OBJECTIVE To investigate and analyze the pharmaceutical care needs of the elderly， thus providing a reference for improving the pharmaceutical care for the elderly. METHODS Based on the Kano model， a questionnaire was designed， and 1 200 community-dwelling elderly in the main urban area of Chongqing were selected as the survey subjects. The study analyzed the attributes and urgency of their pharmaceutical care needs to put forward optimization strategies. RESULTS A total of 1 200 questionnaires were distributed in the study， and 1 062 valid questionnaires were collected， with an effective response rate of 88.50%. The gender distribution of respondents was relatively balanced， with the majority aged between 60 and 69 （43.41%）， and generally possessing a relatively low level of educational attainment. The results showed that medication education and medication consultation were must-be needs； home-based pharmaceutical care was an expected need； drug reorganization， medication monitoring， pharmaceutical science popularization， and pharmaceutical ward round were attractive needs； internet-based pharmaceutical care was indifferent need. The urgent order of demand was medication education ＞ medication consultation ＞ home-based pharmaceutical care ＞ pharmaceutical science popularization ＞ drug reorganization ＞ medication monitoring ＞ pharmaceutical ward round ＞ internet-based pharmaceutical care. CONCLUSIONS The community elderly in Chongqing have high expectations for pharmaceutical care as a whole. Medical institutions should fully guarantee the two essential needs of medication education and medication consultation， and focus on ensuring the expected needs for home-based pharmaceutical care. Efforts should be made to develop the four attractive needs of pharmaceutical science popularization， drug reorganization， medication monitoring， and pharmaceutical ward round， and actively carry out age-friendly adaptations for internet-based pharmaceutical care.

Objective To evaluate the early efficacy and safety of the regimens containing delamanid and linezolid in the treatment of rifampicin resistant tuberculosis(RR-TB).Methods A total of 47 patients diagnosed with RR-TB at Public Health Clinical Center of Chengdu from August 2020 to December 2021 were enrolled,including 22 cases(46.8％)of multidrug-resistant tuberculosis(MDR-TB),8 cases(17.0％)of RR-TB,and 17 cases(36.2％)of pre-extensively drug-resistant tuberculosis(pre-XDR-TB).All patients were treated with a regimen based on delamanid and linezolid.The efficacy and safety were evaluated at 24 weeks of treatment.Results Among the 47 patients,46(97.9％)completed 24 weeks of treatment and 1(2.1％)was lost to follow-up.At 24 weeks,the sputum culture conversion rate was 100％in the 43 patients with positive baseline sputum culture.The median conversion time was 2(2,8)weeks.Imaging examination showed absorption in 46 patients(97.9％).Overall,40 patients(85.1％)experienced varying degrees of adverse events(AEs)within 24 weeks.Eleven patients(23.4％)experienced AEs possibly related to delamanid,mainly including QTcF interval prolongation(12.8％),gastrointestinal reactions(8.5％),dizziness(2.1％),headache(2.1％),and allergy(2.1％).Six patients permanently discontinued delamanid due to AEs including gastrointestinal reactions(6.4％),prolonged QTcF interval(2.1％),severe dizziness(2.1％),and drug allergy(2.1％).Patients with low baseline CD4+T lymphocyte counts(OR=0.991,95％CI:0.984-0.999)were more likely to experience delamanid-related AEs.Thirty patients(63.8％)experienced AEs possibly related to linezolid,including myelosuppression(55.3％),peripheral neuropathy(6.4％),optic neuritis occurred(2.1％),and allergy(2.1％).Three patients(6.4％)discontinued linezolid permanently due to severe anemia,peripheral neuropathy,and allergy.Conclusions The treatment regimens containing delamanid and linezolid for RR-TB showed a high sputum culture conversion rate and good tolerance at 24 weeks.Attention should be paid to gastrointestinal reactions and cellular immunity during treatment.

Objective To evaluate the early efficacy and safety of the regimens containing delamanid and linezolid in the treatment of rifampicin resistant tuberculosis(RR-TB).Methods A total of 47 patients diagnosed with RR-TB at Public Health Clinical Center of Chengdu from August 2020 to December 2021 were enrolled,including 22 cases(46.8％)of multidrug-resistant tuberculosis(MDR-TB),8 cases(17.0％)of RR-TB,and 17 cases(36.2％)of pre-extensively drug-resistant tuberculosis(pre-XDR-TB).All patients were treated with a regimen based on delamanid and linezolid.The efficacy and safety were evaluated at 24 weeks of treatment.Results Among the 47 patients,46(97.9％)completed 24 weeks of treatment and 1(2.1％)was lost to follow-up.At 24 weeks,the sputum culture conversion rate was 100％in the 43 patients with positive baseline sputum culture.The median conversion time was 2(2,8)weeks.Imaging examination showed absorption in 46 patients(97.9％).Overall,40 patients(85.1％)experienced varying degrees of adverse events(AEs)within 24 weeks.Eleven patients(23.4％)experienced AEs possibly related to delamanid,mainly including QTcF interval prolongation(12.8％),gastrointestinal reactions(8.5％),dizziness(2.1％),headache(2.1％),and allergy(2.1％).Six patients permanently discontinued delamanid due to AEs including gastrointestinal reactions(6.4％),prolonged QTcF interval(2.1％),severe dizziness(2.1％),and drug allergy(2.1％).Patients with low baseline CD4+T lymphocyte counts(OR=0.991,95％CI:0.984-0.999)were more likely to experience delamanid-related AEs.Thirty patients(63.8％)experienced AEs possibly related to linezolid,including myelosuppression(55.3％),peripheral neuropathy(6.4％),optic neuritis occurred(2.1％),and allergy(2.1％).Three patients(6.4％)discontinued linezolid permanently due to severe anemia,peripheral neuropathy,and allergy.Conclusions The treatment regimens containing delamanid and linezolid for RR-TB showed a high sputum culture conversion rate and good tolerance at 24 weeks.Attention should be paid to gastrointestinal reactions and cellular immunity during treatment.

Objective:To analyze the distribution and drug resistance of the pathogen of bloodstream infections in patients with malignancies in Shanxi Province Cancer Hospital.Methods:A retrospective case series study was conducted. A total of 8 654 patients with malignancies whose blood culture was detected in Shanxi Province Cancer Hospital between January 2019 and December 2021 were collected, and venous blood was drawn for blood culture. WHONET 5.6 software and SPSS 23.0 software were used to analyze the distribution and drug resistance of the pathogen of bloodstream infections.Results:A total of 600 (6.9%) pathogens were isolated, including 413 (68.8%) strains of Gram-negative bacteria, 168 (28.0%) strains of Gram-positive bacteria, 19 (3.2%) strains of fungi. The top 5 gram-negative bacteria were Escherichia coli (37.7%), Klebsiella pneumoniae (14.2%), Enterobacter cloacae (4.5%), Pseudomonas aeruginosa (3.0%), and Acinetobacter baumannii (2.5%). The top 5 gram-positive bacteria were Staphylococcus aureus (4.2%), Enterococcus faecium (4.0%), Staphylococcus hominis (3.8%), Staphylococcus epidermidis (3.5%) and Streptococcus (3.0%); except Klebsiella pneumoniae, there were no statistically significant differences in the composition ratio of other major pathogens from 2019 to 2021 (all P > 0.05). The resistance rates of Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae to ampicillin were 94.7% (214/226), 100.0% (85/85) and 96.3% (26/27); the resistance rates of those to ciprofloxacin were 61.9% (140/226), 17.6% (15/85) and 7.4% (2/27); and the resistance rates of those to cefoperazone were 62.4% (141/226), 30.6% (26/85) and 25.9% (7/27), respectively. The resistance rates of P. aeruginosa and Acinetobacter baumannii to carbapenems were 5.5% (1/18) and 93.3% (14/15). Staphylococcus aureus, Staphylococcus hominis, Staphylococcus epidermidis were predominantly Staphylococcus. Enterococcus faecium and Enterococcus faecalis were the main types of enterococcus. Positive blood culture samples were mainly distributed in hematology department and intensive care unit. Non-Hodgkin lymphoma (39 strains) and acute myeloid leukemia (12 strains) were the main diseases. Conclusions:The main pathogen of bloodstream infection in patients with malignancies in this area is Gram-negative bacteria, and drug resistance is common. Hospitals should rationally use antibiotics by combining with drug sensitivity test.

Objective:To explore the genetic etiology of a fetus with short limbs identified by prenatal ultrasonography.Methods:A fetus detected with short limb malformations at Shengjing Hospital Affiliated to China Medical University on October 25, 2021 was selected as the study subject. Prenatal ultrasound and post-abortion imaging were carried out to determine the phenotypic characteristics of the fetus. Amniotic fluid sample of the fetus and peripheral blood samples of its parents were collected. Following extraction of genomic DNA, whole-exome sequencing was carried out. Candidate variants were verified by Sanger sequencing. Online software was used to predict the structural changes of the mutant proteins.Results:Prenatal ultrasound showed that the fetus had a small bell-shaped thorax, markedly shortened limbs, flat midface, a small nose with anteriorly tilted nostrils, and a small mandible. Post-abortion CT showed typical short and wide fetal ribs, cupped metaphyses at both ends, short long bones with wide metaphyses, resulting in a dumbbell-shaped appearance and curved thoracic vertebrae. Whole-exome sequencing revealed that the fetus had harbored compound heterozygous variants of the COL11A1 gene, namely c. 2251G>T and c. 3790G>T, both of which were predicted to alter the important Gly-X-Y structure of collagen protein. Sanger sequencing confirmed that the variants were respectively inherited from its parents. Conclusion:A rare fetus with Fibrochondrogenesis type 1 due to compound heterozygous variants of the COL11A1 gene has been diagnosed. Above finding has enabled genetic counseling and reproductive guidance for this family.

Objective:To construct a prognostic model for lung squamous cell carcinoma (SqCLC) based on autophagy-related genes analyzed by bioinformatics and validate it.Methods:Expression profile data and clinical information of 268 SqCLC patients were downloaded from The Cancer Genome Atlas (TCGA) database and a dataset of normal lung tissues of 336 healthy people was downloaded from the Genotype Tissue Expression (GTEx) database; the autophagy-related genome was obtained from the GO_AUTOPHAGY genome of the Human Autophagy Database (HADb) and the Molecular Signature Database (MSigDB) 6.2. R 4.0.3 software was applied to analyze the differentially expressed genes between SqCLC tissues in TCGA database and normal lung tissues in GTEx database. Screening of autophagy-related genes differentially expressed between SqCLC tissues and normal lung tissues in the TCGA database (referred to as differentially expressed autophagy genes) was performed using R 4.0.3 software. The Cox proportional risk model was applied to analyze the relationship between the differentially expressed autophagy genes and prognosis of SqCLC patients in TCGA database, and a prognostic model was constructed. The SqCLC patients in TCGA database were divided into high-risk group and low-risk group based on the median risk score of the prognostic model, and the Kaplan-Meier method was used to compare the overall survival of the two groups; the time-dependent receiver operating characteristic (ROC) curve of the 3-, 5- and 10-year overall survival rates of 268 patients in TCGA database predicted by the prognostic model was plotted. Cox regression was used to analyze the independent influencing factors of overall survival of SqCLC patients in TCGA database, and the prognostic index formula was established. Based on the consistency index and restricted mean survival (RMS) curve, the predictive efficacy for the survival of patients in TCGA database between prognostic index of prognostic model risk score alone and prognostic index of risk score combined with independent influencing factors was compared. R 4.0.3 software was used to construct the nomogram for predicting patients' 3-, 5- and 10-year overall survival rates.Results:Six prognosis related differentially expressed autophagy genes were screened, and a prognostic model was constructed as: risk score=PEX14×0.337+CASPASE-8×(-0.280)+TM9SF1×0.292+UBB×0.472+P4HB×0.163+CTSA×0.173. In TCGA database, the overall survival of high-risk group was worse than that of low-risk group ( P < 0.001). Time-dependent ROC curve analysis showed that the area under the curve (AUC) of the prognostic model risk score for predicting the 3-, 5- and 10-year overall survival rates of 268 patients in TCGA database was 0.715, 0.715 and 0.831, respectively. Multivariate Cox regression analysis showed that age, staging and prognostic model risk score were independent factors affecting the overall survival of SqCLC patients in TCGA database, and the prognostic index=0.998×risk score+0.725×staging+0.559×age. The RMS curve showed that compared with the prognostic model risk score, the prognostic index combined with 3 independent prognostic factors had a better effect on predicting the overall survival (consistency index: 0.68 vs. 0.65, P =0.045). Using age, staging and prognostic model risk score, a nomogram was constructed to predict the survival of patients with SqCLC, and its calibration curve was close to the ideal curve. Conclusions:A prognostic model of SqCLC based on 6 characteristic differentially expressed autophagy-related genes has been successfully established. Internal validation shows that this model combined with other clinicopathological factors could be helpful in predicting the survival of SqCLC patients.

Changes in structure of oral solid dosage forms (OSDF) elementally determine the drug release and its therapeutic effects. In this research, synchrotron radiation X-ray micro-computed tomography was utilized to visualize the 3D structure of enteric coated pellets recovered from the gastrointestinal tract of rats. The structures of pellets in solid state and in vitro compendium media were measured. Pellets in vivo underwent morphological and structural changes which differed significantly from those in vitro compendium media. Thus, optimizations of the dissolution media were performed to mimic the appropriate in vivo conditions by introducing pepsin and glass microspheres in media. The sphericity, pellet volume, pore volume and porosity of the in vivo esomeprazole magnesium pellets in stomach for 2 h were recorded 0.47, 1.55 × 10⁸ μm³, 0.44 × 10⁸ μm³ and 27.6%, respectively. After adding pepsin and glass microspheres, the above parameters in vitro reached to 0.44, 1.64 × 10⁸ μm³, 0.38 × 10⁸ μm³ and 23.0%, respectively. Omeprazole magnesium pellets behaved similarly. The structural features of pellets between in vitro media and in vivo condition were bridged successfully in terms of 3D structures to ensure better design, characterization and quality control of advanced OSDF.

Defining and visualizing the three-dimensional (3D) structures of pharmaceuticals provides a new and important tool to elucidate the phenomenal behavior and underlying mechanisms of drug delivery systems. The mechanism of drug release from complex structured dosage forms, such as bilayer osmotic pump tablets, has not been investigated widely for most solid 3D structures. In this study, bilayer osmotic pump tablets undergoing dissolution, as well as after dissolution in a desiccated solid state were examined, and visualized by synchrotron radiation micro-computed tomography (SR-μCT). In situ formed 3D structures at different in vitro drug release states were characterized comprehensively. A distinct movement pattern of NaCl crystals from the push layer to the drug layer was observed, beneath the semi-permeable coating in the desiccated tablet samples. The 3D structures at different dissolution time revealed that the pushing upsurge in the bilayer osmotic pump tablet was directed via peripheral "roadways". Typically, different regions of the osmotic front, infiltration region, and dormant region were classified in the push layer during the dissolution of drug from tablet samples. According to the observed 3D microstructures, a "subterranean river model" for the drug release mechanism has been defined to explain the drug release mechanism.

Effective methods for visualizing neurovascular morphology are essential for understanding the normal spinal cord and the morphological alterations associated with diseases. However, ideal techniques for simultaneously imaging neurovascular structure in a broad region of a specimen are still lacking. In this study, we combined Golgi staining with angiography and synchrotron radiation micro-computed tomography (SRμCT) to visualize the 3D neurovascular network in the mouse spinal cord. Using our method, the 3D neurons, nerve fibers, and vasculature in a broad region could be visualized in the same image at cellular resolution without destructive sectioning. Besides, we found that the 3D morphology of neurons, nerve fiber tracts, and vasculature visualized by SRμCT were highly consistent with that visualized using the histological method. Moreover, the 3D neurovascular structure could be quantitatively evaluated by the combined methodology. The method shown here will be useful in fundamental neuroscience studies.

Effective methods for visualizing neurovascular morphology are essential for understanding the normal spinal cord and the morphological alterations associated with diseases. However, ideal techniques for simultaneously imaging neurovascular structure in a broad region of a specimen are still lacking. In this study, we combined Golgi staining with angiography and synchrotron radiation micro-computed tomography (SRμCT) to visualize the 3D neurovascular network in the mouse spinal cord. Using our method, the 3D neurons, nerve fibers, and vasculature in a broad region could be visualized in the same image at cellular resolution without destructive sectioning. Besides, we found that the 3D morphology of neurons, nerve fiber tracts, and vasculature visualized by SRμCT were highly consistent with that visualized using the histological method. Moreover, the 3D neurovascular structure could be quantitatively evaluated by the combined methodology. The method shown here will be useful in fundamental neuroscience studies.
Animals ; Imaging, Three-Dimensional ; Mice ; Neural Networks, Computer ; Spinal Cord/diagnostic imaging* ; Synchrotrons ; X-Ray Microtomography