AIM:To investigate the mechanism through which esculetin induces ferroptosis of mouse breast cancer 4T1 cells.METHODS:Molecular docking of esculetin with p53,solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4)proteins was performed,and Kaplan-Meier curves and time-dependent receiver oper-ating characteristic curves were drawn.The 4T1 cells were divided into 6 groups,namely the control(CON),1/2 IC50,IC50,2 IC50,erastin,and capecitabine groups.The appropriate drug concentration for treating 4T1 cells was screened by CCK-8 assay.The invasion and migration abilities of 4T1 cells following esculetin treatment at the selected drug concentra-tion were analyzed by scratch test and Transwell assay.Mitochondrial morphological change were examined by electron mi-croscopy.The levels of ferroptotic cell death were then quantified by Fe2+,reactive oxygen species(ROS),malondialde-hyde(MDA),glutathione(GSH),and GPX4 assays.Western blot was performed to evaluate the protein levels of p53,SLC7A11,GPX4 and acyl-CoA synthetase long-chain family member 4(ACSL4).RESULTS:Compared with CON group,the esculetin 1/2 IC50,IC50 and 2 IC50 groups showed smaller size,increased membrane density,and decreased ridge of mitochodria,as well as decreased levels of GSH and GPX4,reduced cell invasion and migration abilities,and de-creased levels of SLC7A11 and GPX4 proteins(P＜0.05).Furthermore,these groups exhibited increased levels of Fe2+,ROS,and MDA,as well as elevated p53 and ACSL4 protein abundance(P＜0.05).CONCLUSION:Esculetin pro-motes ferroptosis of 4T1 cells through a mechanism involving the p53/SLC7A11/GPX4 regulatory axis.

OBJECTIVE To explore the specific application and evaluation effect of objective structured clinical examination(OSCE)-guided scenario-based practical teaching mode in training clinical pharmacists. METHODS Fifty-six trainees who participated in the clinical pharmacist training program in the Second Xiangya Hospital of Central South University from October 2020 to September 2022 were selected as the research objects. OSCE-guided teaching was conducted, and the application effect of OSCE-guided teaching mode in clinical pharmacist training was explored and analyzed by using theoretical examination results and OSCE assessment results as evaluation indicators. RESULTS Through comparative analysis, it was found that the OSCE-guided teaching mode not only enabled students to better grasp the theoretical knowledge points required by the training outline, but also improved their clinical thinking ability, problem-solving ability, and communication and coordination skills to varying degrees. CONCLUSION For clinical pharmacist trainees, the OSCE teaching mode is conducive to the comprehensive improvement of clinical pharmacist skills and is suitable for cultivating clinical pharmacists who are capable of independently carrying out clinical pharmacy services in the new situation.

Objective:To establish a prediction model for symptomatic radiation pneumonitis (SRP) after radiotherapy for thoracic cancer based on a longitudinal cohort and dose interval variations.Methods:Clinical data of 587 patients who received thoracic radiotherapy in Department of Radiotherapy of Yunnan Cancer Hospital from July 2022 to June 2023 were retrospectively analyzed. The National Cancer Institute common terminology criteria for adverse events (CTCAE) version 5.0 was used to grade radiation pneumonitis, and clinical factors, traditional independent dosimetric characteristics and dose interval variation characteristics were collected. Features used to predict the occurrence of SRP were screened using genetic algorithms and analyzed the correlation between the selected features and SRP occurrence. Predictive models for SRP occurrence were established using the selected features and evaluated, and the optimal predictive model was visualized using a column chart.Results:The incidence of SRP was 35.94%. Five clinical factors, seven independent dosimetric features and six dose interval variation features were screened out by genetic algorithms to effectively predict the occurrence of SRP. The area under ROC curve (AUC) of clinical factors combined with traditional independent dosimetric factors and dose interval variation factors was 76%. The AUC of clinical factors combined with traditional independent dosimetric factors and that of clinical factors combined with dose interval variation factors was 69% and 67%, respectively. The addition of the characteristics of dose interval variation factors significantly improved the effectiveness of the prediction model.Conclusions:The supplement of the characteristics of dose interval variation factors can significantly improve the performance of the SRP prediction model for thoracic tumors after radiotherapy. The SRP prediction model based on dose interval variations can effectively predict the occurrence of SRP.

Acute kidney injury (AKI) is an important factor for the occurrence and development of CKD. The protective effect of dihydroartemisinin on AKI and and reported mechanism have not been reported. In this study, we used two animal models including ischemia-reperfusion and UUO, as well as a high-glucose-stimulated HK-2 cell model, to evaluate the protective effect of dihydroartemisinin on premature senescence of renal tubular epithelial cells in vitro and in vivo. We demonstrated that dihydroartemisinin improved renal aging and renal injury by activating autophagy. In addition, we found that co-treatment with chloroquine, an autophagy inhibitor, abolished the anti-renal aging effect of dihydroartemisinin in vitro. These findings suggested that activation of autophagy/elimination of senescent cell might be a useful strategy to prevent AKI/UUO induced renal tubular senescence and fibrosis.
Animals ; Kidney ; Acute Kidney Injury/chemically induced* ; Ischemia ; Reperfusion Injury/drug therapy* ; Autophagy ; Reperfusion

OBJECTIVE：To provide reference for constructing and improving the pharmacovigilance signal management sys - tem in China by comparing signal management system among the European Union （EU），the United States （U. S. ）and Japan. METHODS：Literature analysis method was used to systematically compare the similarities and differences on definitions ，sources， detection methods and management process of pharmacovigilance signals among EU ，U. S. and Japan. Some suggestions were put forward for pharmacovigilance management in China. RESULTS & CONCLUSIONS ：Regulatory authorities of the EU ，U. S. and Japan did not have a uniform definition on signals ；EU drug administration adopted the definition of the eighth working group of Council for International Organizations of Medical Sciences ，FDA adopted its own definition ，while the Japanese regulatory agency had no clear definition. Currently ，post-marketing surveillance still relied mainly on spontaneous reporting systems ；EU，U. S. and Japan had carried out the signal detection based on the spontaneous reporting system ；EU mainly adopted the proportional reporting ratio method ，U. S. mainly adopts the multiple gamma Poisson Shrinker ，and Japan mainly adopted the reporting ratio method. EU had special guidelines for signal management process ，while the U. S. and Japan did not. It is recommended to accelerate the deve- lopment of the legal and regulatory framework on pharmacovigilance in China ，draw up guidelines on pharmacovigilance practices ， strengthen the active ADR surveillance and promote the application of data mining techniques in signal detection field ，for accelerat - ing the standardization and internationalization of China ’s pharmacovigilance work.

Drug delivery with customized combinations of drugs, controllable drug dosage, and on-demand release kinetics is critical for personalized medicine. In this study, inspired by successive opening of layered structures and compartmentalized structures in plants, we designed a multiple compartmentalized capsular structure for controlled drug delivery. The structure was designed as a series of compartments, defined by the gradient thickness of their external walls and internal divisions. Based on the careful choice and optimization of bioinks composed of gelatin, starch, and alginate, the capsular structures were successfully manufactured by fused deposition modeling three-dimensional (3D) printing. The capsules showed fusion and firm contact between printed layers, forming complete structures without significant defects on the external walls and internal joints. Internal cavities with different volumes were achieved for different drug loading as designed. In vitro swelling demonstrated a successive dissolving and opening of external walls of different capsule compartments, allowing successive drug pulses from the capsules, resulting in the sustained release for about 410 min. The drug release was significantly prolonged compared to a single burst release from a traditional capsular design. The bioinspired design and manufacture of multiple compartmentalized capsules enable customized drug release in a controllable fashion with combinations of different drugs, drug doses, and release kinetics, and have potential for use in personalized medicine.

Objective To study the effect of COVID-19 pandemic on the stroke center of Yongchuan Hospital Affiliated to Chongqing Medical University（“our hospital” for short），so as to provide reference for the stroke center to cope with COVID-19 pandemic.Methods 161 stroke patients in our hospital from January 24 to March 10，2020（the first level response period for major public health emergencies in Chongqing） were selected as the pandemic group. 259 stroke patients in our hospital from February 4 to March 23，2019（the same period in the lunar calendar with 2020）were selected as non pandemic group，and the clinical data of the two groups were compared.Results The time of visiting hospital and the ratio of ischemic stroke patients in pandemic group were lower than those in non pandemic group，and the emergency visiting rate，calling ambulance rate，hospitalization rate，hospitalization days，critical ill rate，special or primary nursing rate were higher than those in non pandemic group（P<0.05）；there was no statistical significance between the two groups in gender and age（P>0.05）.Between the emergency visiting patients of the two groups，There was no significant difference in the time of visiting hospital（P>0.05）.Between the ischemic stroke patients of the two groups，time from door to puncture in thrombectomy（DTP） in pandemic group was lower than that in non pandemic group（P<0.05），There was no significant difference in the National Institute of Health Stroke Scale（NIHSS score），thrombolysis rate，time from door-to-needle in thrombolysis（DNT），and Endovascular therapy rate（P>0.05）.Between the Hemorrhagic stroke patients of the two groups，The emergency operation rate in pandemic group was higher than that in the non pandemic group，and the time from admission to emergency operation in pandemic was shorter than that in the non pandemic group.Conclusion During the period of COVID-19 pandemic，the patients in the stroke center showed the following characteristics compared with normal：the number of visiting hospital was reduced，the time of visiting hospital was shortened，the degree of illness was aggravated，the hospitalization rate was increased，the hospitalization days were increased，the ischemic stroke ratio was reduced，the DTP of ischemic stroke was shortened，the emergency operation rate of hemorrhagic stroke was increased，and the time from admission to emergency operation of hemorrhagic stroke was shortened.

Objective To explore the therapeutic effect and clinical significance of pelvic floor rehabilitation technique in female with myofascial chronic pelvic pain (MCPP) by detecting the pressure pain thresholds (PPTs). Methods One hundred healthy female (control group) and 324 female MCPP patients (observation group) from January 2009 to December 2016 were selected. Automatic body surface and vaginal pressure pain detector was applied to detect two groups′PPTs of the 34 spots. The difference of PPTs at each spot was analyzed in two groups. In addition, 51 patients with moderate and severe MCPP were selected to record the changes of PPTs and pain scores before and after the treatment of pelvic floor rehabilitation technique. Results The average PPTs of the abdomen, vulva, pelvic floor and vaginal front and back fornix, bilateral adnexa uteri and sacrouterine ligament in the observation group were significantly lower than those in the control group (P<0.01 or<0.05). The average PPTs of the abdomen, vulva, pelvic floor muscles and vaginal front and back fornix, bilateral adnexa uteri and sacrouterine ligament of 51 MCPP patients after treatment were significantly higher than those before treatment (P<0.01). After treatment, PPTs and pain scores of the pelvic floor muscles, bilateral adnexa uteri, bilateral sacrouterine ligament, bilateral sacral spine ligament and vaginal front and back fornix were negatively correlated (r =- 0.78 to- 0.19, P = 0.01 to 0.04); there was a negative correlation between the PPTs and pain scores of the left and right latissimus dorsi (r=-0.28, P=0.04;r=-0.32, P=0.02). The complete remission rate with the pelvic floor rehabilitation technique in 51 patients with MCPP was 9.8％(5/51), the significant remission rate was 90.2％(46/51), and the total remission rate was 100.0％ (51/51). Conclusions Compared with the normal healthy ones, female with MCPP has lower PPTs in the abdomen, perineum, vagina and pelvic floor. The effect of pelvic floor rehabilitation technique on MCPP is well, which can increase patients′PPTs to reduce pain scores. It is a worthwhile method to treat these diseases.

Objective: To explore the clinical features, the serotype distribution and drug resistance of the isolates in patient with invasive pneumococcal disease (IPD). Methods: By retrieving the laboratory information system in 18 children′s hospitals from 2012 to 2017, the children with IPD were enrolled. Streptococcus pneumoniae (Spn) must be isolated from the sterile sites (blood, cerebrospinal fluid, hydrothorax and joint effusion etc.). The clinical characteristics, serotype, drug resistance, treatment and prognosis were reviewed and analyzed. According to the telephone follow up results, the patients were divided into death group and recovered group. The index as an independent risk factor of mortality was demonstrated by multivariate logistic regression analysis. Results: There were 1 138 children with IPD, including 684 male and 454 female. The proportion of male to female was 1.5∶1. The age ranged from one day to 16 years. The median age was 1 year 3 month. The majority was under 5 years of age (89.3%, n= 1 016), especially under 2 years of age (61.9%, n=704). In all cases, 88.2% (n=1 004) were community acquired infection. The infections included meningitis (n=446, 39.2%), pneumonia with bacteremia (n=339, 29.8%), and bacteremia without focus (n=232, 20.4%). Underlying diseases were found in 242 cases (21.3%). Co-infections were determined in 62 cases (5.4%) with mycoplasma, 27 cases (2.4%) with adenovirus and 34 cases with influenza virus (3.0%). The penicillin insensitivity (PNSP) rates in meningitis and non-meningitis isolates were 69.5% (276/397) and 35.9% (221/615), respectively. There were 81 strains serotyped, in which 93.8% (76/81) were covered by 13-valent protein-polysaccharide conjugate vaccine (PCV13). In the 965 patients who were followed up by phone call, 156 cases (16.2%) were confirmed dead. The independent risk factors for the death were under 2 years of age (OR=2.143, 95%CI 1.284-3.577, P=0.004), meningitis (OR=3.066, 95%CI 1.852-5.074, P<0.01), underlying disease (OR=4.801, 95%CI 2.953-7.804, P<0.01), septic shock(OR=3.542, 95%CI 1.829-6.859, P<0.01), disseminated intravascular coagulation (DIC) (OR=4.150, 95%CI 1.468-11.733, P=0.007), multiple organ failure (OR=12.693, 95%CI 6.623-24.325, P<0.01) and complications of central nervous system (OR=1.975, 95%CI 1.144-3.410, P=0.015). Conclusions Most children with IPD were under 5 years of age, having underlying diseases and acquired the infection in community. The independent risk factors for death were under two years old, meningitis, underlying diseases and multiple organ failure. The problem of drug resistance was severe. The universal immunization of PCV13 would be effective to prevent IPD in Chinese children.

Objective:To investigate the effects of electroacupuncture (EA) at Neiguan (PC 6) and Baihui (GV 20) by observing the changes of CCAAT/enhancer-binding protein(C/EBP) homologous protein (CHOP) and caspase-12 gene expressions in rats after cerebral ischemia-reperfusion injury (IRI), and explore whether the apoptosis pathway of endoplasmic reticulum stress (ERS) is involved in the protective mechanisms of EA.
Methods:Sixty rats were randomly assigned to five groups (12 in each group): a normal control group (group A), a sham-operation group (group B), an operation group (group C), an Edaravone group (group D) and an EA group (group E). The cerebral IRI rat model was induced by middle cerebral artery occlusion (MCAO) using intraluminal monofilament. 2,3,5-triphenyl tetrazolium chloride (TTC) staining was adopted in the measurement of cerebral infarction volume. Real-time polymerase chain reaction (RT-PCR) was used to determine the mRNA expressions of CHOP and caspase-12.
Results: Compared with group A and group B, the volume of cerebral infarction and mRNA expressions of CHOP and caspase-12 in group C, group D and group E were increased, with statistical significances (P<0.05 orP<0.01); compared with group C, the volume of cerebral infarction and mRNA expressions of CHOP and caspase-12 in group D and group E were decreased significantly (P<0.05 orP<0.01); there were no significant differences between group D and group E in comparing the above items (P>0.05).
Conclusion:EA at Neiguan (PC 6) and Baihui (GV 20) can effectively suppress the volume of cerebral infarction. Furthermore, the underlying mechanism of EA at Neiguan (PC 6) and Baihui (GV 20) is possibly related to the down-regulation of CHOP and caspase-12 mRNA expressions, so as to decrease cell apoptosis.