Inflammatory bowel disease (IBD) is an idiopathic intestinal inflammatory condition with chronic and relapsing manifestations and is characterized by a disturbance in the interplay between the intestinal microbiota, the gut, and the brain. The microbiota-gut-brain axis involves interactions among the nervous system, the neuroendocrine system, the gut microbiota, and the host immune system. Increasing published data indicate that psychological stress exacerbates the severity of IBD due to its negative effects on the microbiota-gut-brain axis, including alterations in the stress response of the hypothalamic-pituitary-adrenal (HPA) axis, the balance between the sympathetic nervous system and vagus nerves, the homeostasis of the intestinal flora and metabolites, and normal intestinal immunity and permeability. Although the current evidence is insufficient, psychotropic agents, psychotherapies, and interventions targeting the microbiota-gut-brain axis show the potential to improve symptoms and quality of life in IBD patients. Therefore, further studies that translate recent findings into therapeutic approaches that improve both physical and psychological well-being are needed.
Humans ; Inflammatory Bowel Diseases/metabolism* ; Stress, Psychological/microbiology* ; Gastrointestinal Microbiome/physiology* ; Brain/metabolism* ; Hypothalamo-Hypophyseal System ; Pituitary-Adrenal System ; Animals

Objective:To observe the clinical efficacy and safety of Jianpi Bushen Jiedu Prescription combined with 5-fluorouracil (5-FU)-based chemotherapy and targeted therapy for the treatment of advanced colorectal cancer patients with liver and kidney yin deficiency combined with spleen deficiency pattern.Methods:A randomized controlled trial was conducted. A total of 72 hospitalized patients with advanced colorectal cancer treated at the Department of Oncology, Nanjing Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine from October 2022 to January 2024 were enrolled as study subjects. Using a random number table method, they were allocated into two groups, with 36 patients in each group. The control group received the mFOLFOX6/FOLFIRI combined with bevacizumab regimen, while the treatment group was administered additional oral Jianpi Bushen Jiedu Prescription on the basis of the control group. Two weeks was a cycle in both groups, with a total of 6 cycles of treatment. Serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), and carbohydrate antigen 724 (CA724) were detected using electrochemiluminescence; the Karnofsky Performance Status (KPS) scale was utilized to evaluate patients' functional status; vital signs were continuously monitored, and adverse reactions were recorded. The short-term efficacy and TCM syndrome efficacy of patients were evaluated.Results:The treatment group demonstrated higher objective response rate (ORR) [31.25% (10/32) vs. 21.88% (7/32), χ2=0.72] and disease control rate (DCR) [84.38% (27/32) vs. 71.88% (23/32), χ2=1.46] compared to the control group, without statistical significance ( P>0.05). Post-treatment levels of CEA [4.09 (3.31,8.57) μg/L vs. 10.07 (4.55,22.35) μg/L, Z=-2.10] and CA72-4 [4.54 (2.04,10.99) mU/L vs. 9.48 (4.34,18.95) mU/L, Z=-2.52] in the treatment group were significantly lower than those in the control group ( P<0.05). The total effective rate of TCM syndrome was significantly higher in the treatment group [78.13% (25/32)] compared with the control group [50.00% (16/32)], with statistical significance ( χ2=5.50, P=0.019). Post-treatment KPS scores in the treatment group [80.0 (80.0, 80.0) vs. 70.0 (62.5, 80.0), Z=-2.76] were significantly higher compared with the control group ( P<0.01). During the treatment period, the treatment group showed statistical significance compared with the control group in the incidence of hemoglobin decrease ( χ2=4.66), leukopenia decrease ( χ2=4.27), and peripheral neuropathy ( χ2=3.93), with statistical significance ( P<0.05). Conclusion:The addition of Jianpi Bushen Jiedu Prescription to 5-FU-based chemotherapy combined with targeted therapy demonstrates significant clinical benefits in advanced colorectal cancer patients, including reducing tumor marker levels, alleviating clinical symptoms, improving quality of life, and mitigating treatment-related toxicities, with a good safety.

In the study of kidney ischemia-reperfusion injury, rhabdomyolysis induced kidney injury, hyperuricemia induced kidney injury and other diseases, Diaphragma Juglandis Fructus extract has shown various pharmacological effects such as lowering uric acid, anti-inflammatory, anti-tumor, sedative and sedative effects. It can improve kidney function by reducing inflammatory response, inhibiting oxidative stress, regulating related enzyme activity and other mechanisms. At the same time, Diaphragma Juglandis Fructus extract also has hypoglycemic and lipid-lowering effects, which can regulate glucose and lipid metabolism, inhibit inflammatory reaction, and reduce oxidative stress. It has potential application prospects in the treatment of diabetes nephropathy. At present, current research is mostly focused on animal and cellular experiment levels. Although certain achievements have been made, further clinical research is still needed to clarify its effectiveness and safety in the human body, and to further explore the active components to promote its application in the treatment of kidney diseases in clinical practice.

OBJECTIVE To prepare a self-microemulsifying drug delivery system(SMEDDS) for the oral administration of nebivolol hydrochloride(NBH) and to conduct in vitro evaluation. METHODS The solubility of NBH was determined using various oil phases, surfactants, and co-surfactants. The composition of the blank self-microemulsifying formulation was determined using pseudo-ternary phase diagrams. A centralcomposite design-response surface method was employed to screen and optimize the formulation variables, and an excess amount of NBH raw material was incorporated to determine the drug loading capacity. RESULTS The optimized composition of the NBH-SMEDDS formulation consisted of medium-chain glycerides, capryl caproyl macrogol glycerides, and 2-(2-ethoxyethoxy) ethyl acetate at a ratio of 20∶48∶32, with a drug loading capacity of 20.05 mg. The particle size, self-emulsification time, and particle size distribution range of the formulation were in agreement with the predicted values. Dissolution testing demonstrated that the overall dissolution trend of NBH-SMEDDS in the medium was higher than that of NBH powder and NBH ordinary tablet. The stability of NBH-SMEDDS was found to be satisfactory under accelerated conditions for 1, 2, and 3 months. CONCLUSION The SMEDDS shows potential for enhancing the in vitro dissolution of NBH and demonstrates good stability.

OBJECTIVE To solve the problem of insolubility of itraconazole, improve its dissolution in vitro, and provide a reference for further industrial scale-up of the itraconazole multiparticle system. METHODS Itraconazole multiparticle system pellets were dissolved in an organic solvent and prepared in a fluidized bed by bottom spraying. Itraconazole and hydroxypropyl methylcellulose were sprayed onto the surface of the sucrose pellet core to form a uniform solid dispersion. The preparation parameters of the fluidized bed bottom spray coating were investigated by single factor method. The mass ratio of drug to carrier and core weight gain of the itraconazole multiparticle system were optimized by central composite design and response surface methodology with accumulative dissolution rate, application efficiency and adhesion rate as response values. Samples were prepared to verify the optimized prescription, the microscopic hierarchical structure of the itraconazole multiparticle system was observed by scanning electron microscope, and the solid dispersion in the itraconazole multiparticle system pellets was characterized by differential scanning calorimetry(DSC) and X-ray diffraction(XRD). The dissolution curves of itraconazole pellets and the physical mixture in 0.1 mol·L−1 HCl dissolution medium were compared to verify the solubilization effect. RESULTS Single factor method was used to determine the bottom spray coating parameters of the fluidized bed. The pumping speed was set as 3.0−5.0 mL·min−1, the atomization pressure was set as 1.5 bar, the inlet air volume was set as 110 m3·h−1, and the material temperature was set as 35 ℃. According to the central composite design and response surface methodology, the mass ratio of drug to carrier of the optimized prescription was 1∶1.5 and the core weight of the pill was 75%, and the response values reached the expected value. The result of scanning electron microscopy showed that the diameter of the itraconazole multiparticle system pellet was about 910 µm, the diameter of the sucrose pellet core was about 570 µm, the thickness of the drug loading layer was about 110 µm, and the thickness of encapsulation layer was about 11 µm. The results of DSC and XRD showed that itraconazole formed a uniform solid dispersion in the itraconazole multiparticle system pellets, which was amorphous. In the dissolution medium of 0.1 mol·L−1 HCl, the accumulative dissolution rate of the multiparticle system after 90 min was about 10 times that of the physical mixture, which showed that the solubilization effect was remarkable. CONCLUSION The dissolution of itraconazole in vitro can be significantly improved by processing itraconazole into pellets with multiparticle system and forming solid dispersion.

Objective: To investigate the status and identify the influencing factors of smoking among residents in Shaoxing City, Zhejiang Province, so as to provide insights into tobacco control. Methods: Permanent residents aged 15 to 69 years in Shaoxing City were recruited using the stratified multistage random sampling method from June to December 2022, and smoking behaviors and health literacy were collected using the National Questionnaire for Surveillance on Healthy Literacy in Chinese Residents. Factors affecting smoking were identified using a multivariable logistic regression model. Results: Totally 4 156 questionnaires were allocated, and 4 055 valid questionnaires were recovered, with an effective recovery rate of 97.57%. There were 1 899 men (46.83%), 2 073 residents in rural areas (51.12%), and 3 256 married residents (80.30%). There were 805 smokers, and the rate of smoking was 19.85%. Multivariable logistic regression analysis showed that male (OR=169.861, 95%CI: 92.335-312.481), age (25-<35 years, OR=8.768, 95%CI: 2.964-25.937; 35-<45 years, OR=9.271, 95%CI: 3.077-27.933; 45-<55 years, OR=10.467, 95%CI: 3.498-31.327; 55-<65 years, OR=8.880, 95%CI: 2.964-26.608; 65-69 years, OR=6.115, 95%CI: 1.992-18.774), marital status (divorced, OR=2.035, 95%CI: 1.260-3.287; widowed, OR=2.317, 95%CI: 1.337-4.016), educational level (illiterate or semi-literate, OR=2.724, 95%CI: 1.515-4.898; primary school, OR=2.734, 95%CI: 1.823-4.100; junior high school, OR=2.003, 95%CI: 1.423-2.820; high school/vocational high school /technical secondary school, OR=1.625, 95%CI: 1.148-2.299), self-rated health status (general, OR=0.788, 95%CI: 0.623-0.996; relatively poor, OR=0.343, 95%CI: 0.191-0.617) and lack of basic health skills (OR=1.290, 95%CI: 1.007-1.653) were associated with smoking. Conclusions The smoking rate among residents in Shaoxing City is relatively low, and might be influenced by gender, age, marital status, educational level, self-rated health status, and basic health skills.

OBJECTIVE To investigate the effect of bs-5-YHEDA iron chelating peptide combined with semaglutide on the cognitive ability and pathological characteristics of D-Gal-induced Alzheimer's disease(AD) model mice. METHODS Forty mice were randomly divided into 5 groups, namely the healthy control group, PBS group, bs-5-YHEDA iron chelating peptide group, combined treatment group and positive control group, with 8 mice in each group, half of each sex. Except for the healthy control group, D-galactose was injected to induce the AD mice model for 6 weeks. For 3 consecutive weeks starting from the 4th week, the bs-5-YHEDA iron chelating peptide group was injected with bs-5-YHEDA(1 mg·mL–1) once every other day at 200 µL in the tail vein; the bs-5-YHEDA iron chelating peptide(1 mg·mL–1) and semaglutide(25 nmol·kg–1·d–1) were given alternately once a day in the combination treatment group; the positive control group was given memantine(3.3 mg·kg–1·d–1) by gavage every other day. The healthy control group and PBS group were injected with the equal dose of PBS. At the end of treatment, the learning memory ability of mice was detected by the Morris water maze method, whole brain and whole blood were dissected, and pathological changes in hippocampal region were observed by HE staining, and Aβ expression and Tau protein phosphorylation levels were detected by immunohistochemistry, enzyme-linked immunosorbent assay and immunoblotting. RESULTS In the Morris water maze spatial exploration experiment, the differences in the number of times the mice traversed the platform, the ratio of swimming distance to the target quadrant, and the time ratio were statistically significant in each group(P<0.05); compared with the PBS group, the ratio of swimming distance to the target quadrant increased in the combined treatment group, and the differences were statistically significant(P<0.05). The results of HE staining showed that compared with the healthy control mice, the hippocampal area in the PBS group showed reduced levels of pyramidal cells, disorganized arrangement, cell edema, and deep staining of nuclei consolidation. Cellular disorganization, deep staining of nuclei and apoptosis in the hippocampus were significantly improved in each treatment group after drug treatment. Immunohistochemistry and Western blotting results showed that the Aβ expression levels and Tau protein phosphorylation levels were significantly higher in the PBS-administered mice compared with the healthy control mice, and the Aβ expression levels and Tau protein phosphorylation levels were reduced in each group after drug treatment, with statistically significant differences(P<0.01 or P<0.001 ). CONCLUSION The combination of bs-5-YHEDA iron chelating peptide and semaglutide can effectively improve the learning and memory ability and pathological characteristics of AD mice, but from the results of immunohistochemistry and immunoblotting experiments, the improvement of pathological characteristics of AD mice in the combination treatment group is not obvious compared with the single bs-5-YHEDA iron chelating peptide group, suggesting that there may be a threshold effect of our designed dual-target combination treatment on the cognitive improvement of AD mice, and the optimization and validation of the effect of multi-target combination treatment need further study.

Objective To understand the awareness status of health education projects in basic public health services among medical personnel in primary medical institutions of Shaoxing City,to analyze its influ-encing factors aiming at promoting the awareness rate of basic public health services.Methods A multi-stage sampling method was adopted.The four village and town(street)health centers were extracted from each of 6 districts and counties(city)of Shaoxing City from May to June in 2023.The medical personnel in the extrac-ted units served as the respondents and completed the questionnaire survey of health education projects in bas-ic public health services through links or scanning the two-dimensional codes.The survey results conducted the statistics and the influencing factors were analyzed.Results A total of 2 595 medical personnels participa-ted in the survey,including 1926 respondents in urban areas and 669 respondents in rural areas.There were 1565 medical personnels with the awareness of health education projects,accounting for 60.31％.The results of the multivariate logistic regression analysis showed that the awareness rate of health education projects in the females(OR=1.401,95％CI:1.167-1.682),15-＜35 years old(OR=1.223,95％CI:0.874-1.712),35-＜55 years old(OR=1.454,95％CI:1.055-2.002),health education personnels(OR=1.219,95％CI:1.017-1.461),willingness of health education work(OR=1.647,95％CI:1.261-2.152)and participating in the health education training(OR=1.421,95％CI:1.185-1.705)was higher than that in the males,≥55 years old,non-health education personnel,no willingness to work in health education and not participating in health education training(P＜0.05).Conclusion The awareness rate of basic public health service health ed-ucation project is not high in Shaoxing City,and intervention should be carried out according to the influencing factors.

Purpose To design PCR combined probes u-sing TaqMan technology to detect the expression of major driver genes in a variety of soft tissue sarcomas at one time,and to dis-cuss whether the combined probes can better assist clinicopatho-logical diagnosis based on histological features and FISH results.Methods Our research group designed 32 pairs of fusion gene probes related to soft tissue sarcoma based on TaqMan tech-nique,involving 10 types of sarcoma.The histopathological specimens of 70 patients with common fusion gene soft tissue sarcoma in our hospital were examined by fusion gene combina-tion,and the histopathological specimens of 30 patients with oth-er soft tissue sarcoma without fusion gene were set as controls.Individual common sarcoma types were analyzed with FISH probe detection.At the same time,the detection performance of the combined probe was evaluated by various methods.Results The soft tissue sarcoma-related fusion gene probe designed by our research group was used to detect the confirmed soft tissue sarcomas,and the results showed that the highest sensitivity was 100％.Among the three types of tumors,protuberant dermatofi-brosarcoma,synovial sarcoma and mucinous liposarcoma were verified by FISH,and the coincidence rate of the two methods was high,with no statistical significance(P＞0.05).The re-sults of interlot and intralot reproducibility of protuberous derma-tofibrosarcoma,mucinous liposarcoma and synovial sarcoma were consistent.Three different concentration limits were used to de-tect the positive plasmid of all the fused gene RNA,and 25 cop-ies/μL was the lowest concentration limit.Conclusion Com-bined with the pathological diagnosis results,TaqMan technology can be used to design PCR combined probes for soft tissue sarco-ma,which have high sensitivity and high specificity and good methodological performance,and meet the needs of primary medical institutions for one-time and rapid auxiliary pathological diagnosis of common soft tissue sarcoma.It provides a rapid and reliable method for the detection of multiple fusion genes in clin-ical soft tissue sarcoma.

A novel amide alkaloid,bursatamide A(1),featuring an unprecedented propyl-hexahydronaphthalene carbon frame-work,was isolated from the infrequently studied sea hare Bursatella leachi,alongside a new 3-phenoxypropanenitrile alkaloid,bursatellin B(2),and twelve known compounds.The structures of 1 and 2 were elucidated through comprehensive spectroscopic data analyses,while their relative and absolute configurations(ACs)were established through total synthesis and a series of quantum chem-ical calculations,including calculated electronic circular dichroism(ECD)spectra,optical rotatory dispersion(ORD)methods,and DP4+probability analyses.Bursatamide A(1)demonstrated inhibitory effects against the human pathogenic bacteria Listeria monocyt-ogenes and Vibrio cholerae.Erythro-bursatellin B(21),a diastereoisomer of 2,exhibited notable antibacterial activity against the fish pathogenic bacterium Streptococcus parauberis FP KSP28,with an MIC90 value of 0.0472 μg·mL-1.