Pancreatic cancer is currently recognized as one of the most malignant solid tumors， with a 5-year survival rate of 13% over a long period of time， and 80% of the patients have lost the opportunity for surgery at the time of confirmed diagnosis. In addition， the efficacy of conventional radiochemotherapy and targeted therapy is limited by high tumor heterogeneity and the complex immunosuppressive microenvironment. In recent years， mRNA vaccines have become a new focus of tumor immunotherapy due to their unique technical advantages. Based on non-integrating mRNA templates， mRNA vaccines enable precise encoding of tumor neoantigens， which are efficiently expressed in the host and can induce multifaceted immune responses. As for pancreatic cancer， current studies mainly focus on the development and optimization of tumor-associated antigen vaccines and tumor-specific antigen vaccines， as well as next-generation sequencing-guided neoantigen epitope optimization， innovative targeted delivery systems， and artificial intelligence-powered predictive models for immune response， thereby promoting the application of mRNA vaccines in the precise treatment of pancreatic cancer. Further studies should make breakthroughs in the targeted blockade of critical immunosuppressive molecules within the tumor microenvironment， the precise identification of tumor-specific antigenic epitopes， and the development of highly efficient vaccines， so as to bring new hopes for patients with pancreatic cancer.

The writing of pharmacist-managed clinics documents （hereinafter referred to as “outpatient medication record”） is a necessary part of pharmacist-managed clinics service. Outpatient medication record is an important carrier to reflect the quality of pharmacist-managed clinics service. The Chinese Hospital Association Pharmaceutical Specialized Committee was entrusted by the Pharmaceutical Administration Department of the National Health Commission to lead the formulation of the Guidelines for the Pharmacist-managed Clinics Service and Document Writing and Usage （Reference） （hereinafter referred to as Guidelines） according to the compilation method of group standards and the technical route of “documentation combing→framework establishment→draft writing→opinion collection→Guidelines formation”. The Guidelines standardizes the basic requirements of pharmacist-managed clinics record management and the basic content of record， and provides a general template and two specialized templates including pregnant and lactating pharmacist-managed clinics record template and cough and asthma pharmacist-managed clinics record template， which provides a reference for medical institutions to write pharmacist-managed clinics record. This paper introduces the formulation process of Guidelines and analyzes the key contents of Guidelines， which is helpful for the application practice of Guidelines and further improves the quality of pharmacist-managed clinics work.

OBJECTIVE To analyze clinical switching patterns and reasons between bevacizumab biosimilar and originator drugs. METHODS The data were collected from 1 175 cancer patients treated with bevacizumab at Ruijin Hospital， Shanghai Jiao Tong University School of Medicine from January 1， 2018， to December 31， 2023. The patients were divided into originator group （n＝250） and biosimilar group （n＝925）. The switching rate， switching type and reasons of the two groups were compared. RESULTS There were no statistically significant differences in the switching rate， switching types， and the number of switches between the two groups （P＞0.05）. Single， one-way switches were the switching type in both groups. The proportion of patients in the biosimilar group who switched due to adverse events was significantly higher than originator group， while the proportion of patients who switched due to treatment costs was significantly lower than originator group （P＜0.05）. There were no statistically significant differences in the proportions of patients who switched due to efficacy and drug accessibility between the two groups （P＞0.05）. CONCLUSIONS The switching between bevacizumab biosimilar and the originator drugs mainly involves single， one- way switches. Treatment costs and drug accessibility are the main factors for the switches among users of originator drugs， while drug accessibility and adverse events are the main factors for the switches among users of biosimilar.

The prefrontal cortex and hippocampus may support sequential working memory beyond episodic memory and spatial navigation. This stereoelectroencephalography (SEEG) study investigated how the dorsolateral prefrontal cortex (DLPFC) interacts with the hippocampus in the online processing of sequential information. Twenty patients with epilepsy (eight women, age 27.6 ± 8.2 years) completed a line ordering task with SEEG recordings over the DLPFC and the hippocampus. Participants showed longer thinking times and more recall errors when asked to arrange random lines clockwise (random trials) than to maintain ordered lines (ordered trials) before recalling the orientation of a particular line. First, the ordering-related increase in thinking time and recall error was associated with a transient theta power increase in the hippocampus and a sustained theta power increase in the DLPFC (3-10 Hz). In particular, the hippocampal theta power increase correlated with the memory precision of line orientation. Second, theta phase coherences between the DLPFC and hippocampus were enhanced for ordering, especially for more precisely memorized lines. Third, the theta band DLPFC → hippocampus influence was selectively enhanced for ordering, especially for more precisely memorized lines. This study suggests that theta oscillations may support DLPFC-hippocampal interactions in the online processing of sequential information.
Adult ; Female ; Humans ; Young Adult ; Epilepsy ; Hippocampus ; Memory, Short-Term ; Mental Recall ; Prefrontal Cortex ; Theta Rhythm ; Male

Using the liquid chromatography-tandem mass spectrometry (LC-MS/MS) to determine the plasma level of Lyso-GL3 in patients with Fabry disease and to analyze the clinical application of the method.

Objective To compare the effect of palliative mitral valve surgeries and medication therapies for secondary non-ischemic mitral regurgitation. Methods The clinical data of patients with non-ischemic functional mitral regurgitation treated in our hospital between 2009 and 2019 were retrospectively analyzed. Patients with a left ventricular ejection fraction (LVEF)＜40% underwent a dobutamine stress test, and a positive result was determined when the LVEF improved by more than 15% compared to the baseline value. Positive patients were divided into a surgery group and a medication group. The surgery group underwent surgical mitral valve repair or replacement, while the medication group received simple medication treatment. Follow-up on survival and cardiac function status through outpatient or telephone visits every six months after surgery, and patients underwent cardiac ultrasound examination one year after surgery. The main research endpoint was a composite endpoint of all-cause death, heart failure readmission, and heart transplantation, and the differences in cardiac function and cardiac ultrasound parameters between the two groups were compared. Results Ultimately 41 patients were collected, including 28 males and 13 females with an average age of 55.5±11.1 years. Twenty-five patients were in the surgery group and sixteen patients in the medication group. The median follow-up time was 16 months, ranging 1-96 months. The occurrence of all-cause death in the surgery group was lower than that in the medication group (HR=0.124, 95%CI 0.024-0.641, P=0.034). The difference between the two groups was not statistically significant in the composite endpoint (HR=0.499, 95%CI 0.523-1.631, P=0.229). The New York Heart Association (NYHA) grade of the surgery group was better (NYHA Ⅰ-Ⅱ accounted for 68.0% in the surgury group and 18.8% in the medication group, P<0.01) as well as the grade of mitral valve regurgitation (87.5% of the patients in the medication group had moderate or above regurgitation at follow-up, while all the patients in the surgery group had moderate below regurgitation, P<0.01). There was no statistical difference in preoperative and follow-up changes in echocardiograph parameters between the two groups (P＞0.05). Conclusion For non-ischemic functional mitral regurgitation, if the cardiac systolic function is well reserved, mitral valve surgery can improve survival and quality of life compare to simple medication therapy.

【Objective】 To study the relationship between ABO subtype, para-Bombay blood group and genotype, so as to explore the possible molecular mechanism of these two blood groups, and provide accurate genetic detection targets and theoretical basis for the accurate identification of ABO blood group. 【Methods】 First, the serology of 24 200 patients with blood type identification in the Ruijin Hospital from February to December in 2022 were analyzed, as well as 10 ambiguous ABO samples from other hospitals(3 were suspected ABO subtype and 7 were suspected para-Bombay blood group). Then ABO subtypes and para-Bombay blood groups were directly sequenced or post-clonal sequencing was performed to analyze ABO, FUT1 and FUT2 gene sequences. 【Results】 Among the 24 200 patients underwent blood type identification, 7 cases of ABO subtypes were detected. Among the 10 ambiguous samples sent by other hospitals, 2 of ABO subtypes, 1 of normal type A, and 7 of para-Bombay blood type were detected. In total, we identified blood types as follows: 1) 9 ABO subtypes: Ael(AEL.02/O.01.02), AelB(AEL.05/B.01), three of B3(2 of B3.03/O.01.01, 1 of B3.03/O.01.02), B(A)(BA.02/O.01.01), ABweak(A1.02/BW.07), Bweak(BW.31 /O.01.02), A2Bweak(A2.05 /BW.31); 2) 7 para-Bombay blood group: ABm^h (FUT1^*01N.13/FUT1^*01N.13), 4 of Am^h (3 of FUT1^*01N.06/FUT1^*01N.13, 1 of FUT1^*01N.13/FUT1^*01N.13); two of Bm^h (FUT1^*01N.06 /FUT1^*01N.06, FUT1^*01N.06/FUT1^*01N.13), all of FUT2 of the 7 cases were FUT2^*01/FUT2^*01. 【Conclusion】 Clinical ABO blood group variant samples need to be identified in combination with serological and molecular biology to improve the accuracy of identification, thus providing a reference for safe blood transfusion, organ transplantation, and the prediction and prevention of fetal-maternal immune hemolytic disease.

Objective:To evaluate the relationship between inositol-requiring enzyme 1α-X box-binding protein 1 (IRE1α-XBP1) signaling pathway in endoplasmic reticulum and neutrophil extracellular traps during endotoxin-induced acute lung injury (ALI) in mice.Methods:Forty-eight SPF healthy male C57BL/6 mice, aged 6-8 weeks, weighing 25-30 g, were divided into 4 groups ( n=12 each) using a random number table method: control group (C group), STF-083010 group (ST group), lipopolysaccharide (LPS)-induced ALI group (ALI group) and LPS-induced ALI + STF-083010 group (ALI+ ST group). The ALI model was established by inhaling aerosolized LPS in ALI group and ALI+ ST group. The equal volume of aerosolized normal saline was inhaled in C and ST groups. IRE1α inhibitor STF-083010 50 mg/kg was intraperitoneally injected at 1 h before developing the model in ST and ALI+ ST groups, and the equal volume of normal saline was intraperitoneally injected in the other two groups. The mice were sacrificed after anesthesia at 24 h after developing the model. Bronchoalveolar lavage fluid (BALF) and lung tissues were collected for determination of the pathological changes (by light microscopy) which were scored, wet/dry lung weight (W/D) ratio, concentrations of interleukin-1beta (IL-1β), IL-18 and myeloperoxidase (MPO) in the BALF supernatant, and expression of phosphorylated IRE1α(p-IRE1α), XBP1s and citrullinated histone H3 (Cit H3) in lung tissues (using Western blot). Results:Compared to group C, the lung injury scores and W/D ratio were significantly increased at 24 h after developing the model, the concentrations of IL-1β, IL-18 and MPO in BALF were increased, and the expression of p-IRE1α, XBP1s and Cit H3 in lung tissues was up-regulated in ALI and ALI+ ST groups. Compared to group L, the lung injury scores and W/D ratio were significantly decreased at 24 h after developing the model, the concentrations of IL-1β, IL-18 and MPO in BALF were decreased, and the expression of p-IRE1α, XBP1s and Cit H3 in lung tissues was down-regulated in group ALT+ ST ( P<0.05). Conclusions:The IRE1α-XBP1 signaling pathway in endoplasmic reticulum is involved in endotoxin-induced ALI by up-regulating the expression of neutrophil extracellular traps in mice.

Objective: This study aimed to determine whether surgery followed by adjuvant chemoradiotherapy has superior survival outcomes for node-positive patients with T1b1-T2a1 stage cervical cancer compared with those who undergo chemoradiation. Methods: We investigated the Surveillance, Epidemiology, and End Results database for 12,701 patients diagnosed between 2000 and 2018. Patients were stratified according to different T stages and different treatment strategies. Surgery included radical hysterectomy (RH) or total hysterectomy (TH). Radiotherapy (RT) included adjuvant chemoradiation or chemoradiation alone. Cox analyses were performed to select the clinically important factors of survival outcomes. Survival analysis was used to compare those who received different treatment methods. Results: A total of 12,701 International Federation of Gynecology and Obstetrics 2018 stage IIIC cervical cancer patients were identified. The risk of overall survival (OS) was significantly different between patients who received and did not receive chemoradiotherapy in the T categories. In the propensity-score matched dataset, early-T stage (T1b1 and T1b2) and node-positive patients in the “RH+RT” and “TH+RT” groups had better disease-specific survival (DSS) than those in the RT group. No difference in DSS was observed between the “surgery following RT” group and the RT group in locally advanced stage (T1b3 and T2a1, node positive) patients. Regarding T1b1-T2a1 node-positive patients, the RH+RT group had a similar survival outcome to that in the TH+RT group. Conclusion We showed that surgery following RT benefits early-T stage (T1b1 and T1b2) cervical cancer patients with lymph node metastasis. For locally advanced stages (T1b3 and T2a1), surgery and RT had similar survival outcomes.

Purpose: To determine the non-contrast computer tomography imaging features of pyonephrosis and evaluate the predictive value of Hounsfield units (HUs) in different hydronephrotic region slices. Materials and Methods: We retrospectively reviewed data from patients with hydronephrosis who had renal-ureteral calculi. All patients were categorized into pyonephrosis and simple hydronephrosis groups. Baseline characteristics, the mean HU values in the maximal hydronephrotic region (uHU) slice, and the range of uHU in different slices (△uHU) were compared between the two groups. Univariate and multivariate analyses were performed to identify risk factors for pyonephrosis. Results: Among the 181 patients enrolled in the current study, 71 patients (39.2%) were diagnosed with pyonephrosis. The mean dilated pelvis surface areas were comparable between patients with pyonephrosis and simple hydronephrosis (822.61 ㎟ vs.877.23 ㎟ , p=0.722). Collecting system debris (p=0.022), a higher uHU (p=0.038), and a higher △uHU (p<0.001) were identified as independent risk factors for pyonephrosis based on multivariate analysis. The △uHU sensitivity and specificity were 88.7% and 86.4%, respectively, at a cutoff value of 6.56 (p<0.001), whereas the sensitivity and specificity for detecting pyonephrosis at a uHU cutoff value of 7.96 was 50.7% and 70.9%, respectively (p=0.003). Conclusions Non-contrast computer tomography was shown to accurately distinguish simple hydronephrosis from pyonephrosis in patients with obstructive uropathy. Evaluation of the △uHU in different slices may be more reliable than the uHU acquired from a single slice in predicting pyonephrosis.