Objective To investigate the beneficial effect of Kai-Xin-San combined with fluoxetine in improving depression-like behaviors on chronic unpredictable mild stress(CUMS)induced depression model mice.Methods The present study aimed to assess the potential of Kai-Xin-San in combination with fluoxetine to ameliorate depression-like behaviors in a CUMS induced mouse depression model.Behavioral tests,such as the sucrose preference test were employed to evaluate the efficacy of the treatment.Additionally,the levels of suppressed stress factors were measured using the ELISA method.The morphology of hippocampal tissue was evaluated using the HE staining method,Nissl Staining and TUNEL staining methods.Furthermore,western blotting analysis was utilized to determine the expression levels of proteins such as Caspase-3,and Caspase-9.Results The co-administration of Kai-Xin-San and fluoxetine resulted in a significant increase in sucrose preference rate in model mice.This effect was comparable to that of fluoxetine alone at the standard clinical dose.Furthermore,the combination treatment up-regulated the levels of suppressed stress factors,reduced the apoptosis of hippocampus induced by depression and regulated the apoptosis signaling pathway in hippocampus.Conclusion The combination of Kai-Xin-San and fluoxetine has been shown to be an effective treatment for depression-like behavior in animal models,resulting in a reduction in the required clinical dosage of fluoxetine.This effect may be attributed to the up-regulation of neurotransmitter expression,inhibition of stress axis activation,and central nervous inflammation.

Objective To analyze TCM master Yan Zhenghua's medication rules of ascending,descending,floating and sinking properties for the treatment of respiratory diseases,inherit his valuable academic experience.Methods Using four books edited by Professor Yan Zhenghua's disciples as the main source,Professor Yan Zhenghua's prescriptions for clinical treatment of respiratory diseases were systematically collected and analyzed.Statistical analysis was conducted on the patients'gender and age,differentiation of diseases and syndrome types of the prescriptions,as well as the properties of ascending,descending,floating and sinking,dosage,and commonly used pairs of Chinese materia medica.Results Totally 208 prescriptions were included in this study,involving 178 kinds of Chinese materia medica and 64 kinds of monarch drug,most of them were descending and sinking drug,and the whole prescription was mainly descending and sinking.On average,each prescription used 13.2 kinds of Chinese materia medica,and most dosage points were within the range of conventional dosage.Among later adding medicines,Houttuyniae Herba had the highest frequency of use.The medicinal pairs of Asteris Radix et Rhizoma-Cynanchi Stauntonii Rhizoma et Radix,Cynanchi Stauntonii Rhizoma et Radix-Stemonae Radix and Asteris Radix et Rhizoma-Stemonae Radix were often used.Armeniacae Semen Amarum,Fritillariae Thunbergii Bulbus,and Asteris Radix et Rhizoma were commonly used in those descending and sinking prescriptions.Conclusion In the treatment of respiratory diseases,Professor Yan Zhenghua prefers to use descending and sinking drugs with ascending and floating drugs and dual trend drugs to regulate qi activity,and has the characteristics of Menghe medical school,which is"mild and flexible medication".

OBJECTIVE To construct the simulated traditional Chinese medicine pharmacy based on virtual simulation technology， and assist in the development of the new mode of traditional Chinese medicine dispensing education training. METHODS The field research and questionnaire surveys were conducted to identify the needs of Chinese medicine students and practitioners for the content and presentation of knowledge on the construction of simulated traditional Chinese medicine pharmacy. Taking the laws and regulations on the construction of traditional Chinese medicine pharmacy and the related teaching materials and literature on traditional Chinese medicine preparation as the knowledge source， the virtual simulation technology was applied to build a simulated traditional Chinese medicine pharmacy so as to achieve the functions of browsing the traditional Chinese medicine pharmacy， learning the knowledge of traditional Chinese medicine preparation and practical skills training. A multi-site simulated traditional Chinese medicine pharmacy evaluation scale study was conducted based on platform operational testing. RESULTS A simulated traditional Chinese medicine pharmacy was constructed， consisting of four core modules： video teaching， animation video， simulated pharmacy， and simulated experience. The overall score of evaluation scale was 93.31， with all entries scoring above 80； the ones with evaluation scales above 90 accounted for 92.31% （60/65）. CONCLUSIONS Simulated traditional Chinese medicine pharmacy based on virtual simulation technology meets the learning needs of users and enhances the teaching effect of traditional Chinese medicine dispensing technology training.

bjective　To analyze the drug resistance screening status and drug resistance influencing factors of high-risk groups of drug-resistant pulmonary tuberculosis in Qingdao, and to understand the inclusion of rifampicin patients in treatment, so as to provide a reference for the prevention and treatment of drug-resistant pulmonary tuberculosis. Methods　The medical records of 726 cases of drug-resistant pulmonary tuberculosis among high-risk populations registered in Qingdao from 2018 to 2022 were obtained from the National Health Insurance Information System of the China Center for Disease Control and Prevention. The drug resistance to five anti-tuberculosis drugs, namely isoniazid (INH), rifampicin (RFP), ethambutol (EMB), levofloxacin (Lfx), and amikacin (Am), in the high-risk populations of drug-resistant pulmonary tuberculosis was analyzed. Univariate and multivariate logistic regression were used toidentify factors influencing rifampicin resistance, and the detection and inclusion of treatment for rifampicin-resistant patients were evaluated. Results　Of the 726 subjects, 278 were drug-resistant, with a total drug resistance rate of 38.29%. The drug resistance for the five anti-tuberculosis drugs in descending order was: INH 25.90%(188/726), RFP 22.87%(166/726), Lfx 14.19%(103/726), EMB 11.29%(82/726), Am 2.48%(18/726). Analysis of the drug resistance spectrum showed that among those resistant to one drug, RFP was most common, accounting for 13.67% (38/278); among those resistant to two drugs, INH+RFP was predominant, accounting for 15.83% (44/278); among those resistant to three drugs, INH+RFP+Lfx was most frequent, at 7.19% (22/278); and among those resistant to four drugs, INH+RFP+EMB+Lfx was highest, at 6.12% (17/278). Multivariate logistic regression analysis of rifampicin resistance showed that compared with patients under 25 years of age, the risk of developing rifampicin resistance was lower in the groups aged 45 to under 65 and those aged 65 and above (OR=0.356, 95%CI: 0.181-0.700; OR=0.352, 95%CI: 0.170-0.729). Compared with migrant patients in other provinces, local patients from within the same county or district had a lower risk of developing rifampicin resistance (OR=0.599, 95%CI:0.383-0.962). Compared with patients who were smear-positive at the end of the second month of initial treatment, the risk of developing rifampicin resistance was higher in patients with relapse/return, failure of retreatment/chronic, and other categories of patients (OR=9.380, 95%CI:3.717-23.671;OR=25.749, 95%CI:8.037-82.490; OR=36.651, 95%CI:8.438-159.201). Conclusions　The situation of drug-resistant pulmonary tuberculosis in Qingdao cannot be ignored. Individuals under 25 years old, migrants from other provinces, and patients with relapse/return, failure of retreatment/chronic, and other categories are significant risk factors for developing rifampicin resistance in the high-risk groups of drug-resistant pulmonary tuberculosis.

Background and Aims:Sonodynamic therapy(SDT)is an emerging tumor treatment method that primarily utilizes low-intensity ultrasound(US)to activate sonosensitizers,leading to the production of cytotoxic reactive oxygen species(ROS)that kill cells.This study was conducted with an attempt to develop a novel nanoparticle(NPs)formulation containing a sonosensitizer and the small interfering RNA(siRRS1)of tumor-related gene RRS1 to observe its anticancer effects on colon cancer,to provide new strategies for colon cancer treatment. Methods:RRS1 RNA-Seq data were downloaded from the TCGA and GEO databases,and clinical pathological data were collected from 80 patients with colon cancer at Hunan Provincial People's Hospital.The expression of RRS1 in colon cancer and its relationship with prognosis were analyzed.The proliferation and apoptosis of colon cancer cells transfected with siRRS1 were observed.The sonosensitizer tetra(4-carboxyphenyl)porphyrin(TCPP),gene carrier DSPE-PEI,and siRRS1 were assembled into TCPP@DSPE-PEI-siRRS1 NPs(T@D-siRRS1 NPs).After structural characterization and examination of cellular uptake and ROS generation capabilities in vitro,the anticancer effects of T@D-siRRS1 NPs on colon cancer were assessed in cell experiments and tumor-bearing mouse models. Results:Both database analysis and clinical specimen testing indicated that RRS1 expression in colon cancer tissues was higher than that in adjacent normal tissues,and high expression was associated with poor prognosis(HR=1.88,95％CI=1.27-2.79,P=0.002).Univariate and multivariate analyses showed that RRS 1 mRNA expression was an independent risk factor for overall survival in colon cancer patients(HR=1.354,95％CI=1.447-2.215,P=0.031).Knockdown of RRS1 significantly reduced the proliferation capacity of colon cancer cells and increased apoptosis(both P＜0.05).Characterization results showed that the particles were uniform and stable;T@D-siRRS1 NPs entered cells through endocytosis,where TCPP could generate singlet oxygen(1O2)under ultrasound irradiation.Subsequent in vitro and in vivo experimental results demonstrated that transfection with NPs carrying siRRS1 or TCPP(T@D-control siRNA,T@D-siRRS1)combined with US resulted in varying degrees of growth inhibition in colon cancer cells,with the T@D-siRRS1 NPs+US treatment showing the strongest effect(all P＜0.05).Moreover,no significant damage was observed in the vital organs of mice treated with T@D-siRRS1 NPs+US. Conclusion:T@D-siRRS1 NPs plus US integrate SDT and gene therapy,producing an effective synergistic cytotoxic effect on colon cancer cells.Additionally,T@D-siRRS1 NPs demonstrate good safety and biocompatibility,suggesting potential for clinical application.

TCM dispensing is the most basic clinical pharmaceutical work of TCM.In recent years,based on the 9 key technologies of TCM dispensing,the TCM dispensing industry has ushered in great development,and innovative TCM dispensing information system and intelligent dispensing equipment have appeared.This article sorted out the current situation of TCM dispensing industry and looked forward to its future development route.The results showed that the introduction of new technology and new equipment in the key technical links of procurement acceptance,dispensing review,TCM decocting,medication guidance and so on have improved the quality of dispensing service and ensured the quality and safety of medication.In the development of modern TCM dispensing industry,it is necessary to improve the quality control standard system,service standard system and core equipment standard system in the standardization of dispensing technology;in terms of talent cultivation in the field of dispensing,it is necessary to focus on restructuring and building new educational models to cultivate new medical talents that intersect medical and engineering fields;in terms of informatization and intelligence,it is necessary to develop intelligent equipment that is more in line with the characteristics of TCM,and further promote and improve the"shared TCM pharmacy"model.Through improving the content of TCM clinical pharmaceutical care,developing new technology and equipment of TCM dispensing,and improving the level of dispensing service and education,it is expected to gradually realize the standardization,informatization and intelligent development of modern TCM dispensing industry.

Objective:To investigate the effect of preoperative use of diuretics on cardiac surgery-associated acute kidney injury(CSA-AKI)in elderly patients.Methods:In this single-center retrospective study, 1 638 patients aged ≥60 years and undergone cardiac surgery(including coronary artery bypass grafting, valve replacement and valvuloplasty)in the Department of Cardiovascular Surgery, Linyi People's Hospital between January 2015 and December 2022 were recruited.The last preoperative serum creatinine(SCr)level was taken as the baseline value, and AKI was diagnosed according to the Kidney Disease Improving Global Outcomes(KDIGO)criteria.Patients were divided into an AKI group and a non-AKI group according to whether AKI occurred after surgery.The clinical characteristics of the two groups were compared, and the effect of preoperative use of diuretics on CSA-AKI was evaluated by multivariate Logistic regression analysis.Results:Of 1638 patients enrolled in the study, 284 patients(17.3%)developed CSA-AKI.Compared with the non-AKI group, there were higher proportions of patients in the AKI group receiving furosemide(62.7% or 178/284 vs.46.2% or 626/1 354, χ2=25.397, P<0.001), spironolactone(70.1% or 199/284 vs.49.9% or 676/1 354, χ2=38.284, P<0.001), and hydrochlorothiazide(8.1% or 23/284 vs.3.5% or 47/1354, χ2=12.288, P<0.001). The number of diuretics in the AKI group was higher than in the non-AKI group[2(0, 2) vs.1(0, 2), Z=-6.381, P<0.001], and the proportion of patients using ≥2 diuretics was higher in the AKI group than in the non-AKI group(70.1% or 199/284 vs.49.0% or 664/1354, χ2=41.652, P<0.001). Multivariate Logistic regression analysis showed that, after adjusting for hypertension, diabetes mellitus, hypoalbuminemia, NYHA functional class Ⅲ/Ⅳ, cardiopulmonary bypass during surgery, operative duration≥6 h, postoperative blood transfusion>600 ml, postoperative use of >3 vasoactive drugs and other variables, preoperative use of ≥2 diuretics remained an independent risk factor for CSA-AKI in elderly patients( OR=1.580, 95% CI: 1.042-2.396, P=0.031). Conclusions:AKI is a common complication after cardiac surgery in elderly patients.Preoperative use of ≥2 diuretics used may be an independent risk factor for CSA-AKI.

In order to make the shared traditional Chinese medicine （TCM） pharmacy develop more efficiently and normatively at the grass-roots level， using the “shared TCM pharmacy” as the retrieval word， this paper uses the literature research method to retrieve the reports， documents and policies from CNKI， the websites of people’s governments at all levels， the official websites of the State Administration of Traditional Chinese Medicine， people.com， China News Network， Xinhua News and other platforms before May 20， 2022， sort out the development mode and history of two “Internet plus” TCM pharmacies， namely “shared TCM pharmacies” and “smart TCM pharmacies”， and compare them with each other. Combined with the actual work of community hospitals and community service centers （stations）， the necessity and advantages （such as reducing the costs of the intermediate links of drug circulation and standardizing the grass-roots drug use process） of the development of “shared TCM pharmacy” are obtained from the perspective of primary medical care. Combined with the current situation of the promotion and application of shared TCM pharmacy in county medical communities， it is concluded that the shared TCM pharmacy should be further constructed from four aspects： improving the work process of drug centralized procurement under the background of normalization， improving the compatibility and synchronization of the whole process dispensing information system module， unifying pharmaceutical services and personnel training， defining the authority of data query and clarifying the boundaries of patient privacy to further build a shared TCM pharmacy. Finally， it integrates information technology， summarizes the definition of shared TCM pharmacy and its future construction direction， and provides reference for the next development of shared TCM pharmacy at the grass-roots level.

Objective:To analyze the risk factors of acute renal injury (AKI) after coronary artery bypass grafting (CABG) in the elderly patients.Methods:A total of 423 patients aged over 60 years who underwent CABG in Linyi People′s Hospital from May 2014 to May 2010 were retrospectively analyzed. Patients were divided into AKI group and control group according to whether AKI occurred. The risk factors of AKI were analyzed by multivariate logistic regression.Results:Among the 423 patients, 62 cases(14.7%)developed postoperative acute kidney injury. Compared with the patients without AKI ( n=361), the proportions of patients with hypertension, heart function (NYHA) ≥ Ⅲ, atrial fibrillation and cardiopulmonary bypass were higher in AKI group, the proportion of patients using statins before operation was lower [71.0%(44/62) vs. 50.7%(183/361),χ 2 =8.75, P<0.01;38.77%(24/62) vs. 7.5%(27/361),χ 2 =48.67, P<0.01;16.1%(10/62) vs. 4.4%(16/361),χ 2 =12.55, P<0.01;51.6%(32/62) vs. 21.3%(77/361),χ 2 =25.37, P<0.01;59.7%(37/62) vs. 85.6%(309/361),χ 2=23.87, P<0.01]. Patients in AKI group had higher level of blood uric acid, urea nitrogen and creatinine [353.8(275.5, 462.5)μmol/L vs. 314.5(262.9, 383.6)μmol/L, Z=2.75, P=0.01;5.5(4.3, 8.2)mmol/L vs. 5.1(4.3, 6.4)mmol/L, Z=2.44, P＝0.02; 74.9(58.5, 92.7)μmol/L vs. 67.0(57.1, 76.3)μmol/L, Z=2.90, P=0.01];and longer operation time, more blood loss and blood vessel bridge than those in control group [(403.2±124.1) vs. (350.6±110.2), t =3.41, P<0.01;(4.0±0.9) vs. (3.7±0.8), t=2.83, P=0.01;(3.8±0.7) vs. (3.5±0.8), t=3.58, P<0.01]. The multivariate logistic regression analysis showed that preoperative cardiac function (NYHA)≥Ⅲ( OR=8.528,95% CI:3.734-19.477, P<0.01),hypertension( OR=6.455,95% CI:2.605-15.997, P<0.01),extracorporeal circulation( OR＝3.046,95% CI:1.190-7.795, P=0.02),diabetes mellitus( OR=2.294,95% CI:1.047-5.026, P=0.04),elevated serum uric acid level( OR=1.004,95% CI:1.000-1.008, P=0.03)were the independent risk factors for AKI. Statins is a protective factor for postoperative AKI( OR=0.366,95% CI:0.154-0.873, P=0.02). Conclusions:AKI is a common complication after CABG in elderly patients. Cardiac function(NYHA) ≥ Ⅲ,hypertension,extracorporeal circulation,diabetes mellitus,elevated serum uric acid level are risk factors and administration of stating is protective factor for the incidence of acute kidney injury in elderly patients after coronary artery bypass grafting.

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated proteins (Cas) system is a hotspot of gene editing and gene expression research, in which CRISPR/Cas13 system provides a new direction for RNA interference and editing. In this study, we designed and synthesized the corresponding gRNAs of CRISPR/Cas13a and CRISPR/Cas13b systems in non-homologous end joining (NHEJ) pathway, such as Ku70 and Lig4, and then detected the expression of ku70 and lig4 in HEK293T cells. The CRISPR/Cas13a system could efficiently knockdown the mRNA expression of ku70 and lig4 more than 50%, and CRISPR/Cas13b system also suppressed ku70 and lig4 about 92% and 76%, respectively. Also, CRISPR/Cas13a, b systems could down-regulate Ku70 and Lig4 proteins level to 68% and 53%, respectively. The study demonstrates that the CRISPR/Cas13 system could effectively knockdown the expression of RNA and protein in HEK293T cells, providing a new strategy for gene function and regulation research.
CRISPR-Cas Systems ; DNA Ligase ATP ; genetics ; Gene Expression Regulation ; genetics ; Gene Knockdown Techniques ; HEK293 Cells ; Humans ; Ku Autoantigen ; genetics