OBJECTIVE To explore the role of clinical pharmacists in identifying paroxysmal spasms caused by drugs， and provide reference for rational drug use. METHODS Retrospective analysis was conducted on pharmaceutical care provided by clinical pharmacists for a patient with ceftazidime-avibactam （CZA-AVI） induced paroxysmal spasms. The clinical pharmacists identified， analyzed and summarized the clinical manifestations， risk factors and treatment methods of the nervous system toxicity caused by antibacterial drugs. According to the patient’s clinical symptoms and test results， the clinical pharmacists recommended temporarily discontinuing the use of polymyxin B and montelukast sodium， and halving the dose of CZA-AVI. The physicians did not adopt the recommendation to halve the dose of CZA-AVI， and when the patient’s neurologic toxicity did not improve， the clinical pharmacists again recommended discontinuing CZA-AVI， which was accepted by the physicians. RESULTS Clinical pharmacists analyzed the condition and checked related drugs that caused paroxysmal spasms of extremities one by one， and finally determined that CZA-AVI might be the drug that caused paroxysmal spasms of extremities in the patient. After stopping the drug， the patient’s symptoms improved and was transferred to a community hospital for rehabilitation treatment. CONCLUSIONS The dose of CZA-AVI should be adjusted according to the renal function and the neurotoxicity should be guarded against， especially for patients with advanced age， renal insufficiency， and the combined use of multiple drugs related to nephrotoxicity and neurotoxicity.

Background::Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods::A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance.Results::All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. Conclusions::The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.

Endocrine-resistance remains a major challenge in estrogen receptor α positive (ERα⁺) breast cancer (BC) treatment and constitutively active somatic mutations in ERα are a common mechanism. There is an urgent need to develop novel drugs with new mode of mechanism to fight endocrine-resistance. Given aberrant ERα activity, we herein report the identification of novel covalent selective estrogen receptor degraders (cSERDs) possessing the advantages of both covalent and degradation strategies. A highly potent cSERD 29c was identified with superior anti-proliferative activity than fulvestrant against a panel of ERα⁺ breast cancer cell lines including mutant ERα. Crystal structure of ERα‒ 29c complex alongside intact mass spectrometry revealed that 29c disrupted ERα protein homeostasis through covalent targeting C530 and strong hydrophobic interaction collied on H11, thus enforcing a unique antagonist conformation and driving the ERα degradation. These significant effects of the cSERD on ERα homeostasis, unlike typical ERα degraders that occur directly via long side chains perturbing the morphology of H12, demonstrating a distinct mechanism of action (MoA). In vivo, 29c showed potent antitumor activity in MCF-7 tumor xenograft models and low toxicity. This proof-of-principle study verifies that novel cSERDs offering new opportunities for the development of innovative therapies for endocrine-resistant BC.

Objective:To assess the combination of conventional ultrasound with contrast-enhanced ultrasound(CEUS)in the diagnosis of urothelial carcinoma(UC)of the renal pelvis in elderly patients.Methods:Sixty-seven elderly patients with a histopathologic diagnosis of UC of the renal pelvis and surgically treated at our hospital between April 2015 and March 2023 were retrospectively analyzed.Characteristics of regular preoperative 2D ultrasound, color Doppler flow imaging(CDFI)and CEUS were examined.Results:Of 67 patients, 49(73.13%)were found to have localized lesions in the renal pelvis and renal calyces.Lesions in 53 patients(79.10%)could be clearly identified by conventional ultrasound, with 46(86.79%)being isoechoic or hypoechoic, and 7(13.21%)being hyperechoic.Analysis of tumor blood flow by CDFI found 22 cases(41.51%)with avascular lesions, 21(39.62%)with hypovascular lesions and 10(18.87%)with hypervascular lesions.The average value of the resistance index(RI)was 0.64.Enhancement was seen in 62 lesions(92.54%)by CEUS after injection of SonoVue.Compared with the cortex of the ipsilateral kidney, a slow enhancement pattern was observed in 46(74.19%), 14(22.58%)showed simultaneous enhancement, and 2(3.23%)showed fast enhancement.At peak enhancement, 43 lesions(69.35%)had hypo-enhancement, 10(16.13%)had iso-enhancement, and 9(14.52%)had hyper-enhancement, compared with the cortex.Concerning the homogeneity of enhancement, 16(25.81%)displayed heterogeneous enhancement, with tumor necrosis or hemorrhage, and 46(74.19%)had homogeneous enhancement.When the contrast agent washout rate was assessed, a fast washout pattern was observed in 53(85.48%), synchronous washout in 6(9.68%), and slow washout in 3(4.84%).Conclusions:UC of the renal pelvis mostly shows isoechoic and hypoechoic lesions on conventional ultrasound, avascular or hypo-vascular lesions on CDFI, and slow-in, fast-out and hypo-enhancement on CEUS, compared with the cortex.Conventional ultrasound combined with CEUS can help improve the diagnostic accuracy of UC of the renal pelvis.

Objective:To investigate the effect of autologous hematopoietic stem cell transplantation (auto-HSCT) bridging to chimeric antigen receptor T cell (CAR-T) immunotherapy for follicular lymphoma (FL) transformed to B-lymphoblastic leukemia/lymphoma (B-LBL).Methods:The diagnosis and treatment of 1 patient with FL transformed to B-LBL admitted to the First Hospital of Soochow University in August 2020 were retrospectively analyzed and the literature was reviewed.Results:The male patient was 65 years old, and was diagnosed as FL (stage Ⅳ group A, FL international prognostic index -1 score 3 points, high-risk group) in August 2020. And then he was given 6 courses of RB (rituximab combined with bendamustine) regimen, with complete remission (CR) at mid-term and end-stage PET-CT, followed by regular maintenance therapy with rituximab every 2 months, and disease progressed after 4 courses of maintenance therapy. According to the results of histopathology and bone marrow aspiration in December 2021, he was diagnosed B-LBL involving the bone marrow. Partial remission was achieved after induction therapy with zanubnulindb combined with hyper CVAD (cyclophosphamide + doxorubicin + vindesine + dexamethasone) regimen, followed by auto-HSCT bridging to CAR-T treatment targeting CD19 and CD22, which proceeded smoothly with cytokine release syndrome grade 0, immune effector cell-associated neurotoxicity syndrome grade 0. The patient successfully underwent hematopoietic reconstruction and orally taken ibrutinib after discharge. PET-CT indicated CR 2 months after transplantation and he was still in disease-free survival state.Conclusions:The prognosis of FL transformed to B-LBL is poor, and auto-HSCT bridging to CAR-T can improve the prognosis and prolong the survival time of patients who cannot undergo allogeneic hematopoietic stem cell transplantation.

To explore the pharmacogenomic markers that affect the platinum-based chemotherapy response in non-small-cell lung carcinoma (NSCLC), we performed a two-cohort of genome-wide association studies (GWAS), including 34 for WES-based and 433 for microarray-based analyses, as well as two independent validation cohorts. After integrating the results of two studies, the genetic variations related to the platinum-based chemotherapy response were further determined by fine-mapping in 838 samples, and their potential functional impact were investigated by eQTL analysis and in vitro cell experiments. We found that a total of 68 variations were significant at P < 1 × 10^-3 in cohort 1 discovery stage, of which 3 SNPs were verified in 262 independent samples. A total of 541 SNPs were significant at P < 1 × 10^-4 in cohort 2 discovery stage, of which 8 SNPs were verified in 347 independent samples. Comparing the validated SNPs in two GWAS, ADCY1 gene was verified in both independent studies. The results of fine-mapping showed that the G allele carriers of ADCY1 rs2280496 and C allele carriers of rs189178649 were more likely to be resistant to platinum-based chemotherapy. In conclusion, our study found that rs2280496 and rs189178649 in ADCY1 gene were associated the sensitivity of platinum-based chemotherapy in NSCLC patients.

Objective:This study aimed to compare the efficacy and safety of cladribine, smustine, etoposide, cyclophosphamide, and cytarabine (C+SCAV) and smustine, etoposide, cytarabine, and melphalan (SEAM) conditioning regimens in autologous stem cell transplantation (auto-HSCT) for non-Hodgkin’s lymphoma (NHL) .Methods:A retrospective analysis was conducted on 61 NHL patients who received auto-HSCT in the Department of Hematology, the First Affiliated Hospital of Suzhou University, from March 2018 to May 2021. The C + SCAV group and SEAM group had 19 and 42 patients, respectively.Results:① Among the 61 patients with NHL, 37 were male and 24 were female. The median age was 48 (21-66) years old. There were 19 cases in the C+SCAV group and 42 cases in the SEAM group. There was no significant difference in the baseline characteristics between the two groups ( P>0.05) . ② The median time to neutrophil and platelet engraftment in the C+SCAV cohort were 10 (8-15) days and 13 (9-22) days, respectively, which does not differ from the SEAM group ( P=0.103, P=0.403) . ③ No differences existed between the two groups in terms of survival. The 1-year progression-free survival (PFS) was (76.5±10.3) % for patients receiving C+SCAV and (78.4±6.8) % for those who received SEAM ( P=0.841) . The 1-year overall survival was 100.0% for the C+SCAV group and 95.2±3.3% for the SEAM group ( P=0.339) . ④The 1-year PFS of patients with complete remission in the C+SCAV group was similar to those who in the SEAM group [ (92.3±7.4) % vs (82.5±7.2) %, P=0.406]. ⑤ The incidence of non-hematological serious adverse events (≥ grade 3) in the C+SCAV group and SEAM group were 10.5% (2/19) and 40.5% (17/42) ( P=0.013) , the incidence of severe mucositis was 5.3% (1/19) and 31.0% (13/42) ( P=0.015) , and the incidence of severe infection (≥ grade 3) was 10.5% (2/19) and 19.0% (8/42) ( P=0.389) , respectively. Conclusion:C + SCAV conditioning regimen appeared to be no different from the SEAM regimen in terms of survival. It can lower the incidence of SAE and does not increase the risk of severe infection. As a result, it can be used as an alternative conditioning regimen for lymphoma patients undergoing auto-HSCT.

Objective: To predict the in-hospital incidence of acute respiratory distress syndrome (ARDS) in COVID-19 patients by developing a predictive nomogram. Methods: Patients with COVID-19 admitted to Changsha Public Health Centre between 30 January 2020, and 22 February 2020 were enrolled in this study. Clinical characteristics and laboratory variables were analyzed and compared between patients with or without ARDS. Clinical characteristics and laboratory variables that were risk factors of ARDS were screened by the least absolute shrinkage and selection operator binary logistic regression. Based on risk factors, a prediction model was established by logistic regression and the final nomogram prognostic model was performed. The calibration curve was applied to evaluate the consistency between the nomogram and the ideal observation. Results: A total of 113 patients, including 99 non-ARDS patients and 14 ARDS patients were included in this study. Eight variables including hypertension, chronic obstructive pulmonary disease, cough, lactate dehydrogenase, creatine kinase, white blood count, body temperature, and heart rate were included in the model. The area under receiver operating characteristic curve, specificity, sensitivity, and accuracy of the full model were 0.969, 1.000, 0.857, and 0.875, respectively. The calibration curve also showed good agreement between the predicted and observed values in the model. Conclusions: The nomogram can be used to predict the in-hospital incidence of ARDS in COVID-19 patients.

Objective:In order to analyze the current research status of handover shift in nursing management, summarize, analyze and judge the existing literature, in order to provide reference for clinical nursing practice.Methods:Through literature review, it is planned to review the current situation, shortcomings and future development of nursing handover classes.Results:The handover process was generally divided into four stages, of which SBAR was the best practice tool for handing over key information. For the performance of handover shifts, NASR, PVNC-BR, HES and Handoff CEX were often used to evaluate the performance of shifts, and for the results of shifts, evaluations were mostly conducted at the levels of patient safety, process elements, and organizational management. At present, the use of electronic information systems, benign organizational culture and patient and family-centered clinical practice could effectively improve the efficiency and effectiveness of handover.Conclusions:The process and elements of the current shift mode are relatively complete, and the communication strategy is reasonable, but there are still many shortcomings and defects. This suggests that nursing managers should adopt scientific intervention methods and evaluation tools when paying attention to and reforming nursing handover in the future to continuously improve the quality of handover.

Biosynthesis of nanomaterials has attracted much attention for its excellent characteristics such as low energy consumption, high safety, and environmental friendliness. As we all know, the toxic selenite can be transformed into higher-value nanomaterials by using bacteria. In this study, nano-selenium was synthesized by halophilic Bacillus subtilis subspecies stercoris strain XP in LB medium supplemented with selenite (electron acceptor). The physicochemical characteristics of nano-selenium were analyzed by scanning electron microscope (SEM), X-ray energy dispersive spectral analysis (EDAX), X-ray diffraction (XRD), and fourier transform infrared spectroscopy (FTIR). Meanwhile, the antifungal activity of nano-selenium to strawberry pathogens (fusarium wilt, erythema, and purple spot fungi) was determined. The products from reduction of selenite by strain XP was amorphous spherical selenium nanoparticles (SeNPs) with a diameter range of 135-165 nm. The production of SeNPs was positively correlated with time (0-48 h) and no changes were observed on cell morphology. Selenium was dominant in the surface of SeNPs where the organic elements (C, O, N, and S) existed at the same time. SeNPs were coated with biomolecules containing functional groups (such as -OH, C=O, N-H, and C-H) which were associated with the stability and bioactivity of particles. Although the highest concentration of SeNPs had significant (P<0.05) inhibitory effects on three strains of strawberry pathogens, antifungal activity to erythema and fusarium wilt pathogenic fungi was higher than that to purple spot pathogenic fungi from strawberry. In conclusion, strain XP not only has strong tolerance to high salt stress, but can be also used to synthesize biological SeNPs with good stability and biological activity. Thus, the strain XP has bright perspectives and great potential advantage in pathogens control and green selenium-rich strawberry planting as well as other fields.
Bacillus subtilis ; Fragaria ; Nanoparticles ; Selenious Acid ; Selenium