OBJECTIVE To investigate the current status of quality management of cold chain medicines in direct-to-patient （DTP） pharmacies and propose measures for pre-emptive risk management， providing references for the quality risk management of cold chain medicines. METHODS Based on the requirements of national regulations， a survey was conducted on the quality management of cold chain medicines in DTP pharmacies of J Province from November 2023 to February 2024， focusing on the receipt， storage， distribution， and delivery processes， using questionnaires， telephone interviews， and on-site visits. Common quality management issues in the operation of cold chain medicines were identified， and the causes of these issues were analyzed to propose feasible pre-emptive risk management measures. RESULTS & CONCLUSIONS A total of 122 DTP pharmacies participated in the questionnaire survey， and personnel from 30 DTP pharmacies participated in on-site and telephone interviews. Typical problems were identified in some DTP pharmacies， including insufficient personnel allocation or training， incomplete or inadequate implementation of quality system documentation， inadequate provision or management of cold chain facilities and equipment， and non-compliant storage and distribution of cold chain medicines. These issues posed certain risks to the quality management of cold chain medicines. It is recommended that DTP pharmacies strengthen personnel allocation and training， improve quality system documentation， enhance the provision and management of facilities and equipment， standardize storage and transportation operations， and strengthen supervision and assessment as pre-emptive measures. In addition， all sectors of society should also collaborate in governance from the perspective of ensuring the safety of cold chain drug storage and transportation， in order to mitigate the risk of quality and safety issues during the distribution of cold chain drugs and guarantee the safe and effective use of medications for patients.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder worldwide, causing dementia and affecting millions of individuals. One prominent characteristic in the brains of AD patients is glucose hypometabolism. In the context of galactose metabolism, intracellular glucose levels are heightened. Galactose mutarotase (GALM) plays a crucial role in maintaining normal galactose metabolism by catalyzing the conversion of β-D-galactose into α-D-galactose (α-D-G). The latter is then converted into glucose-6-phosphate, improving glucose metabolism levels. However, the involvement of GALM in AD progression is still unclear. In the present study, we found that the expression of GALM was significantly increased in AD patients and model mice. Genetic knockdown of GALM using adeno-associated virus did not change the expression of amyloid precursor protein (APP) and APP-cleaving enzymes including a disintegrin and metalloprotease 10 (ADAM10), β-site APP-cleaving enzyme 1 (BACE1), and presenilin-1 (PS1). Interestingly, genetic overexpression of GALM reduced APP and Aβ deposition by increasing the maturation of ADAM10, although it did not alter the expression of BACE1 and PS1. Further electrophysiological and behavioral experiments showed that GALM overexpression significantly ameliorated the deficits in hippocampal CA1 long-term potentiation (LTP) and spatial learning and memory in AD model mice. Importantly, direct α-D-G (20 mg/kg, i.p.) also inhibited Aβ deposition by increasing the maturation of ADAM10, thereby improving hippocampal CA1 LTP and spatial learning and memory in AD model mice. Taken together, our results indicate that GALM shifts APP processing towards α-cleavage, preventing Aβ generation by increasing the level of mature ADAM10. These findings indicate that GALM may be a potential therapeutic target for AD, and α-D-G has the potential to be used as a dietary supplement for the prevention and treatment of AD.
Animals ; ADAM10 Protein/metabolism* ; Alzheimer Disease/pathology* ; Amyloid Precursor Protein Secretases/metabolism* ; Disease Models, Animal ; Humans ; Mice ; Amyloid beta-Peptides/metabolism* ; Male ; Mice, Transgenic ; Membrane Proteins/metabolism* ; Cognitive Dysfunction/pathology* ; Mice, Inbred C57BL ; Amyloid beta-Protein Precursor/metabolism* ; Female ; Hippocampus/metabolism* ; Long-Term Potentiation/physiology*

Objective Triple-negative breast cancer(TNBC)poses a significant challenge for treatment efficacy.CD8+T cells,which are pivotal immune cells,can be effectively analyzed for differential gene expression across diverse cell populations owing to rapid advancements in sequencing technology.By leveraging these genes,our objective was to develop a prognostic model that accurately predicts the prognosis of patients with TNBC and their responsiveness to immunotherapy. Methods Sample information and clinical data of TNBC were sourced from The Cancer Genome Atlas and METABRIC databases.In the initial stage,we identified 67 differentially expressed genes associated with immune response in CD8+T cells.Subsequently,we narrowed our focus to three key genes,namely CXCL13,GBP2,and GZMB,which were used to construct a prognostic model.The accuracy of the model was assessed using the validation set data and receiver operating characteristic(ROC)curves.Furthermore,we employed various methods,including Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway,immune infiltration,and correlation analyses with CD274(PD-L1)to explore the model's predictive efficacy in immunotherapeutic responses.Additionally,we investigated the potential underlying biological pathways that contribute to divergent treatment responses. Results We successfully developed a model capable of predicting the prognosis of patients with TNBC.The areas under the curve(AUC)values for the 1-,3-,and 5-year survival predictions were 0.618,0.652,and 0.826,respectively.Employing this risk model,we stratified the samples into high-and low-risk groups.Through KEGG enrichment analysis,we observed that the high-risk group predominantly exhibited enrichment in metabolism-related pathways such as drug and chlorophyll metabolism,whereas the low-risk group demonstrated significant enrichment in cytokine pathways.Furthermore,immune landscape analysis revealed noteworthy variations between(PD-L1)expression and risk scores, Conclusion Our study demonstrates the potential of CXCL13,GBP2,and GZMB as prognostic indicators of clinical outcomes and immunotherapy responses in patients with TNBC.These findings provide valuable insights and novel avenues for developing immunotherapeutic approaches targeting TNBC.

Total hysterectomy is a treatment for cervical intraepithelial neoplasia Ⅲ (CINⅢ), and its recurrence rate is very small. In recent years, with the development of colposcopy and the increase of postoperative follow-up rate, the detection rate of vaginal intraepithelial neoplasia (VAIN) and vaginal cancer after CINⅢ hysterectomy has increased significantly. In recent years, a number of studies have found that persistent human papillomavirus (HPV) infection is the most important factor leading to the recurrence of vaginal stump after CINⅢ level hysterectomy, so eliminating HPV infection can improve the patient's performance. The prognosis of persistent HPV infection is affected by many factors. The author reviewed the factors related to the clearance of HPV after CINⅢ hysterectomy. The purpose of this study is to provide a theoretical basis for improving the prognosis of patients and delaying the recurrence time after CINⅢ hysterectomy.

Objective:To establish an artificial intelligence (AI)-assisted diagnostic system for lung cancer via deep transfer learning.Methods:The researchers collected 519 lung pathologic slides from 2016 to 2019, covering various lung tissues, including normal tissues, adenocarcinoma, squamous cell carcinoma and small cell carcinoma, from the Beijing Chest Hospital, the Capital Medical University. The slides were digitized by scanner, and 316 slides were used as training set and 203 as the internal test set. The researchers labeled all the training slides by pathologists and establish a semantic segmentation model based on DeepLab v3 with ResNet-50 to detect lung cancers at the pixel level. To perform transfer learning, the researchers utilized the gastric cancer detection model to initialize the deep neural network parameters. The lung cancer detection convolutional neural network was further trained by fine-tuning of the labeled data. The deep learning model was tested by 203 slides in the internal test set and 1 081 slides obtained from TCIA database, named as the external test set.Results:The model trained with transfer learning showed substantial accuracy advantage against the one trained from scratch for the internal test set [area under curve (AUC) 0.988 vs. 0.971, Kappa 0.852 vs. 0.832]. For the external test set, the transferred model achieved an AUC of 0.968 and Kappa of 0.828, indicating superior generalization ability. By studying the predictions made by the model, the researchers obtained deeper understandings of the deep learning model.Conclusions:The lung cancer histopathological diagnostic system achieves higher accuracy and superior generalization ability. With the development of histopathological AI, the transfer learning can effectively train diagnosis models and shorten the learning period, and improve the model performance.

Objective:To investigate the relationship between six common cytogenetic abnormalities and bone marrow pathomorphology in multiple myeloma (MM).Methods:Bone marrow biopsy was performed on 151 newly-diagnosed MM patients. Meanwhile, myeloma cells were enriched by CD138 immunomagnetic beads, and then lq+, 13q-, 17p-, t(4;14), t (11;14), t (14;16) and other common genetic abnormalities were detected using interphase fluorescence in situ hybridization (FISH). The relationship between different genetic abnormalities and biopsy morphology was compared.Results:Of the 151 patients, 15 had extramedullary infiltration (9.9%). The rate of cytogenetic abnormalities was 76.2% (115/151), of which 1q+ accounted for 49.7% (75/151), 13q-39.1% (59/151), 17p-8.6% (13/151), t(4;14) 21.2% (32/151), t(11;14) 19.2% (29/151), and t(14;16) 2.0% (3/151). The proliferation patterns of MM plasma cells were nodular (48.3%, 73/151), interstitial (33.8%, 51/151) and diffuse (17.9%, 27/151). The morphology of plasma cells was mainly mature type (58.3%, 88/151), followed by juvenile type (20.5%, 31/151), intermediate type (15.9%, 24/151) and plasmacyte type (5.3%, 8/151). According to the mSMART risk stratification system, the proliferation pattern of myeloma cells in the high-risk group was mainly diffuse type, and the morphology was mainly immature and plasmacyte type. In the middle-risk group, mature type myeloma cells were mainly nodular proliferating. In the low-risk and negative group, mature type myeloma cells were mainly interstitial proliferating. There was no difference in the probability of different proliferation modes of intermediate type plasma cells in each group.Conclusions:The proliferation pattern and morphology of plasma cells in bone marrow biopsy combined with cytogenetic markers can more accurately predict the severity and prognosis of MM.

Objective:To explore the effects of contingency theory-based health education in patients with diabetes mellitus.Methods:Totally 112 diabetic patients admitted into Affiliated Hospital of Shaoxing University from January 2017 to December 2018 were selected by convenient sampling and randomized divided into the control group and the intervention group, with 56 patients in each group. Patients in the control group received routine care, while patients in the observation group received contingency theory-based health education. The health knowledge level, self-care ability, self-efficacy and quality of life of the two groups before and after intervention were compared.Results:The health knowledge level of the intervention group after intervention was higher than that of the control group [ (17.15±2.28) vs. (13.20±2.94) ], and the difference was statistically significant ( P<0.01) . The scores of self-care ability, self-efficacy and quality of life of the intervention group were higher than those of the control group, and the differences were statistically significant ( P<0.01) . Conclusions:The contingency theory-based health education can improve the disease knowledge, self-care ability, self-efficacy and quality of life of diabetic patients, which is worth promoting in clinical practice.

Objective: To investigate the relationship between gastrointestinal disorders (GID) and core symptoms or behavioral problems among the children with autism spectrum disorder (ASD) . Method: Totally 328 children with ASD and 202 normal controls were enrolled in this cross-sectional study from August 2013 to October 2016. The information about the gastrointestinal disorders, behavioral and emotional problems was collected by using questionnaires. Childhood Autism Rating Scale (CARS), Autism Behavior Checklist (ABC) were used to assess the core symptoms of the children with ASD. Neurodevelopmental status was evaluated with Gesell Developmental Scale (GDS). These variables were analyzed by using student's t-test and chi-square test. Result: The prevalence of GID was significantly higher in the children with ASD than in the normally developing children (49.4% (162/328) vs.25.7% (52/202), χ²=29.039, P=0.000), especially the symptoms of constipation (33.2% (109/328) vs. 13.9% (28/202)), diarrhea (9.5%(31/328) vs. 1.5% (3/202)), nausea and vomiting (9.5% (31/328) vs. 3.5% (7/202)), and foul defecation (16.5% (54/328) vs. 5.0% (10/202)) (all P<0.05). Among the ASD children, the prevalence of GID was similar between male and female (46.7% (133/285) vs. 46.5%(20/43), χ²=0.006, P=0.938), as well as among all age groups (χ²=1.907, P=0.862). There was no significant difference in scores of GDS in the ASD children with or without GID (all P>0.05). Compared with ASD children without GID (n=166), the ASD children with GID (n=162) got higher scores in the "Body and Object Use" of ABC scale ( (16.4±9.3) vs. (12.3±6.7) scores, t=2.258, P=0.028), and had more emotional problems (63.6% (103/162) vs. 49.4% (82/166), χ²=6.707, P=0.010). Moreover, the score of behavior problems questionnaire was higher in the ASD children with GID ( (35.3±16.8) vs. (16.1±13.6) scores, t=5.748, P=0.000). Conclusion Children with ASD have higher risk of GID than the normal developing children. While the stereotyped behaviors, problem behaviors and emotional problems are severer in the ASD children with GID. Hence, it is important to provide comprehensive treatment and management for these groups of children.

Objective To establish a zebrafish model of thrombosis induced by three kinds of inducers and observe the anti?thrombotic effect of a Chinese traditional medicine, Guanxinning tablet ( GXN) . Methods The zebrafish models of thrombosis was induced by using 1?5μmol/L phenyl hydrazine, 80μmol/L arachidonic acid and 5 mg/L ponatinib, re?spectively, and were treated with various concentration of GXN, clopidogrel or asprin. The thrombus in the tail vein was observed under microscope, Erythrocytes in the zebrafish heart were stained with o?dianisidine and the erythrocyte staining intensity was assessed with a NIS?Elements DTM image analyzer, and the anti?thrombolic effect of GXN was calculated. Results Venous thrombus was significantly increased and the staining intensities of erythrocytes in the heart were signifi?cantly decreased after induction by phenyl hydrazine, arachidonic acid or Ponatinib ( P <0?001 ) , respectively. At the same time, GXN showed an incresing anti?thrombolic effect in the zebrafish models (P<0?001) in a dose?effect manner, with a IC50 of GXN of 44?32 mg/L,138?5 mg/L and 459?5 mg/L, respectively. Conclusions The zebrafish models of thrombosis are successfully established by phenyl hydrazine, arachidonic acid or Ponatinib, respectively, by different for?mation mechanisms. GXN has been shown to have an anti?thrombosis effect, probably, by multiple target effects.

Objective To explore the efficacy of cold packs combined with ice compress in treatment of pain after erbium fractional photothermal therapy on acne scars. Methods Eighty cases which were confirmed to the criteria were randomized into two groups:treatment group and control group. The treatment group (n=40) treated with cold packs combined with cold icy compress immediately after the surgery for 30~40 mins. The control group (n=40) was given icy compress therapy immediately after the surgery for 30~40 mins. The therapy continued for three days after the surgery on the two groups. The self-feeling symptom and pain relieving time were compared between the two groups. Result The time for pain relief in the wounds and the time for scabbing were both significantly shorter than those in the control group (P<0.01). Conclusion The cold packs combined with ice compress therapy can relieve the pains effectively and it can shorten the recovery time after fractional photothermal therapy.