OBJECTIVE To establish a full-cycle management model for type 2 diabetes mellitus （T2DM） patients led by clinical pharmacists. METHODS Based on literature research， a basic framework and items of full-cycle management model led by clinical pharmacists were initially formulated. The Delphi method was adopted to conduct questionnaire inquiries among 26 experts to determine the specific implementation items of the model. The analytic hierarchy process （AHP） method was used to determine the weight values of items at all levels， and the reliability and validity of the model items were analyzed. RESULTS The recovery rates of the two rounds of expert consultation questionnaires were 86.67% and 100%， respectively， and the expert authority coefficient was 0.88. Kendall’s concordance coefficients of the tertiary-level items were 0.064 and 0.084， respectively， and the P values from the χ 2 tests were all less than 0.05； the consistent ratios of the judgment matrices for all levels of AHP model were all less than 0.1. The established full-cycle management led by clinical pharmacists comprised three primary-level items （pharmacy service pathway for T2DM patients during hospitalization， pharmacy management pathway for hypoglycemia in T2DM inpatients， and the pharmacy follow-up pathway for T2DM discharged patients， with weights of 0.098， 0.568 and 0.334， respectively）， twelve secondary-level items （e.g. pharmaceutical care during hospitalization for 1 to 2 days， admission assessment and education， with weights ranging from 0.143 to 0.333） and thirty-seven tertiary-level items （e.g. assessment of medication compliance， verification of the medication plan for discharge， with weights ranging from 0.068 to 0.750）. Cronbach’s α coefficients for primary-level items and the overall questionnaire were 0.762， 0.879， 0.928 and 0.951， respectively. The item-level and scale-level content validity indexes were 0.967 and 0.808， respectively. CONCLUSIONS A full-cycle management model for T2DM patients led by clinical pharmacists has been constructed successfully， demonstrating high scientificity and reliability.

Nasopharyngeal carcinoma （NPC） is a malignant tumor originating from the mucosal epithelium of the nasopharynx. In recent years， its incidence and mortality rates have shown a continuous upward trend， and there is still a lack of therapeutic regimens with both favorable efficacy and safety in clinical practice. Mitogen-activated protein kinase （MAPK） signaling pathway plays a key regulatory role in biological processes such as cell proliferation， differentiation， apoptosis and invasion. It is widely involved in the occurrence and progression of NPC， and serves as an important target in the research field of anti-NPC therapy. This article systematically elaborates on the mechanism of action of the MAPK signaling pathway in NPC， and reviews the research status regarding the anti-NPC effect of active components of traditional Chinese medicine （TCM） and TCM compound prescriptions by regulating this signaling pathway. The results show that TCM active components， including flavonoids （luteolin， maackiain， baicalein， etc.）， alkaloids （picrasidine Ⅰ， tetrandrine， etc.）， terpenoids （bakuchiol， cantharidic acid）， as well as traditional Chinese medicine compound formulas （such as Biyan jiedu capsules and Yiqi jiedu formula） can exert effects including inducing autophagy and apoptosis of NPC cells， promoting pyroptosis， reversing drug resistance， blocking epithelial-mesenchymal transition， weakening cell stemness and arresting cell cycle progression by regulating the MAPK signaling pathway， thereby inhibiting the occurrence and development of NPC through multiple pathways.

Objective To analyze the disease burden and trends of bladder cancer in China and globally from 1992 to 2021.  Methods Using the GBD 2021 database, the incidence, prevalence, mortality, and disability-adjusted life years (DALYs) rates of bladder cancer in China and globally from 1992–2021 were analyzed. Average annual percentage change (AAPC) was calculated using Joinpoint regression. Subgroup analyses by sex and age were conducted, and a Bayesian age-period-cohort (BAPC) model was used to predict trends in age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) for the next 15 years.  Results In 2021, China reported 106 000 new cases (ASIR: 5.14/100 000), 571 000 prevalent cases (age-standardized prevalence rate, ASPR: 26.61/100 000), 43 000 deaths (ASMR: 2.34/100 000), and a DALY rate of 45.31/100 000. From 1992–2021, China showed upward trends in ASIR and ASPR but declines in ASMR and DALYs, while global ASIR, ASMR, and DALYs decreased overall with slow ASPR growth. The peak cases in China and globally were both concentrated in the 65-79 age group, with a significantly higher burden on males than females. In China, smoking-related ASMR and ASDR exceeded global averages and rose, whereas high glucose-related indexes were lower and declined. Projections for 2021–2036 indicated that the global incidence and mortality rates would be rising, but ASIR/ASPR would be declining, while in China, the incidence rate would continue to rise, and the mortality rate will stabilize, with a significant increase in ASIR and a gradual decrease in ASPR.  Conclusion From 1992 to 2021, the incidence of bladder cancer in China has shown a continuous upward trend and is projected to persist in the future, with significant gender and age differences. Particular attention should be given to elderly males aged 85-89. The disease burden of bladder cancer attributable to smoking continues to rise, highlighting the urgent need to strengthen tobacco control policies.

Objective: To investigate the damaging effects of red blood cell supernatant (RBC-S) stored for different durations (7 d, 14 d, and 28 d) on vascular endothelial cells, and to explore the underlying mechanisms using bioinformatics analysis, so as to provide references for optimizing red blood cell transfusion strategies. Methods: Human umbilical vein endothelial cells (HUVECs) were co-cultured with RBC-S stored for 7, 14 and 28 days, designated as the 7 d group, 14 d group and 28 d group respectively, which were collectively defined as the experimental groups. Cell damage was evaluated by cell proliferation assay (Cell Counting Kit8, CCK8), lactate dehydrogenase (LDH) release assay, 4′, 6diamidino2phenylindole (DAPI) staining, and flow cytometry for apoptosis and reactive oxygen species (ROS) levels. The damage degree of RBC-S on vascular endothelial cells was assessed by statistical analysis of damage data among different groups. Since the damage effect reached a plateau at all time points, the 28 d storage group was selected as the representative for further mechanistic studies. Transcriptomic analysis was performed to explore the role of frizzled class receptor 1 (FZD1) and Wnt signaling pathway in red blood cell storagerelated endothelial dysfunction. Results: Compared with the control group, the storage groups treated with 7 d, 14 d, and 28 d RBC-S showed significantly decreased cell proliferation rates [control group 100%, 7 d group (69.51±2.30)%, 14 d group (74.54±2.89)%, 28 d group (73.59±2.36)%, P<0.05], significantly reduced numbers of DAPI-stained cell nuclei [control group (213±12.5) per field, 7 d group (140.33±17.04) per field, 14 d group (152.00±23.72) per field, 28 d group (144.33±19.09) per field, P<0.05] and significantly increased LDH release [control group (1), 7 d group (8.33±1.41), 14 d group (9.23±0.83), 28 d group (9.16±0.60), P<0.05]. There was no significant difference in the degree of damage caused by RBC-S among different storage groups (P>0.05). With the prolongation of storage time, free hemoglobin (FHb) gradually increased [control group (not detected), 7 d (16.57±6.38) mg/L, 14 d (76.80±22.83) mg/L, 28 d (286.97±29.02) mg/L, P<0.05]. The apoptotic rate (20.53±2.94)% and ROS relative intensity (5.13±0.91) in the 28 d storage group were significantly higher than those in the control group (P<0.05). Transcriptomic analysis showed that FZD1 played a key role in vascular endothelial dysfunction induced by red blood cell storage and was closely related to the Wnt signaling regulatory network. Conclusion: RBC-S stored for 7 d, 14 d, or 28 d can all significantly damage vascular endothelial cells, and the damaging effect reaches a plateau at 7 d of storage. Mechanistic investigation of the 28 d group indicated that the downregulation of the FZD1/Wnt signaling pathway may play a critical role in vascular endothelial dysfunction induced by red blood cell storage, providing a theoretical basis for further optimizing red blood cell storage and transfusion strategies.

Objective:To study the effects of epidermal growth factor(EGF)on the coordinated motor behaviors and changes of nigrostriatal dopaminergic system under the impact of EGF in middle-aged rats.Methods:Healthy aged Sprague Dawley(SD)rats were subcutaneously administered EGF(0.1 mg/ml)in the dorsal region for 7 days.Adhe-sive removal test,tapered beam walking test and descending a wire mesh pole test were performed to detect the changes in the coordinated motor behaviors of rats as well as changes in the expression of tyrosine hydroxylase(TH)and dopa-mine transporter(DAT)of nigrostriatal dopaminergic system in rats.Results:Middle-aged rats showed reduced behav-ioral parameters of adhesive removal test,tapered beam walking test and descending a wire mesh pole test compared with those of adult rats(P<0.05),which were improved after treatment with EGF(P<0.05).The expression of TH and DAT in nigrostriatal dopaminergic system was down-regulated in middle-aged rats compared with that in adult rats(P<0.01),however,which were up-regulated after treatment with EGF(P<0.01).Conclusion:EGF can amelio-rate the decline in coordinated motor behaviors and increases the activity of nigrostriatal dopaminergic system in middle-aged rats.

Objective:To investigate the effects of low-frequency neuromuscular electrical stimulation combined with exercise training on the recovery of rectus abdominis after delivery.Methods:This study used a case-control design. A total of 150 postpartum women with diastasis recti abdominis who were admitted to Women and Infants Hospital of Zhengzhou from January 2023 to March 2024 were selected for the study. The patients were divided into a treatment group ( n = 75, receiving low-frequency neuromuscular electrical stimulation combined with exercise training) and a control group ( n = 75, receiving exercise training only) based on the different treatment methods used. Both groups underwent treatment for 8 weeks. The inter-rectus distance, abdominal core muscle strength, pain levels, and thickness of the bilateral rectus abdominis muscles were compared between the two groups. Results:After treatment, the inter-rectus distances at 3 cm above the umbilicus, at the umbilicus, and 3 cm below the umbilicus in the treatment group were all smaller than those in the control group ( t = -3.25, -3.49, -4.52, all P<0.05). The time taken for the treatment group to complete the level 1 test of the eight-level abdominal bridge test was significantly longer than that in the control group [(62.00 ± 7.03) seconds vs. (35.89 ± 6.88) seconds, t = 22.99, P<0.05]. The root mean square values of the transverse abdominis muscle on both the affected side and the healthy side during the stepping test in the treatment group were greater than those in the control group [(6.70 ± 0.92) vs. (5.64 ± 0.89), t = 7.17, P<0.05]. The scores for each item on the Global Pain Scale and the total score in the treatment group were significantly lower than those in the control group (all P<0.05). The thicknesses of the rectus abdominis muscles on both sides (left side: at the umbilicus, 3 cm below the umbilicus; right side: 3 cm above the umbilicus, at the umbilicus, and 3 cm below the umbilicus) in the treatment group were greater than those in the control group (all P<0.05). Conclusions:Low-frequency neuromuscular electrical stimulation combined with exercise training can promote the recovery of rectus abdominis function, reduce the inter-rectus distance, improve core muscle strength, increase the thickness of the rectus abdominis, and relieve pain.

AIM:To investigate the efficacy and safety of checkpoint inhibitor lenvatinib combined with Tirelizumab in the treatment of advanced he-patocellular carcinoma(HCC).METHODS:A retro-spective analysis was performed on 52 patients with advanced HCC treated with Renvatinib,tirelli-zumab or their combination from January 2021 to December 2022 in Zhongda Hospital Affiliated to Southeast University,with disease progression,death and intolerance as endpoints.Efficacy was as-sessed according to RECIST 1.1 criteria and follow-up was conducted up to June 2023.The main end-points of the study were objective response rate(ORR),disease control rate(DCR),progression-free survival,PFS)and security.RESULTS:The combina-tion therapy significantly improved ORR and mPFS in patients compared with tirelizumab or lenvatinib monotherapy.Compared with single tirellizumab or lenvastinib,there was no significant difference in the adverse reactions associated with the combina-tion treatment,suggesting that the combination of the two was generally well tolerated and the side effects are controllable.CONCLUSION:Lonvastinib combined with tirelizumab is more effective in the treatment of HCC,can significantly prolong PFS,and is generally well tolerated,which may be a po-tential treatment for advanced HCC.

Objective:To explore the relationship between suicide attempts,school bullying,and psychological resilience in children and adolescents with major depressive disorder(MDD)and school bullying and psychological resilience.Methods:A total of 784 patients with MDD aged 10 to 18 years were included.The Chinese version of the Olweus Bullying Victimization Questionnaire,Adolescent Psychological Resilience Scale,and a suicide attempt assessment were utilized to evaluate school bullying,psychological resilience,and suicide attempt.Stepwise logistic regression was applied to identify the associated factors of suicide attempts.Results:The occurrence of suicide at-tempts in children and adolescents with MDD was positively associated with physical bullying(OR=1.85,95％CI:1.14-3.02)and indirect bullying(OR=1.48,95％CI:1.06-2.04),and negatively associated with higher levels of goal focus(OR=0.62,95％CI:0.45-0.85)and positive cognition(OR=0.62,95％CI:0.45-0.85)at higher levels.Conclusion:Bullying significantly increases the risk of suicide attempts in children and adolescents with MDD,while higher psychological resilience could mitigate this risk.

Objective:To explore the feasibility of measuring the angle of progress(AOP)and the fetal head-perineum distance(HPD)by ultrasound to predict the duration of the second stage of labor.Methods:A to-tal of 135 full-term singleton primiparas who gave birth through vagina in Shandong Provincial Hospital Affiliated to Shandong First Medical University from September 2022 to June 2024 were selected.They all received medication for labor analgesia during labor,and the fetal position was determined as occipital anterior position by ultrasound when the cervix was fully dilated.AOP and HPD were measured during the contraction interval.All parturients were divided into group A(duration of the second stage of labor≤60 min),group B(60 min＜duration of the sec-ond stage of labor≤120 min)and group C(duration of the second stage of labor＞120 min).The differences of AOP and HPD among these groups were compared,and their predictive efficacy for vaginal delivery within 60min and 120min was evaluated.Results:①The AOP in group A was higher than that in group B.The HPD in group A was lower than that in group B.The differences were statistically significant(P＜0.01).The AOP in group B was higher than that in group C.The HPD in group B was lower than that in group C.The differences were statistically significant(P＜0.05).②The area under the ROC curve for AOP and HPD to predict a vaginal delivery within 60 min was 0.872 and 0.914,and the optimal cut-off value was 126.25°and 4.52 cm,respectively(P＜0.01).③The area under the ROC curve for AOP and HPD to predict a vaginal delivery within 120 min was 0.901 and 0.801,and the optimal cut-off value was 116.40°and 4.69 cm,respectively(P＜0.01).Conclusions:It is feasible to pre-dict the duration of the second stage of labor duration by measuring AOP and HPD using intrapartum ultrasound.

Objective To study NF1 gene variations in 10 suspected cases of neurofibromatosis type I(NF1)and their parents,thereby providing a basis for genetic counselling,clinical diagnosis,and treatment of this disease.Methods A total of 10 patients diagnosed with,or suspected of having NF1 at Northwest Women's and Children's Hospital from March to December 2023 were selected as study subjects.Whole exome sequencing(WES)was performed to analyse NF1 gene mutations in the patients and their parents,with the findings validated by Sanger sequencing.Results Pathogenic mutations were identified in 6 of the 10 families,with the remaining 4 cases showing no pathogenic gene mutations.In Family 1,a de novo mutation,c.6505A>T,was detected in the NF1 gene.In Family 2,a de novo mutation,c.6705-3C>A,was identified in the NF1 gene.In Family 3,a de novo mutation,c.6853delT,was detected in the NF1 gene.In Family 4,a de novo mutation,c.2446C>T,was found in the NF1 gene.In Family 5,a paternal mutation,c.6067T>A,was identified in the NF1 gene.In Family 6,a paternal mutation,c.2991_2993dup,was detected in the NF1 gene.Conclusion The identification of new mutation sites enriches the mutation spectrum of the NF1 gene.This study provides important guidance for genetic counselling and prenatal diagnosis,offering crucial information for families with reproductive needs.