ObjectiveTo research the mechanism underlying the effect of raw and processed Aurantii Fructus Immaturus switched to Zhishi Shaoyaosan （ZSS） on constipation-predominant irritable bowel syndrome （C-IBS） rats via the brain-gut-microbiota axis. MethodEighty rats were randomly divided into the blank， model， positive drug （pinaverium bromide， 15.625 mg·kg^-1）， raw ZSS， stir-fried ZSS， bran-fried ZSS， charcoal-fried ZSS and finished ZSS groups （3.75 g·kg^-1）， with 10 rats in each group. Except for the blank group， which received intragastric administration of 0.9% sodium chloride solution at room temperature， all other groups were administered the ice solution at 0 to 4 ℃ （2 mL·d^-1， for a total of 14 d） to establish the C-IBS rat model. The fecal water content and the propulsion rate of small intestine were detected after 14 d of continuous drug administration. The levels of 5-hydroxytryptamine （5-HT）， vasoactive intestinal peptide （VIP）， neuro-peptide Y （NPY）， calcitonin gene-related peptide （CGRP）， substance P （SP）， diamine oxidase （DAO） and D-lactic acid （D-LA） were detected by enzyme linked immunosorbent assay （ELISA）. Hematoxylin-eosin （HE） staining was used to observe the changes in colonic pathological injury in each group. The expression levels of cyclic adenosine monophosphate （cAMP）， protein kinase A （PKA） and aquaporin-3 （AQP3） mRNA in colon tissues were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and the protein expressions of VIP and AQP3 in colon tissues were detected by Western blot. The content of short chain fatty acids （SCFAs） was determined by gas chromatography-mass spectrometry. ResultCompared with the blank group， the fecal water content and intestinal propulsion rate of rat in the model group were significantly decreased （P<0.01）， and the levels of 5-HT， VIP， CGRP and SP in serum were significantly increased. Simultaneously， the NPY levels significantly decreased （P<0.01）， the levels of DAO and D-LA in plasma were significantly increased （P<0.01）， and the mucosal epithelium of colon tissue was slightly damaged， with reduced goblet cells and significantly reduced luminal granules. The mRNA expression levels of AQP3， cAMP and PKA and the protein expression levels of AQP3 and VIP in colon tissue were significantly decreased （P<0.05， P<0.01）. The total amount of SCFAs in feces showed an obvious decreasing trend， with the contents of acetic acid， isobutyric acid， isovaleric acid， valeric acid and caproic acid decreased significantly， while the contents of propionic acid and butyric acid increased significantly （P<0.05， P<0.01）. Compared with the model group， the treatment groups increased the intestinal propulsion rate， improved the intestinal mucosal barrier function， and adjusted the level of serum brain-gut peptide in C-IBS rats （P<0.05， P<0.01）. The expression levels of AQP3， cAMP， PKA mRNA and VIP， AQP3 protein in colon tissue of rats in all treatment groups were increased. All the treatment groups had a significant downregulation of the content of SCFAs except for isobutyric acid in rat feces， and the effect of ZSS prepared by the bran-fried Aurantii Fructus Immaturus was superior than that of other ZSS. ConclusionThe raw and processed Aurantii Fructus Immaturus switched to ZSS could influence the brain-gut-microbiota axis to treat C-IBS rats and it is more reasonable to use bran-fried Aurantii Fructus Immaturus in ZSS.

Sleep deprivation (SD) has a profound impact on the central nervous system, resulting in an array of mood disorders, including depression and anxiety. Despite this, the dynamic alterations in neuronal activity during sleep deprivation have not been extensively investigated. While some researchers propose that sleep deprivation diminishes neuronal activity, thereby leading to depression. Others argue that short-term sleep deprivation enhances neuronal activity and dendritic spine density, potentially yielding antidepressant effects. In this study, a two-photon microscope was utilized to examine the calcium transients of anterior cingulate cortex (ACC) neurons in awake SD mice in vivo at 24-hour intervals. It was observed that SD reduced the frequency and amplitude of Ca2+ transients while increasing the proportions of inactive neurons. Following the cessation of sleep deprivation, neuronal calcium transients demonstrated a gradual recovery. Moreover, whole-cell patch-clamp recordings revealed a significant decrease in the frequency of spontaneous excitatory post-synaptic current (sEPSC) after SD. The investigation also assessed several oxidative stress parameters, finding that sleep deprivation substantially elevated the level of malondialdehyde (MDA), while simultaneously decreasing the expression of Nuclear Factor erythroid 2-Related Factor 2 (Nrf2) and activities of Superoxide dismutase (SOD) in the ACC. Importantly, the administration of gallic acid (GA) notably mitigated the decline of calcium transients in ACC neurons. GA was also shown to alleviate oxidative stress in the brain and improve cognitive impairment caused by sleep deprivation. These findings indicate that the calcium transients of ACC neurons experience a continuous decline during sleep deprivation, a process that is reversible. GA may serve as a potential candidate agent for the prevention and treatment of cognitive impairment induced by sleep deprivation.

Objective: This study’s objective is to assess the efficacy and safety of Pulsed Magnetic Therapy System (PMTS) in improving insomnia disorder. Methods: Participants with insomnia disorder were randomly assigned to receive either PMTS or sham treatment for four weeks (n= 153; PMTS: 76, sham: 77). Primary outcomes are the Insomnia Severity Index (ISI) scores at week 0 (baseline), 1, 2, 3, 4 (treatment), and 5 (follow-up). Secondary outcomes are the Pittsburgh Sleep Quality Index at baseline and week 4, and weekly sleep diary-derived values for sleep latency, sleep efficiency, real sleep time, waking after sleep onset, and sleep duration. Results: The ISI scores of the PMTS group and the sham group were 7.13±0.50, 11.07±0.51 at week 4, respectively. There was a significant group×time interaction for ISI (F3.214, 485.271=24.25, p<0.001, ηp 2=0.138). Only the PMTS group experienced continuous improvement throughout the study; in contrast, the sham group only experienced a modest improvement after the first week of therapy. At the end of the treatment and one week after it, the response of the PMTS group were 69.7% (95% confidence interval [CI]: 58.6%–79.0%), 75.0% (95% CI: 64.1%–83.4%), respectively, which were higher than the response of the sham group (p<0.001). For each of the secondary outcomes, similar group×time interactions were discovered. The effects of the treatment persisted for at least a week. Conclusion PMTS is safe and effective in improving insomnia disorders.

Liposomes have made remarkable achievements as drug delivery vehicles in the clinic. Liposomal products mostly benefited from remote drug loading techniques that succeeded in amphipathic and/or ionizable drugs, but seemed impracticable for nonionizable and poorly water-soluble therapeutic agents, thereby impeding extensive promising drugs to hitchhike liposomal vehicles for disease therapy. In this study, a series of weak acid drug derivatives were designed by a simplistic one step synthesis, which could be remotely loaded into liposomes by pH gradient method. Cabazitaxel (CTX) weak acid derivatives were selected to evaluate regarding its safety profiles, pharmacodynamics, and pharmacokinetics. CTX weak acid derivative liposomes were superior to Jevtana® in terms of safety profiles, including systemic toxicity, hematological toxicity, and potential central nerve toxicity. Specifically, it was demonstrated that liposomes had capacity to weaken potential toxicity of CTX on cortex and hippocampus neurons. Significant advantages of CTX weak acid derivative-loaded liposomes were achieved in prostate cancer and metastatic cancer therapy resulting from higher safety and elevated tolerated doses.

Objective:To analyze the research status and discuss hot topics and development trends of studies on clinical nutrition in congenital heart disease (CHD) at home and abroad, so as to provide reference for Chinese researchers.Method:Studies on clinical nutrition in CHD were retrieved from the databases of CNKI and Web of Science, from the founding of database until 2020. CiteSpace 5.6.R5 was used for visual analysis of authors, countries, institutions, research hotspots and frontiers.Results:A total of 163 Chinese and 1,809 English publications were included. The number of literatures published at home and abroad shows an overall trend of growth. The United States has the largest number of publications, with China in seventh place. Domestic publishing institutions are mainly hospitals, led by Nanjing Children's Hospital affiliated to Nanjing Medical University. Foreign publications are mainly by university institutions, with Harvard University in the United States ranking first. Research teams led by authors including Gu Ying and Ravishankar C. are at the core in this field. The most discussed issues in China are mainly nutritional risk, nutritional support and nutrient research. The main target populations are ICU patients, premature infants, infants and children, etc. The forefront of research includes early enteral nutrition, prognosis and feeding intolerance. In foreign countries, studies mainly focus on epidemiology, nutritional support, malnutrition, risk factors, nutritional treatment, energy metabolism, obesity, clinical outcomes, etc. Main target population is special population, such as neonates with CHD, infants, children, patients after heart transplantation, etc. cohort studies and researches on overweight are at the frontier.Conclusions:The research on nutrition in CHD has attracted more and more attention. There are some differences in research content and hot topics between domestic and foreign studies. Therefore, we should strengthen the cooperation and exchanges among institutions, combine the advantages of CHD nutrition research in China, and strengthen the epidemiological study of CHD nutrition and the nutrition management of CHD key population, so as to further promote research development in this field.

Objective: To explore the clinical value of new rapid pathological diagnosis technology in the examination of cervical lesions in primary medical institution. Methods: In the Affiliated Hospital of Yangzhou University, 25 cases of cervical scraping and 22 cases of cervical biopsy were selected.Twenty-five cases of cervical scraping scraped two wipers during operation, the results were compared with conventional pathological techniques and new rapid pathological diagnosis techniques.Twenty-two cases of cervical biopsy used a new rapid pathological diagnosis technique to perform cytological diagnosis of biopsy tissue rolls in biopsy operation.According to the results of rapid pathological diagnosis, the biopsy operation plan was adjusted to analyze the clinical value of the new rapid pathological diagnosis technique in cervical lesions in primary medical institution. Results: The new rapid pathological diagnosis technology required less space and no pollution, and the diagnosis took about 2-3 min, which did not affect the normal inspection operation.Twenty-five cases of cervical scraping were produced with new rapid pathological diagnosis technique, and the quality of cervical scraping produced with conventional pathological technique was consistent, which could satisfy the needs of pathological cytological diagnosis; twenty-two cases of cervical biopsy under the vaginal device were assisted by this technology and it could increase the positive rate of the first biopsy. Conclusion Cervical scraping and cervical biopsy are still the main methods for cervical lesions examination in primary hospitals.The new rapid pathological diagnosis technology can provide the real-time pathological diagnosis of cervical scraping, improve the positive detection rate of the first biopsy of cervical biopsy, and the cost is low, suitable for promotion in primary medical institution.

Background and purpose:Alpha fetoprotein (AFP)-producing gastric cancer (AFPGC) is considered to be a special type of gastric cancer. Currently, the effect on AFPGC is not as good as the common AFP-
negative gastric cancer. Therefore, it is very important to explore clinicopathological features of AFPGC cancer, to improve diagnosis and individualized treatment. This study is to investigate the expressions of hepatocyte growth factor receptor c (c-Met), vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER-2) in the AFPGC.Methods:A total number of 44 cases of AFPGC (serum AFP≥10 μg/L) tissues were selected as a test group. There were 30 cases of serum AFP≥200 μg/L. This study collected 30 cases of gastric cancer with normal AFP and 30 cases of hepatocellular carcinoma with increased AFP (serum AFP≥200 μg/L) as 2 control groups. The cases of the 3 groups had the same clinical stage basically. The expressions of c-Met, VEGF, EGFR and HER-2, CD34 were detected by immunohistochemistry (EnVision staining method). Tumor microvessel density (MVD) was calculated by marking CD34, and the results were analyzed. The clinicopathologic parameters were recorded accurately: gender, age, highest level of serum AFP, tumor differentiation, tumor stage, tumor location, lymph node metastasis, liver metastasis, Lauren classiifcation, etc. These patients were followed up regularly. The clinical pathological features of AFPGC patients were investigated.Results:AFPGC clinical characteristics showed that, among 44 cases of AFPGC group, 86.36% (38/44) had lymph node metastasis, 54.55% (24/44) had hepatic metastasis, intestinal type was 36.36% (16/44), diffuse type was 56.82% (25/44), mixed type was 6.82% (3/44). The positive expression rates of c-Met protein in AFPGC, gastric cancer with normal AFP, hepatocellular carcinoma with increased AFP were 73.33% (22/30), 70.00% (21/30) and 53.33% (16/30), respectively. The positive expression rates of VEGF protein were 76.67% (23/30), 56.67% (17/30) and 66.67% (20/30), respectively. The positive expression rates of EGFR protein were 53.33% (16/30), 40.00% (12/30) and 73.33% (22/30), respectively. The “++ and +++” expression rates of HER-2 in AFPGC, gastric cancer with normal AFP and hepatocellular carcinoma with increased AFP were 38.64% (17/44), 23.33% (7/30) and 26.67% (7/30), respectively. The MVD values in AFPGC, gastric cancer with normal AFP and hepatocellular carcinoma with increased AFP were 23.03±10.24, 21.92±11.45 and 19.43±7.83, respectively. Compared with gastric cancer with normal AFP, expression of VEGF protein was signiifcantly higher in the AFPGC (P<0.05). Compared with hepatocellular carcinoma with increased AFP, the expression of c-Met protein was significantly higher in AFPGC (P<0.05).Conclusion:AFPGC is prone to lymph node metastasis and hepatic metastasis. The major part is the diffuse type in Lauren classiifcation. The positive expression rates of VEGF protein in AFPGC were signiifcantly higher than the gastric cancer with normal AFP. The positive expression rates of c-Met protein in AFPGC were signiifcantly higher than the hepatocellular carcinoma with AFP increased.

Objective To investigate the role of lymph vessel density (LVD) and microvessel pericyte coverage index (MPI) in the pathogenesis of nasal polyps.Methods Using immunohistochemistry and immunofluorescence double staining method,the expressions of albumin,D2-40 and CD34-α-SMA in 11 specimens of normal nasal mucosa,26 specimens of nasal polyp and 26 specimens of inferior turbinate tissue from patients with nasal polyps were investigated.The counts of microvessel density (MVD),lymph vessel density (LVD) and microvessel pericyte coverage index (MPI) were compared.SPSS 17.0 software was used to analyze the data.Results The nasal polyp group(0.269 ±0.096) had more albumin than inferior turbinate tissue group (0.159 ± 0.078) and normal nasal mucosa group (0.138 ± 0.045),the differences were significant (q value was 4.873,4.446,both P ＜ 0.05).The counts of MVD in nasal polyp group (30.52 ± 4.42) were not significantly higher than those in inferior turbinate tissue group (30.33 ± 6.03) and normal nasal mucosa group(28.21 ±6.84),the differences were not significant (q value was 0.130,1.147,both P ＞0.05).The MPI in nasal polyp group (0.291 ±0.096) was significantly lower than those in inferior turbinate tissue group(0.432 ± 0.101) and normal nasal mucosa group(0.416 ± 0.071),the difference was significant (q value was 5.399,3.680,both P ＜ 0.05).The counts of LVD in the nasal polyp group (0.245 ± 0.073) were significantly lower than those in inferior turbinate tissue group (0.431 ± 0.054) and normal nasal mucosa group (0.470 ± 0.078),the difference was significant (q value was 10.004,9.328,both P ＜ 0.05).MPI expression in the nasal polyp group was negetively correlated to albumin expression(r =-0.889,P ＜ 0.05).The LVD expression in the nasal polyp group was negetively correlated to albumin expression(r =-0.901,P ＜ 0.05).Conclusion Different LVD and MIP in nasal polyp tissues and normal nasal mucosa tissues imply that microcirculatory dysfunction plays a crucial role in the pathogenesis of nasal polyps.

OBJECTIVE:To compare the differences in the contents of water-soluble total protein,total phenolic acid and total polysaccharides among the water decoctions of crude Cibotium barometz and processed products and to illuminate the effect of pro-cessing on 3 kinds of components of C. barometz. METHODS:UV-visible spectrophotometry was adopted to determine the con-tents of water-soluble total protein,total phenolic acid and total polysaccharides in the water decoction of crude C. barometz and 4 processed products,namely sand-scorch C. barometz,yellow wine C. barometz,salt C. barometz and steamed C. barometz,at wavelengths of 590,760 and 489 nm respectively. RESULTS:The contents of water-soluble total protein in 5 samples were 4.03%,3.32%,3.13%,3.33% and 3.49%,those of total phenolic acid therein were 0.25%,1.34%,1.38%,2.34% and 1.41%,and those of total polysaccharides therein were 28.56%,36.06%,45.21%,49.60% and 49.01%,respectively. CONCLU-SIONS:All above processing methods have an effect to some degree on the contents of the 3 kinds of components of C. barometz, where the contents of water-soluble total protein are lower after processing,while those of total phenolic acid and total polysaccha-rides are higher thereafter.

OBJECTIVE: To investigate the efficacy and safety of Ji-Tai tablet and Ji-Tai tablet combined with buprenorphine in the treatment of patients with acute withdrawal syndrome of mild heroin dependence. METHODS: A total of 150 patients with mild heroin dependence were recruited, and were randomly assigned to a Ji-Tai tablet group (n=50), a Ji-Tai tablet combined with buprenorphine group (n=50) and a control group (n=50) during a 10-day clinical trial. Opiate withdrawal scale (OWS) was used to measure the severity of withdrawal symptoms. Anxiety symptoms assessments were made at 0 day (baseline), the day 5 (middle), and the day 10 (end) by the Hamilton anxiety scale (HAMA). Symptoms were assessed before and 1 h or 2 h after medication each day. The total withdrawal symptoms scores and the daily reduction rate were used to measure the effect of Ji-Tai tablet vs Ji- Tai tablet plus buprenorphine. Safety evaluation was carried out by the following measures: baseline of treatment, drug side effects after the treatment, vital signs (blood pressure, heart rate, and respiration rate), laboratory examination (routine blood and urine tests and the liver and kidney function tests), and electrocardiograms. RESULTS: A total of 142 mild heroin dependence patients performed the experiments (including 48 in the Ji-Tai tablet group, 48 in the Ji-Tai tablet with buprenorphine group and 46 in the control group). The scores of baseline withdrawal symptoms were 43.520±19.786, 42.640±17.648 and 47.100±24.450, respectively, with no significant differences among the 3 groups (all P>0.05 ). During the 10-day treatment, the reduction rate of acute withdrawal symptoms scores increased daily, the acute withdrawal syndrome scores and the anxiety symptoms scores declined from day 0 to day 10, there was also no significant difference among the 3 groups (all P>0.05). Ji-Tai tablet did not affect vital signs such as blood pressure, heart rate, and respiration rate. CONCLUSION Ji-Tai tablet or Ji-Tai tablet combined with buprenorphine had no effect on acute withdrawal symptoms of mild heroin dependence.
Anxiety ; Buprenorphine ; therapeutic use ; Double-Blind Method ; Drugs, Chinese Herbal ; therapeutic use ; Heroin Dependence ; drug therapy ; Humans ; Substance Withdrawal Syndrome ; drug therapy ; Tablets