OBJECTIVE To investigate the clinical efficacy of integrating pharmacists into family health teams （FHTs） for long-term medication therapeutical management （MTM） in stroke patients， and empirically evaluate the service model. METHODS A pharmacist team， jointly established by clinical and community pharmacists from the Affiliated Suzhou Hospital of Nanjing Medical University （hereinafter referred to as “our hospital”）， developed a pharmacist-supported MTM model integrated into FHTs. Using a prospective randomized controlled design， 170 stroke patients discharged from our hospital （July 2022-December 2023） and enrolled in FHTs at Suzhou Runda Community Hospital were randomly divided into trial group （88 cases） and control group （82 cases） according to random number table. The control group received routine FHTs care （without pharmacist involvement in the team collaboration）， while the trial group xhz8405@126.com received 12-month MTM services supported by pharmacists via an information platform. These services specifically included innovative interventions such as personalized medication regimen optimization based on the MTM framework， dynamic medication adherence management， medication safety monitoring， a home medication assessment system， and distinctive service offerings. Outcomes of the 2 grousp were compared before and after intervention， involving medication adherence （adherence rate， adherence score）， compliance rates for stroke recurrence risk factors [blood pressure， low-density lipoprotein cholesterol （LDL-C）]， and incidence of adverse drug reactions （ADR）. RESULTS After 12 months， the trial group exhibited significantly higher medication adherence rates， improved adherence scores， higher compliance rates for blood pressure and LDL-C targets compared to the control group （P＜0.05）. The incidence of ADR in the trial group （4.55%） was significantly lower than that in the control group （8.11%）， though the difference was not statistically significant （P＞ 0.05）. CONCLUSIONS Pharmacist involvement in FHTs to deliver MTM services significantly enhances medication adherence and optimizes risk factor for stroke recurrence， offering practical evidence for advancing pharmaceutical care in chronic disease management under the family doctor system.

OBJECTIVE: Blood culture remains the gold standard for diagnosing bloodstream infections. Clinical laboratories must ensure the quality of blood culture processes from receipt to obtaining definitive results. We examined laboratory analytical indicators associated with positive blood culture results. METHODS: Blood cultures collected from Peking Union Medical College Hospital between January 1, 2020, and December 31, 2022, were retrospectively analyzed. The mode of transportation (piping logistics delivery vs. staff), source of blood cultures (outpatient/emergency department vs. inpatient department), rotation of personnel, and time of reception (8:00-19:59 vs. 20:00-07:59) were compared between blood culture-positive and -negative results. RESULTS: Between 2020 and 2022, the total positive rate of blood culture was 8.07%. The positive rate of blood cultures in the outpatient/emergency department was significantly higher than that in the inpatient department (12.46% vs. 5.83%; P < 0.0001). The time-to-detection of blood cultures was significantly affected by the delivery mode and personnel rotation. The blood culture positive rate of the total pre-analytical time within 1 h was significantly higher than that within 1-2 h or > 2 h ( P < 0.0170). CONCLUSION Laboratory analytical indicators such as patient source, transportation mode, and personnel rotation significantly impacted the positive detection rate or time of blood culture.
Blood Culture/statistics & numerical data* ; Humans ; Retrospective Studies ; Emergency Service, Hospital/statistics & numerical data*

OBJECTIVE: To investigate the effects of mTOR inhibitors everolimus (EVE) and gemcitabine (GEM) on the proliferation, apoptosis and cell cycle of diffuse large B-cell lymphoma (DLBCL) cell line U2932, and further explore the molecular mechanisms, so as to provide new ideas and experimental basis for the clinical treatment of DLBCL. METHODS: The effect of EVE and GEM on the proliferation of U2932 cells was detected by CCK-8 assay, the IC₅₀ of the two drugs was calculated, and the combination index (CI=) of the two drugs was calculated by CompuSyn software. The effect of EVE and GEM on apoptosis of U2932 cells was detected by flow cytometry with AnnexinV-FITC/PI staining. Flow cytometry with propidium iodide (PI) staining was used to detect the effect of EVE and GEM on the cell cycle of U2932 cells. Western blot assay was used to detect the effects of EVE and GEM on the channel proteins p-mTOR and p-4EBP1, the anti-apoptotic proteins MCL-1 and Survivin, and the cell cycle protein Cyclin D1. RESULTS: Both EVE and GEM could significantly inhitbit the proliferation of U2932 cells in a time- and dose-dependent manner (r=0.465, 0.848; 0.555, 0.796). According to the calculation of CompuSyn software, EVE combined with GEM inhibited the proliferation of U2932 cells at 24, 48 and 72 h with CI=<1, which had a synergistic effect. After treated U2932 cells with 10 nmol/L EVE, 250 nmol/L GEM alone and in combination for 48 h, both EVE and GEM induced apoptosis, and the difference was statistically significant compared with the control group (P<0.05). The apoptosis rate was significantly enhanced after EVE in combination with GEM compared with single-agent (P<0.05). Both EVE and GEM alone and in combination significantly increased the proportion of cells in G₁ phase compared with the control group (P<0.05). The proportion of cells in G₁ phase was significantly increased when the two drugs were combined (P<0.05). The expression of p-mTOR and effector protein p-4EBP1 was significantly downregulated in the EVE combined with GEM group, the expression of anti-apoptotic proteins MCL-1, Survivin and cell cycle protein cyclin D1 was downregulated too (P<0.05). CONCLUSION EVE combined with GEM can synergistically inhibit the proliferation of U2932 cells, and the mechanism may be that they can synergistically induce apoptosis by downregulating the expression of MCL-1 and Survivin proteins and block the cell cycle progression by downregulating the expression of Cyclin D1.
Humans ; Gemcitabine ; Everolimus/pharmacology* ; Survivin/pharmacology* ; Cyclin D1/pharmacology* ; Myeloid Cell Leukemia Sequence 1 Protein ; Cell Line, Tumor ; Cell Proliferation ; TOR Serine-Threonine Kinases ; Apoptosis ; Apoptosis Regulatory Proteins ; Cell Cycle Proteins ; Lymphoma, Large B-Cell, Diffuse

OBJECTIVE: To investigate the distribution and antimicrobial susceptibility of causative microorganisms recovered from patients with intra-abdominal infections (IAIs). METHODS: A total of 2,926 bacterial and fungal strains were identified in samples collected from 1,679 patients with IAIs at the Peking Union Medical College Hospital between 2011 and 2021. Pathogenic bacteria and fungi were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Antimicrobial susceptibility testing (AST) was performed using the VITEK 2 compact system and the Kirby-Bauer method. AST results were interpreted based on the M100-Ed31 clinical breakpoints of the Clinical and Laboratory Standards Institute. RESULTS: Of the 2,926 strains identified, 49.2%, 40.8%, and 9.5% were gram-negative bacteria, gram-positive bacteria, and fungi, respectively. Escherichia coli was the most prevalent pathogen in intensive care unit (ICU) and non-ICU patients; however, a significant decrease was observed in the isolation of E. coli between 2011 and 2021. Specifically, significant decreases were observed between 2011 and 2021 in the levels of extended-spectrum β-lactamase (ESBL)-producing E. coli (from 76.9% to 14.3%) and Klebsiella pneumoniae (from 45.8% to 4.8%). Polymicrobial infections, particularly those involving co-infection with gram-positive and gram-negative bacteria, were commonly observed in IAI patients. Moreover, Candida albicans was more commonly isolated from hospital-associated IAI samples, while Staphylococcus epidermidis had a higher ratio in community-associated IAIs. Additionally, AST results revealed that most antimicrobial agents performed better in non-ESBL-producers than in ESBL-producers, while the overall resistance rates (56.9%-76.8%) of Acinetobacter baumanmii were higher against all antimicrobial agents than those of other common gram-negative bacteria. Indeed, Enterococcus faecium, Enterococcus faecalis, S. epidermidis, and S. aureus were consistently found to be susceptible to vancomycin, teicoplanin, and linezolid. Similarly, C. albicans exhibited high susceptibility to all the tested antifungal drugs. CONCLUSION The distribution and antimicrobial susceptibility of the causative microorganisms from patients with IAIs were altered between 2011 and 2021. This finding is valuable for the implementation of evidence-based antimicrobial therapy and provides guidance for the control of hospital infections.
Humans ; Anti-Bacterial Agents ; Escherichia coli ; Gram-Negative Bacteria ; Gram-Positive Bacteria ; Retrospective Studies ; Staphylococcus aureus ; Intraabdominal Infections/epidemiology* ; Candida albicans ; Coinfection

OBJECTIVE: To investigate the correlation between single-nucleotide polymorphism (SNP) of ARID5B gene and resistance to methotrexate (MTX) in children with acute lymphoblastic leukemia (ALL). METHODS: A total of 144 children with ALL who were treated in General Hospital of Ningxia Medical University from January 2015 to November 2021 were enrolled and divided into MTX resistant group and non-MTX resistant group, with 72 cases in each group. Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) technology was used to measure the SNP of ARID5B gene in all children and analyze its correlation with MTX resistant. RESULTS: There were no significant differences in the genotype and gene frequency of rs7923074, rs10821936, rs6479778, and rs2893881 between MTX resistant group and non-MTX resistant group (P>0.05). The frequency of C/C genotype in the MTX resistant group was significantly higher than that in the non-MTX resistant group, while the frequency of T/T genotype was opposite (P<0.05). The frequency of C allele in the MTX resistant group was significantly higher than that in the non-MTX resistant group, while the frequency of T allele was opposite (P<0.05). Multivariate logistic regression analysis showed that ARID5B gene rs4948488 TT genotype and T allele frequency were risk factors for MTX resistant in ALL children (P<0.05). CONCLUSION The SNP of ARID5B gene is associated with MTX resistant in ALL children.
Child ; Humans ; DNA-Binding Proteins/genetics* ; Gene Frequency ; Genotype ; Methotrexate ; Polymorphism, Single Nucleotide ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Transcription Factors/genetics* ; Drug Resistance, Neoplasm

Objective: To evaluate the efficacy and safety of fecal microbiota transplantation (FMT) in the treatment of autism spectrum disorder (ASD). Methods: A longitudinal study was conducted. Clinical data from ASD patients with gastrointestinal symptoms and who underwent FMT in the Tenth People's Hospital affiliated to Tongji University or Jinling Hospital between May 2012 to May 2021 were retrospectively collected. Scores derived from the autism behavior checklist (ABC), the childhood autism rating scale (CARS), the Bristol stool form scale (BSFS), and the gastrointestinal symptom rating scale (GSRS) were analyzed at baseline and at the 1st, 3rd, 6th, 12th, 24th, 36th, 48th and 60th month after FMT. Records of any adverse reactions were collected. Generalized estimating equations were used for analysis of data on time points before and after FMT. Results: A total of 328 patients met the inclusion criteria for this study. Their mean age was 6.1±3.4 years old. The cohort included 271 boys and 57 girls. The percentage of patients remaining in the study for post-treatment follow-up at the 1st, 3rd, 12th, 24th, 36th, 48th and 60th month were as follows: 303 (92.4%), 284 (86.7%), 213 (64.9%), 190 (57.9%), 143 (43.6%), 79 (24.1%), 46 (14.0%), 31 (9.5%). After FMT, the average ABC score was significantly improved in the first 36 months and remained improved at the 48th month. However, the average score was not significantly different from baseline by the 60th month (1st-36th month, P<0.001; 48th month, P=0.008; 60th month, P=0.108). The average CARS score improved significantly during the first 48 months and remained improved at the 60th month (1st-48th month, P<0.001; 60th month, P=0.010). The average BSFS score was also significantly improved in the first 36 months (with an accompanying stool morphology that resembled type 4). This improvement was maintained at the 48th month. However, the average score was similar to baseline at the 60th month (1st-36th month, P<0.001; 48th month, P=0.008; 60th month, P=0.109). The average GSRS score was significantly improved during the first 24 months, but not afterwards (1st-24th month, P<0.001; 36th month, P=0.209; 48th month, P=0.996; 60th month, P=0.668). The adverse events recorded during treatment included abdominal distension in 21 cases (6.4%), nausea in 14 cases (4.3%), vomiting in 9 cases (2.7%), abdominal pain in 15 cases (4.6%), diarrhea in 18 cases (5.5%), fever in 13 cases (4.0%), and excitement in 24 cases (7.3%). All adverse reactions were mild to moderate and improved immediately after suspension of FMT or on treatment of symptoms. No serious adverse reactions occurred. Conclusion: FMT has satisfactory long-term efficacy and safety for the treatment of ASD with gastrointestinal symptoms.
Autism Spectrum Disorder/therapy* ; Child ; Child, Preschool ; Fecal Microbiota Transplantation/adverse effects* ; Feces ; Female ; Gastrointestinal Diseases ; Humans ; Longitudinal Studies ; Male ; Retrospective Studies

Objective: To explore and establish the preparation system of human intestinal fluid transplantation (HIFT) and HIFT capsule, and to preliminarily apply it to clinic. Methods: Strict standards for donor screening and management were established. The nasojejunal tube was catheterized into the distal jejunum, and then it was connected with an improved disposable sterile negative pressure collection device for the collection of human intestinal fluid. After that, it was prepared into capsules by filtering, adding 10% glycerin protectant and freeze-drying method. The amount of living bacteria was used as the standard of therapeutic dose. The living bacteria amount in fluid is ≥ 5.0×10⁸ /mL and the living bacteria proportion is ≥ 83%; the living bacteria amount in powder is ≥ 2.0×10⁶ /g and the living bacteria proportion is ≥ 81%; The observational indicators included: (1) the basic information of the donor, the amount of living bacteria in the HIF and powder. (2) Preliminary analysis of the treatment for ASD, which combined HIFT capsule with standard FMT capsule, from February to December 2021 (Clinical trial Registration Number: ChiCTR2100043929). Evaluation criteria: Trypan blue staining method was used to detect the living bacteria amount in fluid and powder. The Autism Behavior Checklist (ABC) and Childhood Autism Rating Scale (CARS) were used to evaluate the efficacy. Results: Compared with the parent donor, the standard donor was younger [(25.4±0.9) y vs. (30.7±3.2) y, t=-19.097, P=0.001] and had a lower body mass index [(19.7±0.5) kg/m² vs. (20.8±1.3) kg/m², t=-8.726, P=0.001], more in the living bacteria amount in powder [(7.47±1.52)×10⁶/g vs. (5.03±1.38)×10⁶/g, t=11.331, P=0.031], Chao index (205.4±6.8 vs. 194.2±7.2, t=10.415, P=0.001), and Shannon index (3.25±0.14 vs 2.72±0.27, t=19.465, P=0.001). The differences were statistically significant (all P<0.05). However, there were no significant differences in gender, drainage volume and total number of bacterial liquid colonies between the two groups (all P>0.05). Both the standard donor and the parent donor met the donor screening criteria, and the preparation fluid and powder met the treatment criteria. Eight patients received the treatment of HIFT combined with fecal microbiota transplantation (FMT). Preliminary statistical results showed that HIFT combined with FMT improved ABC and CARS at the 1st, 2nd, 3rd and 4th months. The differences were statistically significant (all P<0.05). No severe adverse reaction occurred. Conclusion: Based on the previous research on FMT preparation system and the clinical technology in our center, this study developed a high standard HIFT preparation system, and explored the clinical study of HIFT combined with FMT, in order to provide an innovative therapy for the treatment of diseases.
Bacteria ; Child ; Fecal Microbiota Transplantation/methods* ; Glycerol ; Humans ; Powders ; Trypan Blue

Aim To study the nephrotoxicity effects of the main monomers in Zuojin Pills. Methods CCK-8 and high-content toxicity screening were used to preliminarily screen the main alkaloids in Zuojin Pills that may cause renal cell damage. Further, by confirmation of cell morphology, release rate of lactate dehydrogenase and cytochrome C, and expression of apoptosis-related proteins, the alkaloids causing cell damage were preliminarily identified, providing in vitro toxicological evidence for the compatibility of components of traditional Chinese medicine and compatibility attenuation. Results Preliminary screening using CCK-8 method and high-content technology showed that evodiamine (EVO) could significantly reduce cell number, increase cell membrane permeability, and reduce mitochondrial membrane potential. In addition, cell morphology, apoptosis and cytochrome C expression were consistent with the results of high-content screening. Western blot experiments indicate that EVO could induce apoptosis and cause renal cell damage. Conclusions EVO can obviously cause renal cell damage, and may induce apoptosis by affecting mitochondria, cytochrome C and cell membrane permeability.

Objective:To investigate the effects of Buyang Huanwutang on the expression of microtubule-associated protein-2（MAP-2）， neurofilament-M（NF-M）， and growth associated protein-43（GAP-43）in rat sciatic nerve after sciatic nerve transection and anastomosis. To explore the mechanism of Buyang Huanwutang promoting peripheral nerve regeneration. Method:SD rats were selected as the experimental subjects， and sciatic nerve transection model was selected as the experimental model. They were randomly divided into model group， sham operation group， Buyang Huanwutang group high， medium and low dose （29.6， 14.8， 7.4 g·kg^-1）group， and mecobalamin （0.156 mg·kg^-1）group， the model group and the sham operation group were given distilled water intragastric administration. After successful modeling， each group was treated with relevant drugs for 4 weeks. After 4 weeks， sciatic nerve function index（SFI）， degree of inclined plate test and hematoxylin-eosin（HE）of sciatic nerve in each group were tested. The expression levels of MAP-2， NF-M， and GAP-43 at the sciatic nerve anastomosis site were detected by immunohistochemistry and Western blot. Result:Compared with sham operation group， the expression levels of SFI， inclined plate test， MAP-2， NF-M and GAP-43 in model group were significantly increased （P<0.01）. Compared with model group， the expression levels of SFI， inclined plate test， MAP-2， NF-M and GAP-43 in Buyang Huanwutang high， medium and low-dose groups were significantly increased （P<0.05，P<0.01）. Conclusion:Buyang Huanwutang has a positive effect on nerve regeneration after sciatic nerve transection and anastomosis in rats.

Objective:Through phosphatidylinositol 3-kinase（PI3K）/protein kinase B （Akt）/mammalian rapamycin target protein （mTOR） signaling pathway， explore the effect of Zhigancao Tang on myocardial ischemia-reperfusion injury（MIRI）The role and mechanism of arrhythmia（ventricular tachycardia and ventricular fibrillation）. Method:The 72 SD rats were randomly divided into sham operation group，model group， Zhigancao Tang low，medium and high dose group（11.43，22.86，45.72 g·kg^-1），Wenxin granule group（2.43 g·kg^-1），continuous drug intervention for 10 days. Two hours after the last administration，the MIRI model of rat was prepared by ligating the left anterior descending coronary artery，and the changes of electrocardiogram were recorded. After successful modeling，blood and heart tissue were collected to detect the content of creatine creatine（CK），lactate dehydrogenase（LDH）and aspartate aminotransferase（AST）in the serum, the enzyme-linked immunoassay（ELISA） method was used to detect cardiac troponin（CtnI）content, immunohistochemical detection of myocardial PI3K，Akt，mTOR expression. Western blot was used to detect the myocardial autophagy-related protein microtubule-associated protein 1 light chain 3（LC-3），autophagy markers Beclin1 and PI3K/Akt/mTOR signaling pathway related protein expression and phosphorylated p-PI3K，p-Akt，p-mTOR levels. Result:In model group， 100% of ventricular tachycardia and 91.67% of ventricular fibrillation occurred. Compared with sham operation group， the serum levels of CK，LDH，AST，and CtnI in the model group were significantly increased（P<0.01），PI3K，Akt，mTOR AOD values in myocardial tissue were significantly increased （P<0.01），the relative expression of the ratio of LC3-Ⅱ/LC3-Ⅰ and Beclin1 was significantly increased（P<0.01），p-PI3K/PI3K，p-Akt/Akt，and p-mTOR/mTOR were significantly reduced （P<0.01）. Compared with model group， the incidence of ventricular tachycardia and ventricular fibrillation in the high-dose Zhigancao Tang group was significantly reduced （P<0.01），and the duration was the shortest compared with other administration groups（P<0.01）， CK，LDH，AST level and CtnI content were significantly reduced（P<0.01）， the expression of PI3K，Akt and mTOR of Zhigancao Tang group was significantly decreased with increasing dose（P<0.01）， the expression of LC-3 and Beclin1 was accompanied by Zhigancao Tang increase of each dose group of soup had different degrees of decrease （P<0.01），while the expression ratio of PI3K/Akt/mTOR-related protein was significantly increased （P<0.05，P<0.01）. Conclusion:Pretreatment of Zhigancao Tang can reduce the abusually elevated cardiac enzymes CK, LDH, AST and CtnI, inhibit excessive autophagy of cells, and up-regulate the expression of PI3K, Akt and mTOR, indicating that the anti-MIRI arrhythmia effect of Zhigancao Tang may be related to the PI3K/Akt/mTOR signaling pathway.