, RBMT-Ⅱ scores, and PMIS scores(all P<0.05).Multifactorial Logistic regression analysis indicated that years of education, TG, HDL-C, NIHSS score, MMSE score, RBMT-Ⅱ score, PMIS score, and the location of the lesion in the cortex or temporal lobe were significant factors influencing memory impairment in stroke patients(all P<0.05).The receiver operating characteristic curve(ROC)analysis revealed an area under curve(AUC)of 0.955(95% CI: 0.921-0.977)for the prediction model of memory impairment in stroke patients, with a Yoden index of 0.841. Conclusions:The risk of memory impairment in stroke patients is associated with education years and blood lipid levels.Factors such as high education level, active cognitive function, and memory training serve as protective factors against memory impairment.The prediction model developed using these influencing factors demonstrates high predictive accuracy for post-stroke memory impairment.

Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

OBJECTIVE To study the pharmacokinetic changes in the plasma and cerebrospinal fluid of bronchial asthma model rats after the complication of Ephedra sinica and Prunus armeniaca. METHODS SD male rats were randomly divided into blank group， model group， E. sinica group （12 g/kg， calculated by raw drug， similarly hereinafter）， P. armeniaca group （6 g/kg） and E. sinica-P. armeniaca drug-pair group （12 g/kg of E. sinica+6 g/kg of P. armeniaca）， with 6 rats in each group. Except for the blank group， the bronchial asthma model was induced by spraying rats in each group with an equal volume mixture of 2% acetylcholine chloride and 0.4% histamine phosphate， once a day， for 7 d. One hour before modeling every time， rats in each group were gavaged with the corresponding drug/normal saline， once a day， for 7 d. After the final administration and provocation of asthma， blood and cerebrospinal fluid collection were performed at different time points. The plasma and cerebrospinal fluid samples were pre-treated （with geranylgeranyl as the internal standard）， and the mass concentrations of ephedrine/pseudoephedrine， methyl ephedrine and amygdalin in both samples were determined by liquid chromatography-tandem mass spectrometry. DAS 2.0 pharmacokinetic software was used to determine the main pharmacokinetic parameters through the non-atrial chamber model and to compare the changes of the pharmacokinetic parameters before and after the combination of the two drugs. RESULTS Compared with E. sinica group， cmax and AUC0-21.33 h （or AUC0-10.67 h） of ephedrine/pseudoephedrine and methyl ephedrine in the plasma and cerebrospinal fluid of rats were significantly reduced in E. sinica-P. armeniaca drug-pair group， while CLZ/F and VZ/F were significantly increased （P＜0.05 or P＜0.01）； tmax of methyl ephedrine in the cerebrospinal fluid was significantly shortened （P＜ 0.05）.Compared with P. armeniaca group， the t1/2 of amygdalin in the plasma of rats in E. sinica-P. armeniaca drug-pair group was significantly shortened， and CLZ/F was significantly increased （P＜0.01）； the tmax of bitter amygdalin in the cerebrospinal fluid was significantly shortened， and the AUC0-10.67 h， CLZ/F， and VZ/F were significantly increased （P＜0.01）. CONCLUSIONS The combination of E. sinica and P. armeniaca accelerates the absorption and elimination of ephedra alkaloids， thus reducing the accumulation of ephedra alkaloids in the bronchial asthma model rats.

This study collected epidemic data of COVID-19 in Zhengzhou from January 1 to January 20 in 2022. The epidemiological characteristics of the local epidemic in Zhengzhou High-tech Zone caused by the SARS-CoV-2 Delta variant were analyzed through epidemiological survey and big data analysis, which could provide a scientific basis for the prevention and control of the Delta variant. In detail, a total of 276 close contacts and 599 secondary close contacts were found in this study. The attack rate of close contacts and secondary close contacts was 5.43% (15/276) and 0.17% (1/599), respectively. There were 10 confirmed cases associated with the chain of transmission. Among them, the attack rates in close contacts of the first, second, third, fourth and fifth generation cases were 20.00% (5/25), 17.86% (5/28), 0.72% (1/139) and 14.81% (4/27), 0 (0/57), respectively. The attack rates in close contacts after sharing rooms/beds, having meals, having neighbor contacts, sharing vehicles with the patients, having same space contacts, and having work contacts were 26.67%, 9.10%, 8.33%, 4.55%, 1.43%, and 0 respectively. Collectively, the local epidemic situation in Zhengzhou High-tech Zone has an obvious family cluster. Prevention and control work should focus on decreasing family clusters of cases and community transmission.
Humans ; SARS-CoV-2 ; COVID-19 ; Epidemics ; Incidence

Diabetic wounds are a common complication of diabetic patients, and the incidence has been increasing in recent years. In addition, its poor clinical prognosis seriously affects the quality of life of patients, which has become the focus and difficulty of diabetes treatment. As the RNA regulating gene expression, non-coding RNA can regulate the pathophysiological process of diseases, and play an important role in the healing process of diabetic wounds. In this paper, we reviewed the regulatory role, diagnostic value, and therapeutic potential of three common non-coding RNA in diabetic wounds, in order to provide a new solution for the diagnosis and treatment of diabetic wounds at the genetic and molecular level.
Humans ; Quality of Life ; Diabetes Mellitus/genetics* ; Wound Healing ; RNA, Untranslated/genetics*

During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.

To investigate the crucial role of particle size in the biological effects of nanoparticles, a series of mesoporous silica nanoparticles (MSNs) were prepared with particle size gradients (50, 100, 150, 200 nm) with the traditional Stober method and adjusting the type and ratio of the silica source. The correlation between toxicity and size-caused biological effects were then further examined both in vitro and in vivo. The results indicated that the prepared MSNs had a uniform size, good dispersal, and ordered mesoporous structure. Hemolytic toxicity was found to be independent of particle size. At the cellular level, MSNs with smaller particle sizes were more readily internalized by cells, which initiated to more intense oxidative stress, therefor inducing higher cytotoxicity, and apoptosis rate. In vivo studies demonstrated that MSNs primarily accumulated in the liver and kidneys of mice. Pharmacokinetic analysis revealed that larger MSNs were eliminated more efficiently by the urinary system than smaller MSNs. The mice's body weight monitoring, blood tests, and pathological sections of major organs indicated good biocompatibility for MSNs of different sizes. Animal welfare and the animal experimental protocols were strictly consistent with related ethics regulations of Zhejiang Chinese Medical University. Overall, this study prepared MSNs with a particle size gradient to investigate the correlation between toxicity and particle size using macrophages and endothelial cells. The study also examined the biosafety of MSNs with different particle sizes in vivo and in vitro, which could help to improve the safety design strategy of MSNs for drug delivery systems.