OBJECTIVE To standardize the main processes and related technical links of the clinical comprehensive evaluation of drugs， and provide guidance and reference for improving the quality of comprehensive evaluation evidence and its transformation and application value. METHODS The construction of Guideline for the Workflow of Clinical Comprehensive Evaluation of Drugs was based on the standard guideline formulation method of the World Health Organization （WHO）， strictly followed the latest definition of guidelines by the Institute of Medicine of the National Academy of Sciences of the United States， and conformed to the six major areas of the Guideline Research and Evaluation Tool Ⅱ. Delphi method was adopted to construct the research questions； research evidence was established by applying the research methods of evidence-based medicine. The evidence quality classification system of the Chinese Evidence-Based Medicine Center was adopted for evidence classification and evaluation. The recommendation strength was determined by the recommendation strength classification standard formulated by the Oxford University Evidence-Based Medicine Center， and the recommendation opinions were formed through the expert consensus method. RESULTS & CONCLUSIONS The Guideline for the Workflow of Clinical Comprehensive Evaluation of Drugs covers 4 major categories of research questions， including topic selection， evaluation implementation， evidence evaluation， and application and transformation of results. The formulation of this guideline has standardized the technical links of the entire process of clinical comprehensive evaluation of drugs， which can effectively guide the high-quality and high-efficient development of this work， enhance the standardized output and transformation application value of evaluation evidence， and provide high-quality evidence support for the scientific decision-making of health and the rationalization of clinical medication.

Objective To investigate the correlation between the characteristics of peritumoral edema and the aggressiveness of breast invasive ductal carcinoma in preoperative magnetic resonance imaging(MRI).Methods A total of 79 patients(79 lesions)who underwent radical mastectomy in the First Affiliated Hospital of Ningbo University from January 2020 to May 2021 and were pathologically diagnosed as invasive ductal carcinoma were included in invasive ductal carcinoma group,and 45 patients(49 lesions)with benign breast lesions were included in benign lesion group during the same period.The difference of peritumoral edema between two groups and the relationship between different pathological features of invasive ductal carcinoma and peritumoral edema were compared.Results The peritumoral edema in benign lesion group was significantly less severe than that in invasive ductal carcinoma group(χ2=25.330,P<0.05).The tumor size of invasive ductal carcinoma group was positively correlated with the degree of peritumoral edema(r=0.381,P<0.05).There were significant differences in molecular type,histological grade,T stage,lymph node metastasis and Ki-67 expression level among patients with different peritumoral edema grades(P<0.05).Ki-67 expression level and the number of lymph node metastasis were positively correlated with the degree of peritumoral edema(r=0.348,0.273,P<0.05).Conclusion The degree of peritumoral edema in MRI correlates with the aggressiveness of breast invasive ductal carcinoma and can be used as one of the tools to evaluate breast carcinoma.

A major impedance to neuronal regeneration after peripheral nerve injury(PNI)is the activation of various programmed cell death mechanisms in the dorsal root ganglion.Ferroptosis is a form of pro-grammed cell death distinguished by imbalance in iron and thiol metabolism,leading to lethal lipid peroxidation.However,the molecular mechanisms of ferroptosis in the context of PNI and nerve regeneration remain unclear.Ferroportin(Fpn),the only known mammalian nonheme iron export protein,plays a pivotal part in inhibiting ferroptosis by maintaining intracellular iron homeostasis.Here,we explored in vitro and in vivo the involvement of Fpn in neuronal ferroptosis.We first delineated that reactive oxygen species at the injury site induces neuronal ferroptosis by increasing intracellular iron via accelerated UBA52-driven ubiquitination and degradation of Fpn,and stimulation of lipid peroxidation.Early administration of the potent arterial vasodilator,hydralazine(HYD),decreases the ubiquitination of Fpn after PNI by binding to UBA52,leading to suppression of neuronal cell death and significant ac-celeration of axon regeneration and motor function recovery.HYD targeting of ferroptosis is a promising strategy for clinical management of PNI.

Objective:To investigate the efficacy of different frequencies of modified electroconvulsive therapy in patients with depressive disorder and its effect on cognitive function and functional near infrared spectroscopy.Methods:The clinical data from 60 patients with depressive disorder, admitted to The Third People's Hospital of Huzhou between December 2022 and July 2023, were retrospectively analyzed. This study was designed as a case-control study. These patients were divided into three treatment groups according to different treatment methods: Group 1 ( n = 20), Group 2 ( n = 20), and Group 3 ( n = 20). All patients underwent conventional antidepressant therapy. Additionally, Group 1 received six sessions of modified electroconvulsive therapy, Group 2 received eight sessions, and Group 3 received ten sessions. The treatment duration for all groups was 4 weeks. Comparisons were made among the three groups for pre- and post-treatment scores on the 24-item Hamilton Depression Rating Scale, 14-item Hamilton Anxiety Rating Scale, Clinical Global Impression Scale, Mini-Mental State Examination, Wisconsin Card Sorting Test, Trail Making Test Part A (TMT-A), Trail Making Test Part B (TMT-B), and Digit Symbol Substitution Test. Furthermore, the incidence of adverse reactions during treatment was calculated, and the Treatment Emergent Symptom Scale was used to assess the occurrence of adverse drug reactions. Moreover, functional Near-Infrared Spectroscopy was used before and after treatment to evaluate the cognitive function of patients under the Verbal Fluency Task. Results:At 1, 2, and 4 weeks of treatment, the 24-item Hamilton Depression Rating Scale, 14-item Hamilton Anxiety Rating Scale, and Clinical Global Impression Scale scores of Group 2 and Group 3 were significantly lower than those of Group 1 ( Finter-group = 32.09, Ftime = 54.27, Finteraction = 7.53, all P < 0.05; Finter-group = 38.14, Ftime = 69.33, Finteraction = 8.59, all P < 0.05; Finter-group = 11.22, Ftime = 28.29, Finteraction = 9.14, all P < 0.05). The Mini-Mental State Examination, Wisconsin Card Sorting Test, and Digit Symbol Substitution Test scores of Group 1 and Group 2 were significantly higher than those of Group 3, while Trail Making Test Part A and Trail Making Test Part B scores of Group 1 and Group 2 were significantly lower than those of Group 3 ( Finter-group = 14.20, Ftime = 44.27, Finteraction = 6.24, all P < 0.05; Finter-group = 18.23, Ftime = 67.15, Finteraction = 8.54, all P < 0.05; Finter-group = 9.30, Ftime = 75.16, Finteraction = 9.41, all P < 0.05; Finter-group = 19.47, Ftime = 85.76, Finteraction = 9.33, all P < 0.05; Finter-group = 22.26, Ftime = 46.37, Finteraction = 6.52, all P < 0.05). There was no significant difference in the incidence of adverse reactions among the three groups ( Finter-group = 3.03, Ftime = 8.36, Finteraction = 1.25, all P > 0.05). After 4 weeks of treatment, the number of Verbal Fluency Task words and oxy-Hb level in Group 2 were significantly higher compared with those in Group 1 and Group 3 ( F = 29.71, 198.57, both P < 0.05). Conclusion:Modified electroconvulsive therapy is highly effective and safe in treating depressive disorders in patients. Eight sessions of modified electroconvulsive therapy administered within 4 weeks have been shown to exhibit better clinical efficacy and lead to greater improvements in cognitive function and functional near-infrared spectroscopy measurements compared with six or ten sessions of treatment.

Background Silicosis is an occupational disease mainly characterized by pulmonary progressive fibrosis induced by the accumulation of free silica (SiO₂) in the lungs due to long-term exposure to SiO₂ dust. It has been shown that neutrophil extracellular traps (NETs) are increased in the lung tissues of silicotic mice after 28 d SiO₂ exposure, but it is unclear how the levels of NETs change throughout entire progression of silicosis in mice. Objective To observe the levels of NETs and pathological changes in the lungs of silicotic mice after different duration of SiO₂ exposure, and to confirm the possible role and significance of NETsin the development of SiO₂-induced pulmonary fibrosis. Methods A total of 28 SPF male C57BL/6J mice were randomly divided into a control group, and a model group, and the model group was subdivided into, a 2 d model group, a 7 d model group, and a 28 d model group, with 7 mice in each group. The mice in the model groups were given intratracheal instillation with 10 mg SiO₂ suspension (50 μL), and the mice in the control group were received same volume of saline. Mice were sacrificed and samples were collected at designed time points. The pathological changes of lung tissues of mice were observed after hematoxylin-eosin (HE) and Van Gieson (VG) staining. Immunofluorescence was used to observe the NETs markers citrullination histone H3 (CitH3) and myeloperoxidase (MPO) in bronchoalveolar lavage fluid (BALF), and the percentage of NETs-positive cells was calculated. PicoGreen fluorescent dye kit was used to detect the content of extracelluar DNA (ex-DNA) in mouse BALF, and the expression levels of fibrosis-related proteins α-smooth muscle actin (α-SMA) and fibronectin (FN) and NETs marker CitH3 in lung tissues of mice were detected by Western blot (WB). Results Compared with the control group, inflammatory cells accumulation, alveolar wall thickening, and collagen deposition were obviously observed in the lungs of the silicosis model groups, and a large number of silicone nodules were recorded in the lung tissues in the 28 d group. Compared with the control group, the expressions of α-SMA and FN in the lung tissue of the 28 d group were significantly increased (P<0.05). The percentages of NETs in BALF increased significantly in the 2 d and the 7 d model group, then decreased in the 28 d model group (P<0.05). Compared with the control group (7.434±0.258) ng·mL⁻¹, the ex-DNA levels in BALF of mice in the 2 d [(35.110±6.331) ng·mL⁻¹], the 7 d [(39.491±6.948) ng·mL⁻¹], and the 28 d [(23.360±4.809) ng·mL⁻¹] model groups were increased (P<0.05), and the increase of ex-DNA in the 2 d and the 7 d model groups were statistically significant (P<0.05). In comparison with the control group, the protein level of CitH3 was significantly increased in the lung tissues of mice in the 7 d model group (P<0.05). Conclusion The content of NETs increases significantly and reaches a peak in the early inflammatory stage of silicosis, and decreases as the disease progresses to the fibrotic stage, suggesting that NETs may play a role in early stage of silicosis.

Objective:We aimed to develop a novel visualized model based on nomogram to predict postoperative overall survival.Methods:This was a multicenter, retrospective, observational cohort study, including participants with histologically confirmed gastric and colorectal cancer who underwent radical surgery from 11 medical centers in China from August 1, 2015 to June 30, 2018. Baseline characteristics, histopathological data and nutritional status, as assessed using Nutrition Risk Screening 2002 (NRS 2002) score and the scored Patient-Generated Subjective Global Assessment, were collected. The least absolute shrinkage and selection operator regression and Cox regression were used to identify variables to be included in the predictive model. Internal and external validations were performed.Results:There were 681 and 127 patients in the training and validation cohorts, respectively. A total of 188 deaths were observed over a median follow-up period of 59 (range: 58 to 60) months. Two independent predictors of NRS 2002 and Tumor-Node-Metastasis (TNM) stage were identified and incorporated into the prediction nomogram model together with the factor of age. The model's concordance index for 1-, 3- and 5-year overall survival was 0.696, 0.724, and 0.738 in the training cohort and 0.801, 0.812, and 0.793 in the validation cohort, respectively.Conclusions:In this study, a new nomogram prediction model based on NRS 2002 score was developed and validated for predicting the overall postoperative survival of patients with gastric colorectal cancer. This model has good differentiation, calibration and clinical practicability in predicting the long-term survival rate of patients with gastrointestinal cancer after radical surgery.

Mastitis is one of the most widespread infectious diseases that adversely affects the profitability of the dairy industry worldwide. Accurate diagnosis and identification of pathogens early to cull infected animals and minimize the spread of infection in herds is critical for improving treatment effects and dairy farm welfare. The major pathogens causing mastitis and pathogenesis are assessed first. The most recent and advanced strategies for detecting mastitis, including genomics and proteomics approaches, are then evaluated .Finally, the advantages and disadvantages of each technique, potential research directions, and future perspectives are reported. This review provides a theoretical basis to help veterinarians select the most sensitive, specific, and cost-effective approach for detecting bovine mastitis early.

OBJECTIVE To explore the pharmaceutical service model in multidisciplinary diagnosis and treatment （MDT） of rare diseases in children. METHODS Clinical pharmacists of West China Second University Hospital （hereinafter referred to as “our hospital”） participated in the process of MDT of children’s rare diseases. Clinical pharmacists took part in the entire diagnosis and treatment process of children and established the MDT pharmaceutical service model of children’s rare diseases by formulating drug treatment plans based on evidence-based practice， improving the accessibility of drugs， pharmaceutical monitoring and drug treatment management. RESULTS From January 2021 to April 2022， clinical pharmacists of our hospital had participated in a total of 39 cases of rare diseases MDT in children， including 21 hospitalized children with rare diseases and 18 outpatient com children with rare diseases， involving a total of 23 rare diseases. Clinical pharmacists completed 45 pharmaceutical zhanglingli@scu.edu.cn rounds and 26 pharmaceutical consultations for rare diseases inpatients， 25 outpatients’ MDT and 5 pharmaceutical outpatient service for outpatients with rare diseases， 38 medication educations for inpatients and outpatients with rare diseases and 25 follow-up services for out-of-hospital patients. There were 24 cases （61.54%） of off-label drug use， involving 13 rare diseases and 16 therapeutic drugs， among which off-label drug use registration of 11 drugs had been completed or was in progress. The temporary purchase evaluations of 3 drugs had been completed； 268 cases of medical insurance drug and high-value drug prescription had been reviewed. CONCLUSIONS Our hospital have primarily established a loop pharmaceutical service model of MDT for children with rare diseases， which covers inpatients and outpatients. The model improves the availability and standardization of clinical application of therapeutic drugs， and diagnosis and treatment level for children with rare diseases in our hospital.

Proto-Oncogene Proteins c-akt/metabolism* ; Butyrates ; Ligands ; Glucose ; Receptors, G-Protein-Coupled/metabolism* ; Glycogen Synthase Kinases/metabolism* ; Glycogen Synthase Kinase 3 beta ; Phosphorylation

ObjectiveTo observe the clinical effect of Yiqi Liangxue Shengji Formula （益气凉血生肌方， YLSF） on recurrence of angina pectoris and quality of life at eight weeks after perecutaneous coronary intervention （PCI）. MethodsEighty-two coronary artery disease （CAD） patients with qi deficiency and blood stasis and binding of stasis and heat syndrome who had underwent PCI were randomly divided into two groups with 41 patients each in the treatment group and the control group. Based on conventional western medicine after PCI， patients in the treatment group orally took YLSF granules while those in the control group were administered with placebo， one dose daily for 8 weeks. The recurrence rate of angina pectoris and readmission rate within eight weeks after PCI were recorded. Before and after treatment， total traditional Chinese medicine （TCM） syndrome score， Seattle Angina Questionnaire （SAQ） scores （physical limitation， angina stability， angina frequency， treatment satisfaction and disease perception）， and the SF-36 scores for quality of life （physical and mental health） were evaluated. The adverse reactions during medication in both groups were recorded. ResultsWithin eight weeks after PCI， the recurrence rate of angina pectoris in the treatment group （4/41， 9.76%） was significantly lower than that in the control group （11/41， 26.83%， P＜0.05）. The readmission rate in the treatment group was 2.44% （1/41）， while that in the control group was 12.20% （5/41）， with no significantly statistical difference （P＞0.05）. After treatment， total TCM syndrome score significantly decreased in both groups， while in terms of quality of life， the SAQ scores on domains of angina stability， angina frequency and disease perception as well as SF-36 total scores， physical health and mental health scores significantly increased （P＜0.05 or P＜0.01）. Compared between the two groups， total TCM syndrome score was significantly lower in the treatment group than the control group （P＜0.01）， while no significant differences were found in SAQ scores and SF-36 total， physical and mental health scores （P＞0.05）. No adverse reactions occurred in both groups during the treatment period. ConclusionYLSF can reduce the recurrence rate of angina pectoris within eight weeks after PCI for coronary artery disease， and can improve the TCM syndrome score， and have sound safety， with comparable effect to that of placebo in improving postoperative short-term quality of life.