This study aims to investigate the effect of Chaijin Jieyu Anshen Formula on the neuroinflammation of rats with insomnia complicated with depression through the regulation of triggering receptor expressed on myeloid cells 2(TREM2)/complement protein C1q signaling pathway. Rats were randomly divided into a normal group, a model group, a positive drug group, as well as a high, medium, and low-dose groups of Chaijin Jieyu Anshen Formula, with 10 rats in each group. Except for the normal group, the other groups were injected with p-chlorophenylalanine and exposed to chronic unpredictable mild stress to establish the rat model of insomnia complicated with depression. The sucrose preference experiment, open field experiment, and water maze test were performed to evaluate the depression in rats. Enzyme-linked immunosorbent assay was employed to detect serum 5-hydroxytryptamine(5-HT), dopamine(DA), and norepinephrine(NE) levels. Hematoxylin and eosin staining and Nissl staining were used to observe the damage in nucleus accumbens neurons. Western blot and immunofluorescence were performed to detect TREM2, C1q, postsynaptic density 95(PSD-95), and synaptophysin 1(SYN1) expressions in rat nucleus accumbens, respectively. Golgi-Cox staining was utilized to observe the synaptic spine density of nucleus accumbens neurons. The results show that, compared with the model group, Chaijin Jieyu Anshen Formula can significantly increase the sucrose preference as well as the distance and number of voluntary activities, shorten the immobility time in forced swimming test and the successful incubation period of positioning navigation, and prolong the stay time of space exploration in the target quadrant test. The serum 5-HT, DA, and NE contents in the model group are significantly lower than those in the normal group, with the above contents significantly increased after the intervention of Chaijin Jieyu Anshen Formula. In addition, Chaijin Jieyu Anshen Formula can alleviate pathological damages such as swelling and loose arrangement of tissue cells in the nucleus accumbens, while increasing the Nissl body numbers. Chaijin Jieyu Anshen Formula can improve synaptic damage in the nucleus accumbens and increase the synaptic spine density. Compared to the normal group, the expression of C1q protein was significantly higher in the model group, while the expression of TREM2 protein was significantly lower. Compared to the model group, the intervention with Chaijin Jieyu Anshen Formula significantly downregulated the expression of C1q protein and significantly upregulated the expression of TREM2. Compared with the model group, the PSD-95 and SYN1 fluorescence intensity is significantly increased in the groups receiving different doses of Chaijin Jieyu Anshen Formula. In summary, Chaijin Jieyu Anshen Formula can reduce the C1q protein expression, relieve the TREM2 inhibition, and promote the synapse-related proteins PSD-95 and SNY1 expression. Chaijin Jieyu Anshen Formula improves synaptic injury of the nucleus accumbens neurons, thereby treating insomnia complicated with depression.
Animals ; Male ; Rats ; Nucleus Accumbens/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Depression/complications* ; Membrane Glycoproteins/genetics* ; Rats, Sprague-Dawley ; Sleep Initiation and Maintenance Disorders/complications* ; Neurons/metabolism* ; Receptors, Immunologic/genetics* ; Signal Transduction/drug effects* ; Synapses/metabolism*

Objective To evaluate the safety and efficacy of valve-in-valve transcatheter mitral valve replacement(ViV-TMVR)in patients with bioprosthetic valve degeneration who are at high surgical risk.Methods This study is a multi-center,retrospective cohort analysis of 20 consecutive patients who underwent transseptal ViV-TMVR using the Edwards SAPIEN 3 transcatheter heart valve(THV).The primary endpoints include technical success and procedural success,both defined according to the Mitral Valve Academic Research Consortium(MVARC)criteria,as well as mortality and functional change assessed based on New York Heart Association(NYHA)classification at 30-days and six months post-procedure.Clinical follow-up assessments are conducted at 30-days and six months.Results From February 2021 to October 2022,a total of 20 patients with symptoms of bioprosthetic valve degeneration were enrolled across nine sites in China.The patients had a mean age of(73.5±5.5)years,with 85.0％being females and 70.0％classified as NYHA class Ⅲ/Ⅳ.The study achieved a 100.0％technical success rate and a 90.0％procedural success rate finally.All patients remained alive during the 30-day follow-up period.However,six months post-intervention,two patients(10.0％)were re-hospitalized due to heart failure,and sadly,one of them(5.0％)died.None of the patients reported any adverse events related to ViV-TMVR during the follow-up period.Notably,there was a significant improvement in NYHA class compared to baseline(P=0.0004)at six-month follow-ups.Conclusions The transseptal ViV-TMVR technique proved to be highly successful and was associated with significant improvement in NYHA class function.These findings strongly suggest that it serves as a safe and efficient treatment alternative for high-risk patients suffering from bioprosthetic valve degeneration.

Objective To retrospectively analyze the association between metabolic factors and high-risk colorectal adenoma(CRA).Methods The medical records of patients aged 18-75 years who underwent their initial colonoscopy at Karamay Central Hospital of Xinjiang Uygur Autonomous Region from Jul 2000 to Mar 2017 were collected.The comparison between normal colonoscopy(NC)and high-risk CRA patients was conducted using an unpaired t-test,while chi-square test was used for categorical variables.Least absolute shrinkage and selection operator(LASSO)regression and Logistic regression were utilized to analyze the association between metabolic factors and high-risk CRA.Results A total of 1 798 patients meeting the inclusion and exclusion criteria were enrolled and divided into normal colonoscopy(NC)findings group(n=972)and high-risk CRA group(n=826).The high-risk CRA group exhibited significantly lower levels of high-density lipoprotein cholesterol(HDL-C)in comparison to the NC group,while uric acid and fibrosis 4(FIB-4)index levels were significantly higher than those observed in the NC group(all P<0.05).Based on LASSO regression analysis,we identified 12 variables that potentially influence the occurrence of high-risk CRA,including age,gender,smoking history,alcohol consumption history,non-alcoholic fatty liver disease(NAFLD),hypertension,coronary artery disease,hyperglycemia,hypercholesterolemia,low levels of HDL-C,elevated alanine aminotransferase,and elevated gamma-glutamyl transferase.Multivariate analysis revealed that individuals aged over 50 years,male gender,cigarette and alcohol consumption,low HDL-C levels,history of NAFLD and hypertension were identified as independent risk factors associated with high-risk CRA(P<0.05).In addition,without or with adjusting for age,sex,smoking,and drinking history,patients with a high TG/HDL-C ratio(the ratio≥2.68)had a significantly higher risk of high-risk CRA than those with a low TG/HDL-C ratio(the ratio<2.68)[odds ratios(ORs)were1.430 and 1.235 respectively,all P<0.05)].Without or with adjusting variables,the ORs for NAFLD patients with FIB-4 index>2.67 were 1.849(P=0.466)and 1.435(P=0.707),respectively.Conclusion A significant association exists between metabolic factors and high-risk CRA.Independent risk factors for high-risk CRA include older age(≥50 years),male,smoking history,alcohol consumption history,low levels of HDL-C,and a history of NAFLD and hypertension.Individuals exhibiting a TG/HDL-C ratio exceeding 2.68 manifest a significantly heightened susceptibility to the development of high-risk CRA.Therefore,elderly males with one or more aforementioned metabolic abnormalities should be considered a priority population for colorectal screening.

Five saponins were isolated from the kernels of Momordica cochinchinensis, by macroporous resin, silica gel, ODS column chromatography, and semi preparative HPLC. Based on MS and NMR analysis, combining with alkaline hydrolysis and acid hydrolysis, their structures were identified as: gypsogenin-3-O-{β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonosyl}-28-O-β-D-xylopyranosyl (1→3)-[β-D-xylopyranosyl (1→4)]-α-L-rhamnopyranosyl (1→2)-β-D-fucopyranoside (1), quillaic acid-3-O-{β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonosyl}-28-O-β-D-xylopyranosyl (1→3)-[β-D-xylopyranosyl (1→4)]-α-L-rhamnopyranosyl (1→2)-β-D-fucopyranoside (2), gypsogenin-3-O-β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonoside sodium (3), quillaic acid-3-O-β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonoside sodium (4), 18α-quillaic acid-3-O-β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonoside (5). Compounds 1-5 were new compounds, and named as mubezhisides A, B, C, D, E, respectively. They all could obviously inhibited the growth of Candida albicans, C. parapsilosis, and C. tropicalis.

Cervi Cornu Pantotrichum is a precious animal-derived Chinese medicinal material, while there are often adulterants derived from animals not specified in the Chinese Pharmacopeia in the market, which disturbs the safety of medication. This study was conducted with the aim of strengthening the quality control of Cervi Cornu Pantotrichum and standardizing the medication. To achieve digital identification of Cervi Cornu Pantotrichum from different sources, a digital identification model was constructed based on ultra-high performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry(UHPLC-QTOF-MS~E) combined with an adaptive boosting algorithm(Adaboost). The young furred antlers of sika deer, red deer, elk, and reindeer were processed and then subjected to polypeptide analysis by UHPLC-QTOF-MS~E. Then, the mass spectral data reflecting the polypeptide information were obtained by digital quantification. Next, the key data were obtained by feature screening based on Gini index, and the digital identification model was constructed by Adaboost. The model was evaluated based on the recall rate, F_1 composite score, and accuracy. Finally, the results of identification based on the constructed digital identification model were validated. The results showed that when the Gini index was used to screen the data of top 100 characteristic polypeptides, the digital identification model based on Adaboost had the best performance, with the recall rate, F_1 composite score, and accuracy not less than 0.953. The validation analysis showed that the accuracy of the identification of the 10 batches of samples was as high as 100.0%. Therefore, based on UHPLC-QTOF-MS~E and Adaboost algorithm, the digital identification of Cervi Cornu Pantotrichum can be realized efficiently and accurately, which can provide reference for the quality control and original animal identification of Cervi Cornu Pantotrichum.
Animals ; Algorithms ; Antlers/chemistry* ; Boosting Machine Learning Algorithms ; Chromatography, High Pressure Liquid/methods* ; Deer ; Drugs, Chinese Herbal/chemistry* ; Mass Spectrometry/methods* ; Quality Control ; Reindeer ; Tandem Mass Spectrometry/methods* ; Tissue Extracts/analysis*

Current ambient mass spectrometry ionization often requires external auxiliary equipment such as high-voltage power supply,gas cylinder,and syringe pump.Moreover,the process of sample preparation is cumbersome,and the experimental operations are complex,which makes it difficult to adapt to real-time on-site detection.In this work,a novel method was proposed,in which direct sampling of raw samples,online extraction of interest analytes,and ionization of target molecules were integrated into a single unit.With the developed method,the in-situ extraction and nano-electrospray ionization for both liquid and solid raw samples were achieved.Also,a handheld ion source and its pose adjustment device were developed,and the position and angle parameters were subsequently optimized.The performance of the ionization device was tested using standard solutions of caffeine and reserpine.The limits of detection(LODs)were 0.08 μg/L and 0.14 μg/L,with relative standard deviations(RSDs)≤3.7% and≤5.6%,respectively,indicating that the device possessed high sensitivity and stability.Using this device,three different concentrations of reserpine standard solutions were continuously tested for five days.The intra-day RSDs were consistently≤4.7% and the inter-day RSDs were all≤10.3%,showing the good working stability of the device.Without any pretreatment,a rapid qualitative detection of medicinal components including astragaloside II and cycloastragenol in five traditional Chinese medicines was carried out,with RSDs≤8.0% and≤7.1%,respectively.Additionally,rapid qualitative detection of gallic acid,a medicinal component,in white peony roots,and hypaphorine as well as quercetin in cowherb seeds were carried out,with RSDs≤7.0%,≤6.4% and≤6.1%,respectively.These results demonstrated that the ionization technology and device exhibited good stability during qualitative detection of raw samples.

6-Thioguanine(6-TG)is an antineoplastic agent used in treatment of acute leukemia.However,significant interindividual variability in dosing regimens and frequent clinical manifestations of hepatotoxicity and myelosuppression as adverse effects have affected its therapeutic efficacy.Consequently,the development of rapid analytical methods for 6-TG in clinical samples,enabling continuous therapeutic drug monitoring of plasma concentrations,holds substantial significance in optimizing dosage regimens,mitigating adverse reactions,and investigating drug metabolism mechanisms.In this study,multi-tipped gold nanostars(AuNSs)were prepared.With bis-(p-sulfonylphenyl)phenylphosphine molecule as the protecting agent and internal standard molecule,the AuNSs were assembled onto a highly sensitive surface-enhanced Raman(SERS)substrate for developing a ratio-based SERS quantitative analysis method for 6-TG in serum.The AuNSs containing multiple tips and gaps exhibited strong local surface plasmon resonance effect and SERS activity,ensuring the sensitivity of the analytical method.Furthermore,the introduction of internal standard molecules could improve the reproducibility,which guaranteed this method suitable for rapid analysis of drug molecules in complex samples.Quantitative analysis of 6-TG was achieved with linear detetion range of 1.0×10?4-1.0 mmol/L.In the spiked recovery experiments of serum,the RSD was less than 5.32%,and the recoveries were 94%-104%,which proved that this method could be used for rapid quantitative determination of 6-TG in serum.This method provided a powerful tool for studying drug pharmacokinetics,which could promote the optimization of the usage methods of anti-cancer drugs,and it was expected to further enhance the clinical efficacy and safety of 6-TG,enabling it to achieve the best therapeutic effect.

Aortic regurgitation and mitral regurgitation are more common in elderly heart valve disease,and both may be present in some patients.Severe aortic regurgitation complicated with severe mitral regurgitation often requires surgical valve replacement,but in patients at high risk of surgery,the risk of perioperative mortality is significantly increased.Therefore,for such patients,minimally invasive interventions can significantly improve long-term patient outcomes while reducing surgical risk.This article report a case of transcatheter aortic valve replacement combined with transcatheter edge-to-edge repair in the treatment of severe aortic regurgitation combined with mitral valve prolapse,in order to explore new treatment ideas for similar cases.

This study was aimed at studying the drug resistance,serotypes,and molecular characteristics of Vibrio parahaemo-lyticus(VP)in Suzhou,to provide basic data for the prevention and control of VP-related diseases.Drug susceptibility testing of 177 VP strains isolated from Suzhou City in 2023 was performed with the microbroth dilution method.Virulence genes,serotypes,and multi-locus sequence typing(MLST)were analyzed on the basis of whole genome sequencing results.The drug resistance rate of 177 VP strains was highest against cefazolin(100.00%),followed by ampicillin(77.97%),and polymyxine E(63.84%),and the multiple drug resistance rate was 53.67%.In clinical isolates,O10∶K4(37.41%)was the most abundant serotype,and was followed by O3∶K6(28.78%),and ST3 was the dominant ST type.The main virulence genes of clinical isolates were tlh+,tdh+,and trh-(79.86%),whereas the virulence genes in food isolates were all tlh+,tdh-,and trh-.Strains of the same serotype clustered together in the SNP phylogenetic tree.The environmental isolates showed no obvious dominant serotype or ST type.In Suzhou,VP has a high proportion of multi-drug resistance,the clinical isolates have prevalent serotypes and ST types,and most isolates carried virulence genes;there-fore,monitoring should be strengthened.

Objective To investigate the effects of long non-coding RNA FGD5-AS1 on the proliferation,migration,and invasion of pituitary adenoma(PA)cells,and to analyze its potential mechanism of action.Methods Human PA cell lines HPAs,RC-4BC,HP75,and human astrocyte cell line NHA were cultured in vitro.The expression levels of FGD5-AS1 and miR-15a in the above cell lines were detected by RT-PCR.HP75 cells in the logarithmic growth phase were randomly divided into the silencing group and the negative control group.The silencing group was transfected with shRNA-FGD5-AS1,while the negative control group was transfected with shRNA-NC.The expression levels of FGD5-AS1 and miR-15a in the two groups of cells were detected by RT-PCR.The proliferation,migration and invasion abilities of the two groups of cells were determined by CCK-8 assay,wound healing assay,and Transwell assay.The expression of proteins related to the Wnt/β-catenin signaling pathway in the two groups of cells was detected by Western blot.The targeting relationship between FGD5-AS1 and miR-15a was verified by dual-luciferase reporter gene assay.Results Compared with the NHA cell,the expression level of FGD5-AS1 was significantly increased in the HPAs,RC-4BC,and HP75 cells((P<0.05),whereas the expression level of miR-15a was significantly decreased(P<0.05).Compared with the negative control group,the expression level of FGD5-AS1 was decreased(P<0.05),the expression level of miR-15a was increased(P<0.05),the OD value was decreased(P<0.05),the migration and invasion abilities of cells were reduced(P<0.05),and the expression of Wnt3a and β-catenin proteins was decreased in the silencing group of HP75 cells(P<0.05).FGD5-AS1 could specifically bind to miR-15a,leading to a decrease in cell luciferase activity(P<0.05).Conclusion FGD5-AS1 is overexpressed in PA cells,and silencing FGD5-AS1 can inhibit the proliferation,migration,and invasion of PA cells,and the mechanism is related to its targeted regulation of miR-15a.