Diabetes is a very complex endocrine disease whose common feature is the increase in blood glucose concentration. Persistent hyperglycemia can lead to blindness, kidney and heart disease, neurodegeneration, and many other serious complications that have a significant impact on human health and quality of life. The number of people with diabetes is increasing yearly. The global diabetes prevalence in 20-79 year olds in 2021 was estimated to be 10.5% (536.6 million), and it will rise to 12.2% (783.2 million) in 2045. The main modes of intervention for diabetes include medication, dietary management, and exercise conditioning. Medication is the mainstay of treatment. Marketed diabetes drugs such as metformin and insulin, as well as GLP-1 receptor agonists, are effective in controlling blood sugar levels to some extent, but the preventive and therapeutic effects are still unsatisfactory. Peptide drugs have many advantages such as low toxicity, high target specificity, and good biocompatibility, which opens up new avenues for the treatment of diabetes and other diseases. Currently, insulin and its analogs are by far the main life-saving drugs in clinical diabetes treatment, enabling effective control of blood glucose levels, but the risk of hypoglycemia is relatively high and treatment is limited by the route of delivery. New and oral anti-diabetic drugs have always been a market demand and research hotspot. Inhibitor cystine knot (ICK) peptides are a class of multifunctional cyclic peptides. In structure, they contain three conserved disulfide bonds (C3-C20, C7-C22, and C15-C32) form a compact “knot” structure, which can resist degradation of digestive protease. Recent studies have shown that ICK peptides derived from legume, such as PA1b, Aglycin, Vglycin, Iglycin, Dglycin, and aM₁, exhibit excellent regulatory activities on glucose and lipid metabolism at the cellular and animal levels. Mechanistically, ICK peptides promote glucose utilization by muscle and liver through activation of IR/AKT signaling pathway, which also improves insulin resistance. They can repair the damaged pancrease through activation of PI3K/AKT/Erk signaling pathway, thus lowering blood glucose. The biostability and hypoglycemic efficacy of the ICK peptides meet the requirements for commercialization of oral drugs, and in theory, they can be developed into natural oral anti-diabetes peptide drugs. In this review, the structural properties, activity and mechanism of ICK pattern peptides in regulating glucose and lipid metabolism were summaried, which provided a reference for the development of new oral peptides for diabetes.

A Clinical pharmacist was fully involved in the anticoagulation drug treatment management process of a 104-year-old patient with a large area of cerebral infarction combined with chronic kidney disease stage Ⅴ and secondary deep vein thrombosis.After the patient was diagnosed with deep vein thrombosis,the clinical pharmacist comprehensively analyzed the patient's super-advanced age,history of atrial fibrillation,large area of cerebral infarction,extremely poor kidney function,deep vein thrombosis,and high bleeding risk indicated by the HAS-BLED score.They worked with the clinical doctor to develop an individualized anticoagulation treatment strategy for the patient.At the beginning of the treatment,warfarin was given to the patient at a daily dose of 1.25 mg,and the patient's coagulation indicators and kidney function were dynamically rechecked.The patient's blood creatinine level did not show significant changes throughout the anticoagulation treatment process.On the 8th day of medication,the patient's INR was 2.47,and the clinical pharmacist suggested adjusting the Warfarin to an alternate-day dose of 1.25 mg and 0.625 mg.Subsequently,the patient's INR was 2.41,and the condition improved,leading to discharge.Throughout the anticoagulation drug management process,the clinical pharmacist participated in the clinical decision-making for anticoagulant drug selection,provided professional medication guidance,and pharmacological monitoring to ensure the safe clinical use of drugs for special populations.

The whole developing history of the in-flight bladder relief device for US fighter pilots from the first generation to the third generation was introduced.The optimized design of the third-generation product was described in terms of male use and female use.It's pointed out the US Air Force developed the in-flight bladder relief device with the mode of integration and innovation,the idea closely following the troops'needs and the key technology upgrading thought introducing the newest achievements,and references were provided for the technical improvement of this type of device for the PLA.[Chinese Medical Equipment Journal,2024,45(6):71-76]

Umbilical cord mesenchymal stem cells (UC-MSCs) have been widely used in regenerative medicine, but there is limited research on the stability of UC-MSCs formulation during production. This study aims to assess the stability of the cell stock solution and intermediate product throughout the production process, as well as the final product following reconstitution, in order to offer guidance for the manufacturing process and serve as a reference for formulation reconstitution methods. Three batches of cell formulation were produced and stored under low temperature (2-8 ℃) and room temperature (20-26 ℃) during cell stock solution and intermediate product stages. The storage time intervals for cell stock solution were 0, 2, 4, and 6 h, while for intermediate products, the intervals were 0, 1, 2, and 3 h. The evaluation items included visual inspection, viable cell concentration, cell viability, cell surface markers, lymphocyte proliferation inhibition rate, and sterility. Additionally, dilution and culture stability studies were performed after reconstitution of the cell product. The reconstitution diluents included 0.9% sodium chloride injection, 0.9% sodium chloride injection + 1% human serum albumin, and 0.9% sodium chloride injection + 2% human serum albumin, with dilution ratios of 10-fold and 40-fold. The storage time intervals after dilution were 0, 1, 2, 3, and 4 h. The reconstitution culture media included DMEM medium, DMEM + 2% platelet lysate, 0.9% sodium chloride injection, and 0.9% sodium chloride injection + 1% human serum albumin, and the culture duration was 24 h. The evaluation items were viable cell concentration and cell viability. The results showed that the cell stock solution remained stable for up to 6 h under both low temperature (2-8 ℃) and room temperature (20-26 ℃) conditions, while the intermediate product remained stable for up to 3 h under the same conditions. After formulation reconstitution, using sodium chloride injection diluted with 1% or 2% human serum albumin maintained a viability of over 80% within 4 h. It was observed that different dilution factors had an impact on cell viability. After formulation reconstitution, cultivation in medium with 2% platelet lysate resulted in a cell viability of over 80% after 24 h. In conclusion, the stability of cell stock solution within 6 h and intermediate product within 3 h meets the requirements. The addition of 1% or 2% human serum albumin in the reconstitution diluent can better protect the post-reconstitution cell viability.

Non-small cell lung cancer is one of the cancers with the highest incidence and mortality rate in the world, and precise prognostic models can guide clinical treatment plans. With the continuous upgrading of computer technology, deep learning as a breakthrough technology of artificial intelligence has shown good performance and great potential in the application of non-small cell lung cancer prognosis model. The research on the application of deep learning in survival and recurrence prediction, efficacy prediction, distant metastasis prediction, and complication prediction of non-small cell lung cancer has made some progress, and it shows a trend of multi-omics and multi-modal joint, but there are still shortcomings, which should be further explored in the future to strengthen model verification and solve practical problems in clinical practice.

Objective To investigate the distribution of traditional Chinese medicine(TCM)syndromes in patients with type 2 diabetic retinopathy(T2DR)and to explore the correlation of TCM syndromes with serum inflammatory factors and adiponectin(APN)levels,so as to provide evidence for TCM syndrome differentiation of T2DR.Methods A cross-sectional case-control study was conducted in 42 patients(involving 84 eyes)diagnosed as T2DR in the Department of Ophthalmology,Ganzhou People's Hospital from September 2022 to March 2023.The correlation between fundus fluorescein angiography(FFA)staging and TCM syndrome differentiation in patients with T2DR was explored.The relationship between TCM syndrome types and serum levels of inflammatory factors and APN,as well as the differences in serum inflammatory factors and APN levels of the patients with various FFA stages were analyzed.The correlation between each variable and TCM syndrome types in patients with T2DR was investigated.Results(1)Among the 42 patients with T2DR,27 cases were male and 15 cases were female,and their age averaged(54.0±12.0)years old.Among them,14 cases(33.3％)were differentiated as liver-kidney deficiency with malnutrition of eye collateral syndrome,15 cases(35.7％)were differentiated as yin-essence deficiency with internal dry-heat syndrome,9 cases(21.4％)were differentiated as qi-yin deficiency with collateral stasis and obstruction syndrome,4 cases(9.5％)were differentiated as yin-yang deficiency with blood stasis and phlegm coagulation syndrome,and none case(0.0％)was differentiated as spleen dysfunction and water-damp obstruction syndrome.(2)FFA staging showed that FFA staging ≥ 4[i.e.,having proliferative diabetic retinopathy(PDR)]was found in 78.6％(11/14)of the patients with liver-kidney deficiency with malnutrition of eye collaterals syndrome,73.3％(11/15)of the patients with yin-essence deficiency with internal dry-heat syndrome,100％(9/9)of the patients with qi-yin deficiency with collateral stasis and obstruction syndrome,and 100％(4/4)of the patients with yin-yang deficiency with blood stasis and phlegm coagulation syndrome.But the intergroup comparison showed no significant differences among various syndrome types(P=0.272).(3)Among the 42 patients with T2DR,35 patients(83.3％)had higher level of tumor necrosis factor-α(TNF-α),28 patients(68.3％)had higher level of C-reactive protein(CRP)and 38 patients(90.5％)had higher level of glycosylated hemoglobin(HbA1c)than the normal.However,there was no significant difference in the levels of serum inflammatory factors of TNF-α,CRP,interleukin-6(IL-6)and vascular endothelial growth factor(VEGF),APN and HbA1c among the patients with different FFA stages(P＞0.05),neither did the difference in serum APN,TNF-α,CRP,IL-6 and VEGF levels among the patients with different TCM syndrome types(P＞0.05).(4)The correlation analysis showed that the patients with yin-yang deficiency with blood stasis and phlegm coagulation syndrome had a shorter course of eye diseases than the patients with liver-kidney deficiency with malnutrition of eye collaterals syndrome(r=-0.467,P=0.051),had higher CRP level than the patients with yin-essence deficiency with internal dry-heat syndrome(r=0.592,P=0.010),and had higher CRP level(r=0.668,P=0.013)and a longer course of diabetes(r=0.629,P=0.021)than the patients with qi-yin deficiency with collateral stasis and obstruction syndrome.Conclusion Increased serum TNF-α and CRP expressions are presented in the patients with T2DR.Liver-kidney deficiency with malnutrition of eye collaterals syndrome and yin-essence deficiency with internal dry-heat syndrome are the common syndromes in T2DR.Yin-yang deficiency with blood stasis and phlegm coagulation syndrome is closely correlated with CRP level,and the patients with yin-yang deficiency with blood stasis and phlegm coagulation syndrome have a longer course of diabetes.

Background/Aims: The histological characteristics and natural history of precirrhotic primary biliary cholangitis (PBC) with portal hypertension (PH) are unclear. Our aim was to clarify the prevalence, risk factors, and histological characteristics of precirrhotic PBC patients with PH. Methods: This retrospective study compared the clinical features, histological characteristics, and response to ursodeoxycholic acid (UDCA) between the PH and non-PH groups of precirrhotic PBC patients. Results: Out of 165 precirrhotic PBC patients, 40 (24.2%) also had PH. According to histological stage 1, 2 and 3 disease, 5.3% (1/19), 17.3% (17/98), and 45.8% (22/48) of patients also had PH, respectively. Precirrhotic PBC with PH was significantly positively correlated with bile duct loss, degree of cytokeratin 7 positivity, and degree of fibrosis in the portal area, but significantly negatively correlated with lymphoid follicular aggregation. Compared to the non-PH group, patients in the PH group showed a higher prevalence of obliterative portal venopathy, incomplete septal fibrosis, portal tract abnormalities and non-zonal sinusoidal dilatation (p<0.05). In addition, patients with PH were more likely to present with symptoms of jaundice, ascites, epigastric discomfort, a poorer response to UDCA, and more decompensation events (p<0.05). High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values were risk factors for precirrhotic PBC with PH. Conclusions Approximately 24.2% of precirrhotic PBC patients have PH, which is histologically related to the injury of bile ducts. High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values are associated with increased risk of precirrhotic PBC with PH.

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34⁺⁰ weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.
Infant ; Infant, Newborn ; Humans ; Birth Weight ; Intensive Care Units, Neonatal ; Retrospective Studies ; Tertiary Care Centers ; Infant, Extremely Low Birth Weight ; Gestational Age ; Infant, Extremely Premature ; Sepsis/epidemiology* ; Retinopathy of Prematurity/epidemiology* ; Bronchopulmonary Dysplasia/epidemiology*

AIM: To explore the effects of anti-vascular endothelial growth factor(VEGF)agents(Conbercept)before pars plana vitrectomy(PPV)on inflammatory cytokine levels of patients with proliferative diabetic retinopathy(PDR).METHODS: A total of 49 patients(49 eyes)who diagnosed with PDR at the First Affiliated Hospital with Nanjing Medical University from June 2017 to January 2018 were recruited and randomly divided into two groups. A total of 25 cases(25 eyes)who did not receive intravitreal injection before PPV were included in no-intravitreal injection of Conbercept(IVC)group, and 24 cases(24 eyes)who received IVC 5～7d before PPV were included in IVC group. The vitreous samples were collected from all the patients at the start of PPV. Levels of VEGF-A, monocyte chemotactic protein-1(MCP-1)and inflammatory cytokines in the vitreous humor were measured using Luminex technology.RESULTS: Compared with the no-IVC group, the level of VEGF-A decreased significantly(P<0.001), the concentration of IL-6(P=0.004), IL-8(P=0.002), IL-18(P=0.04)and TNF-α(P=0.03)increased remarkably in the IVC group. The other inflammatory cytokines in the vitreous humor showed no significant difference between the IVC and no-IVC groups.CONCLUSION: IVC before PPV can effectively decrease the concentration of VEGF-A, but had limited influence on the level of inflammatory cytokines in the vitreous humor of patients with PDR.

objectiveTo explore the specific molecular mechanism of neuronal apoptosis induced by ATM inactivation. MethodsCGNs matured 7 days in vitro were cultured 8 h with 25 K， 5 K or 25 K medium containing ATM-specific inhibitors （Ku55933， 10 µmol/L； Ku60019， 15 µmol/L） for Hoechst stain and apoptosis analysis， or cultured for different lengths of time （2， 4， 8 h） to detect the protein expression levels of ATM， caspase-3 and cleaved caspase-3 by Western blotting. ATM and GADD45α specific siRNA was transfected into C6 cells and CGNs， and its interference efficiency was verified by q-PCR and Western blotting. CGNs matured for 5 days in vitro were transfected with ATM specific siRNA and pCMV-EGFP by calcium phosphate for 48 h， Hoechst staining and apoptosis analysis were performed. CGNs matured for 7 days in vitro were treated with 25 K medium containing ATM specific inhibitors for 8 h， transcriptome sequencing， differential expression gene identification and pathway enrichment analysis were performed. CGNs matured for 5 days in vitro were co-transfected with GADD45α specific siRNA and pCMV-EGFP by calcium phosphate for 48 h， then treated with 5 K or 25 K medium containing 15 µmol/L Ku6 for 8 h. Hoechst staining and apoptosis analysis were performed. ResultsCompared with the 25 K， CGNs nuclear pyknosis rate， cleaved Caspase-3 and ATM protein expression level were increased in the 5 K and ATM-specific inhibitor groups. The mRNA and protein expression levels of ATM and GADD45α were effectively reduced after transfection of ATM and GADD45α specific siRNA in C6 cells and CGNs. Compared with control， CGNs transfected with ATM specific siRNA showed a higher nuclear pyknosis rate. Totally 835 genes were identified to be up-regulated and 848 genes to be down-regulated in the Ku55933 treatment group； 454 genes were identified to be up-regulated and 314 genes to be down-regulated in the Ku6 treatment group； 274 genes were co-up regulated in the Ku5 and Ku60019 treatment groups， while 179 genes were co-down-regulated in the Ku5 and Ku6 treatment groups and the expression of ATM downstream target GADD45α was upregulated. The enrichment results showed that TNF signaling pathway， NF-κB signaling pathway and Apoptosis signaling pathway were significantly enriched. Compared with control， mRNA and protein expression levels of GADD45α were increased in inhibitor treatment and 5 K， while knocking down GADD45α resulted in a decrease in nuclear pyknosis rate in the Ku60019 and 5 K treatment group. ConclusionLoss of ATM activity induces GADD45α-dependent cerebellar granular neuronal apoptosis.