OBJECTIVE To establish a Chinese drug-related problem （DRP） classification system applicable to pharmacist-led pharmaceutical care in China， providing pharmacists with an effective and practical tool for pharmaceutical care. METHODS A multi-stage process was employed to construct the DRP classification system， including literature review and analysis， comparison of existing classification systems， refinement of classification items and framework development， two rounds of standard case validation， expert discussion， and system revision. The Fleiss′ kappa test was used to calculate the consistency coefficient κ， assessing the reliability of pharmacists participating in evaluating the classification system. An electronic questionnaire comprising six items was employed to evaluate the system’s applicability. RESULTS The constructed Chinese DRP classification system comprised six sections [problem（including potential problems）， DRP evaluation， cause （including possible causes of potential problems）， intervention， acceptance of intervention and DRP status]， with 24 primary codes and 96 secondary codes. In the first round of case validation， κ values exceeded 0.4 for all sections except “intervention” and “DRP status”. In the second round， κ values exceeded 0.4 for all sections. In the applicability evaluation of the classification system， positive ratings （“strongly agree” or “agree”） exceeded 85% for all items. Specifically， positive ratings for“the classification system can provide appropriate category selection”，“ the classification system is comprehensive”，“ the classification system is convenient to use” and “the classification system is highly satisfactory” exceeded 92%. CONCLUSIONS The Chinese DRP classification system developed demonstrates both high reliability and applicability， providing an effective and practical classification tool for pharmacists in China to conduct pharmaceutical care.

ObjectiveTo investigate the effects of zinc finger E-box binding homeobox 1 （ZEB1） on the proliferation， migration， and invasion of lung adenocarcinoma H322 cells， as well as its underlying molecular mechanisms. MethodsThe gene expression characteristics of the transcription factor ZEB1 in lung adenocarcinoma were analyzed using data from the GEO and TCGA public databases. RT-qPCR and Western blot were employed to measure mRNA and protein expression levels of ZEB1 in lung adenocarcinoma cell lines （H322， A549， 95-D） and normal human bronchial epithelial cells （BEAS-2B）. Lentiviral transduction was utilized to establish stable ZEB1-overexpressing （Oe-ZEB1） and vector control （Oe-NC） H322 cell lines. Cell proliferation was assessed using CCK-8， colony formation， and EdU assays， while apoptosis was evaluated by Hoechst33258/PI double staining. Wound healing and Transwell assays were performed to examine cell migration and invasion capabilities. Cell cycle distribution was determined by flow cytometry， and Western blot was used to analyze protein expression changes in relevant signaling pathways. ResultsThe findings from GEO and TCGA indicated that ZEB1 expression in lung adenocarcinoma varied with tumor malignancy grade. RT-qPCR and Western blot analyses revealed significantly higher ZEB1 expression in lung adenocarcinoma cell lines compared to BEAS-2B cells （P0.05）. Results from the CCK-8， colony formation， EdU， wound healing， and Transwell assays demonstrated that， compared with the un-transfected control （Control） group， Oe-ZEB1 H322 cells exhibited enhanced proliferation， migration， and invasion capabilities （P0.05）. Hoechst33258/PI double staining and flow cytometry analyses showed that， relative to the Control group， apoptosis was reduced in Oe-ZEB1 H322 cells （P0.05）. Additionally， a decreased proportion of cells in the G₁ phase and an increased proportion in the S phase were observed in Oe-ZEB1 cells， indicating accelerated cell cycle progression. Western blot analysis further revealed that， compared with the Control group， Oe-ZEB1 H322 cells exhibited upregulated expression of N-cadherin， mutant p53 （mutp53）， and Cyclin D1 （P0.05）， while expression levels of E-cadherin， murine double minute 2 （MDM2）， and p21 were downregulated （P0.05）. ConclusionOverexpression of ZEB1 promotes the proliferation， migration， and invasion of lung adenocarcinoma H322 cells and may facilitate cell cycle progression by modulating the MDM2/mutp53/p21 signaling pathway， thereby promoting the transition of cells from the G₀/G₁ phase to the S phase.

Objective : To investigate the protective effect of dimethyl fumarate(DMF) on maternal intrahepatic cholestasis(ICP) during pregnancy induced by di(2-ethylhexyl) phthalate(DEHP) exposure and its mechanism. Methods : Thirty-two 8-week-old female institute of cancer research(ICR) mice were randomly divided into 4 groups: Ctrl group, DEHP group, DMF group and DEHP+DMF group. DEHP and DEHP+DMF groups were treated with DEHP(200 mg/kg) by gavage every morning at 9:00 a.m. DMF and DEHP+DMF groups were treated with DMF(150 mg/kg) from day 13 to day 16 of gestation by gavage. After completion of gavage on day 16 of pregnancy, maternal blood, maternal liver, placenta, and amniotic fluid were collected from pregnant mice after a six-hour abrosia. The body weight of the mother rats and the body weight of the fetus rats were sorted and analyzed; the levels of total bile acid(TBA), alkaline phosphatase(ALP), aspartate aminotransferase/alanine aminotransferase(AST/ALT) in serum and TBA in liver, amniotic fluid and placenta were detected by biochemical analyzer; HE staining was used to observe the pathological changes of liver tissue; Quantitative reverse transcription PCR(RT-qPCR) was used to detect the expression levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-6, IL-1, IL-18 and NOD-like receptor thermal protein domain associated protein 3(NLRP3) in the liver; Western blot was used to detect the expression of the nuclear factor KappaB(NF-κB) and NLRP3. Results : Compared with the control group, the body weight of the DEHP-treated dams and pups decreased(P<0.05); the levels of TBA, ALP, AST/ALT in the serum of dams and the levels of TBA in the liver, amniotic fluid, and placenta of dams increased(P<0.05); the histopathological results showed that liver tissue was damaged, bile ducts were deformed, and there was inflammatory cell infiltration around them; the levels of inflammation-related factors TNF-α, IL-6, IL-1, IL-18 and NLRP3 transcription in maternal liver increased(P<0.05); the expression of NF-κB and NLRP3 protein in maternal liver significantly increased( P<0. 05). Compared with the DEHP group,the body weight of both dams and fetuses significantly increased in DEHP + DMF group( P<0. 05); the levels of TBA,ALP,AST/ALT in the serum of dams and amniotic fluid of fetuses decreased( P<0. 05); the degree of liver lesions was improved; the transcription levels of inflammation-related factors TNF-α,IL-6,IL-1,IL-18 and NLRP3 in maternal liver decreased( P<0. 05); the expression of NF-κB and NLRP3 protein in maternal liver significantly decreased( P<0. 05). Conclusion DMF can effectively protect the DEHP exposure to lead to female ICP,and its mechanism may be through inhibiting the NF-κB/NLRP3 pathway and reducing liver inflammation.

The medical mask,which is used as an important tool of preventing the spread of respiratory diseases,can effectively block the transmission of biological aerosols.The detection for the filtration efficiency of bacteria in medical mask is particular importance.The Andersen sampler,is one kind of device that samples microbial aerosols,is widely used in the inspection for the filtration efficiency for bacteria in medical masks.It mainly consists of six impactors with different pore sizes.It simulates the deposition process of the most of particles at different positions in respiratory system through the bacterial particles in biological aerosols impact respectively the surface of petri dishes with agar under different pore sizes.This paper explored the development background,structure and sampling principle,operation and counting procedures of the Andersen sampler,as well as its application and importance in the inspection for the filtration efficiency for bacteria in medical mask.

AIM To invesigate the quantitative transmitting rules of benchmark samples of Ganjiang Lingzhu Decoction.METHODS HPLC fingerprints were established,after which principal component analysis and partial least squares discriminant analysis were performed.The contents of 6-gingerol,liquiritin and glycyrrhizic acid were determined,after which their transfer rates and dry paste rate were calculated.RESULTS There were 22 common peaks in the fingerprints for 15 batches of benchmark samples with the similarities of more than 0.9.Various batches of benchmark samples were clustered into 3 categories,4 principal components demonstrated the accumulative variance contribution rate of 92.676％,and liquiritin made a great contribution to grouping.In various batches of medicinal materials-decoction pieces,decoction pieces-standard decoctions and standard decoctions-benchmark samples,the transfer rates of 6-gingerol were 84.72％-100.00％,14.29％-24.14％,88.60％-99.36％,those of liquiritin were 74.38％-100.00％,38.54％-64.20％,96.91％-100.30％,and those of glycyrrhizic acid were 68.28％-103.27％,28.48％-49.79％,92.93％-100.49％,the dry paste rate was 13.75％-16.41％.CONCLUSION The preparation process for benchmark samples of Ganjiang Lingzhu Decoction is stable,6-gingerol,liquiritin and glycyrrhizic acid can be taken as their quality markers.Fingerprint combined with content determination can provides a reference for the quality control of Ganjiang Lingzhu Decoction and their related preparations.

Objective:To investigate the relationship between serum apolipoprotein A1 (ApoA1), cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), proinflammatory protein S100A9 (S100A9) and prognosis in patients with myelodysplastic syndrome (MDS).Methods:122 MDS patients visited Qinhuangdao First Hospital from January 2020 to January 2021 were selected as the research objects. After three years of follow up, patients were divided into survival group and death group based on survival status. The differences in ApoA1, CTLA-4, and S100A9 between the death group and the survival group were compared. Measurement data with normal distribution was expressed as " xˉ±s", independent sample t-test was used on comparison between groups. Counting data was expressed as rate or composition ratio, χ2 test was used on comparison between groups. Univariate and multivariate Logistic regression analysis were used to analyze factors related to death. Results:There was no lost to follow up patients after three years of follow up. Among those 122 patients, 92 survived and 30 died. The ratio of bone marrow primitive cells>5%, IPSS-R score, serum CTLA-4, and S100A9 levels in the survival group were (2.89±2.15), (3.13±1.95) points, (5.12±1.59) μg/L, (1643.98±429.65)ng/L, respectively, lower than (5.67±3.76), (5.12±2.36) points, (28.67±6.98) μg/L, (2895.64±553.62) ng/L in the death group ( t=5.03, 4.60, 30.27, 12.87, respectively, all P<0.01). The relative high-risk ratio of IPSS-R stratification in the survival group was 63.04%,(58/92) which was lower than the 86.67%(26/30) in the death group ( χ2=5.89, P=0.015). The absolute values of hemoglobin, lymphocytes and neutrophils, and values of platelets and ApoA1 in the survival group were(86.74±12.69)g/L, (1.41±0.23)×10 9/L, (1.42±0.55)×10 9/L, (59.98±21.37)×10 9/L, (1.09±0.40) g/L respectively, which were higher than (65.58±10.89)g/L, (0.68±0.17)×10 9/L, (0.96±0.31)×10 9/L, (42.85±20.95)×10 9/L, (0.91±0.36)g/L in the death group ( t=8.20, 16.00, 4.35, 7.90, 2.19; respectively, P<0.001, <0.001, <0.001, <0.001, =0.030). Multivariate Logistic regression model analysis showed that, bone marrow blasts cells>5% ( OR=1.732, 95% CI: 1.188~2.523, P=0.004), relatively high IPSS-R stratification ( OR=1.815, 95% CI: 1.332~2.474, P<0.001), high IPSS-R score ( OR=1.785, 95% CI: 1.259~2.529, P=0.001), high CTLA-4 level ( OR=2.156, 95% CI: 1.482~3.134, P<0.001) and high S100A9 level ( OR=1.787, 95% CI: 1.218~2.625, P=0.003) were risk factors for poor prognosis in MDS patients, while high ApoA1 level ( OR=0.785, 95% CI: 0.658~0.937, P=0.007) was a protective factor ( P<0.05). Conclusion:The decrease in ApoA1 levels and the increase in CTLA-4 and S100A9 levels in MDS patients are associated with poor prognosis.

Objective:To investigate the efficacy and safety of bendamustine combined with anti-CD20 monoclonal antibody in the first-line treatment of older patients with indolent B-cell non-Hodgkin lymphoma (B-iNHL) .Methods:The clinical data of 159 patients with B-iNHL enrolled in 16 hospitals from Jiangsu Cooperative Lymphoma Group from December 1, 2019, to April 20, 2024, were analyzed for regimen efficacy and safety. Bendamustine plus rituximab (BR) and bendamustine plus obinutuzumab (BG) were administered to 139 (87.4% ) and 20 (12.6% ) patients, respectively.Results:Among the 159 patients, 101 (63.5% ) were male and 58 (36.5% ) were female, with a median age of 69 years (range: 60–84). Efficacy could be assessed in 138 (86.8% ) patients. The efficacy assessment demonstrated that the overall response rate was 92.0% with complete and partial remissions in 75 (54.3% ) and 52 (37.7% ) cases, respectively. With a median follow-up of 24 months (range: 4–64), the progression-free survival rate was (87.5 ± 3.0) % and the overall survival rate was (83.2 ± 3.3) %. Of the 27 patients who died, 6 (22.2% ) died due to disease progression. The mean applied dose of bendamustine per cycle was 73.0 (50.8–89.7) mg/m 2 per day, administered on days 1 and 2. Adverse events of grade 3 or higher were reported in 53 (33.3% ) patients, with infection (30 cases,18.9% ) and neutropenia (24 cases, 15.1% ) demonstrating the highest incidence. Conclusion:Bendamustine combined with anti-CD20 monoclonal antibody demonstrated good efficacy and is well-tolerated in the first-line treatment of elderly patients with B-iNHL.

This study was conducted retrospectively on a cohort of 68 patients with steroid 5 α-reductase 2 (SRD5A2) deficiency and 46,XY disorders of sex development (DSD). Whole-exon sequencing revealed 28 variants of SRD5A2 , and further analysis identified seven novel mutants. The preponderance of variants was observed in exon 1 and exon 4, specifically within the nicotinamide adenine dinucleotide phosphate (NADPH)-binding region. Among the entire cohort, 53 patients underwent initial surgery at Sichuan Provincial People's Hospital (Chengdu, China). The external genitalia scores (EGS) of these participants varied from 2.0 to 11.0, with a mean of 6.8 (standard deviation [s.d.]: 2.5). Thirty patients consented to hormone testing. Their average testosterone-to-dihydrotestosterone (T/DHT) ratio was 49.3 (s.d.: 23.4). Genetic testing identified four patients with EGS scores between 6 and 9 as having this syndrome; and their T/DHT ratios were below the diagnostic threshold. Furthermore, assessments conducted using the crystal structure of human SRD5A2 have provided insights into the potential pathogenic mechanisms of these novel variants. These mechanisms include interference with NADPH binding (c.356G>C, c.365A>G, c.492C>G, and c.662T>G) and destabilization of the protein structure (c.727C>T). The c.446-1G>T and c.380delG variants were verified to result in large alterations in the transcripts. Seven novel variations were identified, and the variant database for the SRD5A2 gene was expanded. These findings contribute to the progress of diagnostic and therapeutic approaches for individuals with SRD5A2 deficiency.
Humans ; 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Disorder of Sex Development, 46,XY/blood* ; Male ; Membrane Proteins/genetics* ; Child, Preschool ; Child ; Retrospective Studies ; Adolescent ; Female ; Mutation ; Testosterone/blood* ; Infant ; Dihydrotestosterone/blood*

OBJECTIVE: To retrospectively analyze the clinical data of newly diagnosed acute myeloid leukemia (AML) patients treated with venetoclax combined with azacitidine (Ven/Aza) or standard "3+7" regimen and similar regimens, collect real-world study data, compare the treatment response and adverse events between the two regimens, as well as perform survival analysis. METHODS: To retrospectively analyze the efficacy, survival, and adverse reactions of newly diagnosed AML patients treated with Ven/Aza (24 cases) and "3+7" regimens (117 cases ) in our hospital from September 2009 to March 2023, as well as factors influencing outcomes. A propensity score matching (PSM) was performed on age and Eastern Cooperative Oncology Group performance status (ECOG PS) to obtain a 1:1 matched cohort of 20 pairs, and the efficacy and survival before and after the matching were compared. RESULTS: The median age of patients in the Ven/Aza group was 69 years, while that in the "3+7" group was 56 years (P <0.001). Objective remission rate (ORR) was 62.5% in Ven/Aza group and 74.8% in "3+7" group (P >0.05). The median overall survival (OS) in the Ven/Aza group was 522 days, while that in the "3+7" group was 1 002 days (P >0.05). After controlling the two variables of age and ECOG PS, a PSM cohort of 20 pairs was obtained, in which the ORR was 65% in Ven/Aza group and 60% in "3+7" group (P >0.05). The median OS was 522 days and 629 days, and median progression-free survival (PFS) was 531 days and 198 days between the two groups, respectively. There were no statistically significant differences in OS and PFS between the two groups (both P >0.05). Additionally, the incidence of adverse events in the Ven/Aza group was significantly reduced. CONCLUSION The overall cohort shows that the "3+7" regimen has advantages in efficacy and survival, but Ven/Aza regimen is relatively safer. After performing PSM on age and ECOG PS, the Ven/Aza group showed improved efficacy, and a longer median PFS compared to "3+7" group.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Retrospective Studies ; Sulfonamides/administration & dosage* ; Azacitidine/administration & dosage* ; Bridged Bicyclo Compounds, Heterocyclic/administration & dosage* ; Aged ; Middle Aged ; Male ; Female ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Treatment Outcome

BACKGROUND: Temozolomide (TMZ) resistance is a significant challenge in treating glioblastoma (GBM). Collagen remodeling has been shown to be a critical factor for therapy resistance in other cancers. This study aimed to investigate the mechanism of TMZ chemoresistance by GBM cells reprogramming collagens. METHODS: Key extracellular matrix components, including collagens, were examined in paired primary and recurrent GBM samples as well as in TMZ-treated spontaneous and grafted GBM murine models. Human GBM cell lines (U251, TS667) and mouse primary GBM cells were used for in vitro studies. RNA-sequencing analysis, chromatin immunoprecipitation, immunoprecipitation-mass spectrometry, and co-immunoprecipitation assays were conducted to explore the mechanisms involved in collagen accumulation. A series of in vitro and in vivo experiments were designed to assess the role of the collagen regulators prolyl 4-hydroxylase subunit alpha 1 (P4HA1) and yes-associated protein (YAP) in sensitizing GBM cells to TMZ. RESULTS: This study revealed that TMZ exposure significantly elevated collagen type I (COL I) expression in both GBM patients and murine models. Collagen accumulation sustained GBM cell survival under TMZ-induced stress, contributing to enhanced TMZ resistance. Mechanistically, P4HA1 directly binded to and hydroxylated YAP, preventing ubiquitination-mediated YAP degradation. Stabilized YAP robustly drove collagen type I alpha 1 ( COL1A1) transcription, leading to increased collagen deposition. Disruption of the P4HA1-YAP axis effectively reduced COL I deposition, sensitized GBM cells to TMZ, and significantly improved mouse survival. CONCLUSION P4HA1 maintained YAP-mediated COL1A1 transcription, leading to collagen accumulation and promoting chemoresistance in GBM.
Temozolomide ; Humans ; Glioblastoma/drug therapy* ; Animals ; Mice ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics* ; YAP-Signaling Proteins ; Hydroxylation ; Dacarbazine/pharmacology* ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Collagen/biosynthesis* ; Collagen Type I/metabolism* ; Prolyl Hydroxylases/metabolism* ; Antineoplastic Agents, Alkylating/therapeutic use*