OBJECTIVE To provide a reference for improving postoperative pain management outcomes， accelerating patient recovery， and ensuring the safe use of opioids. METHODS A prospective cohort study was conducted， in which patients undergoing elective hip or knee replacement in the Department of Orthopedics at Baoding No.1 Central Hospital （hereinafter referred to as “our hospital”） from November 2021 to November 2023 were randomly divided into control group and observation group using a random number table， with 178 cases in each group. Patients in the control group received postoperative pain management implemented by medical staff according to the clinical pathway for perioperative pain treatment. Patients in the observation group， under the enhanced recovery after surgery model， received postoperative pain management through a multidisciplinary collaborative team including clinical pharmacists. The occurrence and resolution of opioid-related drug-related problems （DRPs） were compared between the two groups， and the DRPs were classified and analyzed using the Pharmaceutical Care Network Europe Classification System （V9.1）. Postoperative pain scores， sleep quality scores， length of hospital stay， and incidence of adverse reactions were compared between the two groups. RESULTS A total of 162 opioid-related DRPs were identified in 2 groups， with 58 in the observation group （identified 52 patients） and 104 in the control group （identified 91 patients）， showing a statistically significant difference （P＜0.05）. The primary issue involved in the DRPs for both groups was therapeutic effectiveness. Clinical pharmacists in the observation group conducted 88 interventions for the identified 58 opioid-related DRPs， achieving an overall intervention success rate of 84.5%. The pain scores and sleep quality scores from postoperative day 1 to 7， the length of hospitalization for hip replacement， the average hospitalization duration， and the total incidence of opioid-related adverse reactions were all significantly lower or shorter in the observation group compared to the control group （P＜0.05）. Furthermore， the main time effect， time-group interaction effect for pain scores and sleep quality scores were statistically significant in both groups （P＜0.05）， indicating that the control group exhibited greater reductions in these scores and observation group exhibited more rapid improvements. CONCLUSIONS The full involvement of clinical pharmacists in postoperative pain management and opioid medication administration in the orthopedics department enables timely identification and intervention of DRPs， enhance postoperative analgesia efficacy， decrease adverse drug reactions， shorten hospital stays， and accelerate patient recovery.

Mitochondria-associated membranes(MAMs)are a subcellular compartment involved in the communication and material exchange between the mitochondrial outer membrane and endoplasmic reticulum membrane.MAMs perform various biological processes in cells under different conditions.MAM-dysfunction-mediated calcium homeostasis imbalance,endoplasmic reticulum stress,mitophagy defects,mitochondrial fission/fusion dynamics imbalance,lipid metabolism disorders,and inflammatory responses are key pathogenic factors in Alzheimer's disease(AD).This article reviews the structure and function of MAMs,their involvement in AD pathology,and drug intervention targets,and discusses the role of MAMs in the pathogenesis of AD and the latest research into their mechanisms,to provide new ideas for the prevention and treatment of AD.

Objective To explore the value of serum leucine-rich-alpha-2-glycoprotein-1(LRG1)and CC motif chemokine ligand 19(CCL19)detecting levels in children with henoch-schonlein purpura nephritis(HSPN)for early clinical diagnosis and prognosis.Methods A sum of 108 children with HSPN who were treated at Handan Central Hospital from May 2021 to May 2023 were selected as the study subjects,meantime,72 healthy children were as the control group.The levels of LRG1,CCL19,IgM,IgA,and IgG in serum were detected.Logistic regression method was applied to analyze the influencing factors of HSPN,receiver operating characteristic was applied to evaluate the clinical value of LRG1 and CCL19 levels for early diagnosis of HSPN in children.The differences in serum LRG1 and CCL19 levels among children with HSPN in the acute,chronic,and recovery stages were analyzed,Spearman correlation was applied to analyze and explore the correlation between serum LRG1,CCL19 levels and the duration of HSPN in children.Results The levels of LRG1(184.36±23.64 ng/L)and CCL19(463.19±89.46 ng/L)in the HSPN group were obviously higher than those in the control group(149.42±18.29 ng/L,208.83±52.97 ng/L),and the differences were significant(t=10.600,21.710,all P＜0.05).The Logistic regression results showed that LRG1[OR(95％CI):1.429(1.057～1.933)]and CCL19[OR(95％CI):1.842(1.216～2.791)]were both influencing factors for the occurrence of HSPN in children(P＜0.05).According to the analysis of receiver operating characteristic(ROC),the areas under the curve(AUC)of serum LRG1,CCL19 and their combined diagnosis of HSPN in children were 0.868,0.881 and 0.952,respectively,and their combined application in clinical diagnosis was better than that of serum LRG1 and CCL19 in their separate diagnosis(Z=3.147,3.487,all P=0.001).The levels of LRG1(203.49±24.89 ng/L,177.56±23.19 ng/L)and CCL19(591.13±98.32 ng/L,415.61±89.82 ng/L)in the serum of HSPN patients in the acute and chronic stages were obviously higher than those in the rehabilitation stage(158.53±21.96 ng/L,295.17±69.61 ng/L),and the differences were significant(t=6.917,12.101;5.320,3.102,all P＜0.05),while the levels of LRG1 and CCL19 in the serum of HSPN patients in the acute stage were obviously higher than those in the chronic stage,and the differences were significant(t=5.059,8.750,all P＜0.05).Spearman correlation analysis showed that the serum levels of LRG1 and CCL19 in children with HSPN were positively correlated with their course of disease(r=0.506,0.689,all P＜0.001).Conclusion The levels of serum LRG1 and CCL19 are elevated in HSPN children,and combined detection of serum LRG1 and CCL19 can improve the early clinical diagnostic value of HSPN and evaluate the prognosis of children with HSPN.

Objective:To investigate the effect and mechanism of isorhynchophylline (IRN) on angiotensin Ⅱ(Ang Ⅱ)-induced cardiac hypertrophy.Methods:H9c2 cells were co-cultured with Ang Ⅱ and different concentrations of IRN (0, 5, 10, 25, 50 μmol/L). The cell surface area and mRNA levels of cardiac hypertrophy markers atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and β-myosin heavy chain (β-MHC) were detected to elucidate the effect of IRN on myocardial hypertrophy and the most effective concentration. H9c2 cells were co-cultured with Ang Ⅱ and IRN (25 μmol/L) at different times (0, 6, 12, 24 h) to elucidate the most effective time of inhibition. The phosphorylation levels of the signaling pathway were detected, and the effects of IRN and Akt inhibitor MK2206 on the phosphorylation levels of the signaling pathway were further explored to elucidate the underlying mechanisms.Results:Compared with the control group, the surface area of H9c2 cells, and the mRNA expression of myocardial hypertrophy markers ANP, BNP and β-MHC were significantly increased (all P<0.05). Pretreated with different concentrations of IRN (5, 10, 25, 50 μmol/L) could inhibit the increase in cell surface area induced by AngⅡ (all P<0.05), especially at the concentration of 25 μmol/ L ( P<0.01). IRN could time-dependently inhibit AngⅡ-induced activation of ANP, BNP, β-MHC mRNA (all P<0.05). AngⅡ caused increased phosphorylation levels of Akt, GSK3β, mTOR and FOXO3a. IRN could block AngⅡ-induced phosphorylation of the Akt signaling pathway. Conclusion:IRN attenuates AngⅡ-induced cardiomyocyte hypertrophy by inhibiting the Akt signaling pathway.

Objective To analyze the thyroid hormone levels in patients with acute ischemic stroke (AIS) and non-valvular atrial fibrillation (NVAF). Methods A total of 121 patients with AIS were selected, and were divided into NVAF group (AIS patients with NVAF) and control group (AIS patients without atrial fibrillation). Serum levels of triiodothyronine (T₃), free triiodothyronine (FT₃), thyroxine (T₄), free thyroxine (FT₄) and thyroid stimulating hormone (TSH) in two groups were measured and compared. The survival of the two groups was compared. Results The serum T₃ level in the NVAF group was significantly lower than that in the control group (P < 0.05). There were no significant differences in serum FT₃, T₄, FT₄ and TSH levels between the two groups (P>0.05). There was no significant difference in survival between the two groups (P>0.05). Conclusion NVAF is associated with serum T₃ levels in AIS patients. There is no correlation between the risk of death and NVAF in AIS patients.

Oral squamous cell carcinoma (OSCC) become a heavy burden of public health, with approximately 300 000 newly diagnosed cases and 145 000 deaths worldwide per year. Nucleotide metabolism fuel DNA replication and RNA synthesis, which is indispensable for cell proliferation. But how tumor cells orchestrate nucleotide metabolic enzymes to support their rapid growth is largely unknown. Here we show that expression of pyrimidine metabolic enzyme dihydroorotate dehydrogenase (DHODH) is upregulated in OSCC tissues, compared to non-cancerous adjacent tissues. Enhanced expression of DHODH is correlated with a shortened patient survival time. Inhibition of DHODH by either shRNA or selective inhibitors impairs proliferation of OSCC cells and growth of tumor xenograft. Further, loss of functional DHODH imped de novo pyrimidine synthesis, and disrupt mitochondrial respiration probably through destabilizing the MICOS complex. Mechanistic study shows that transcriptional factor SOX2 plays an important role in the upregulation of DHODH in OSCC. Our findings add to the knowledge of how cancer cells co-opt nucleotide metabolism to support their rapid growth, and thereby highlight DHODH as a potential prognostic and therapeutic target for OSCC treatment.
Carcinoma, Squamous Cell ; Cell Proliferation ; Head and Neck Neoplasms ; Humans ; Mouth Neoplasms ; Oxidoreductases Acting on CH-CH Group Donors ; SOXB1 Transcription Factors ; Squamous Cell Carcinoma of Head and Neck

Objective:To investigated the correlation between vascular remodeling pattern and perforator stroke after stenting in patients with symptomatic intracranial vertebrobasilar artery stenosis.Methods:Patients with symptomatic intracranial vertebrobasilar atherosclerotic stenosis underwent stenting and high resolution magnetic resonance imaging (HR-MRI) from January 2017 to August 2020 were enrolled retrospectively. The data of demography, vascular risk factors, plaque characteristics, operation process and postoperative complications were collected. The plaque characteristics were observed by HR-MRI, and the correlation between vascular remodeling pattern and perforator stroke after stenting was analyzed.Results:A total of 41 patients were enrolled in the analysis. Their age was 60.1±8.8 years (range, 49-77 years). There were 31 males (75.6%). Among them, 21 (51.2%) were positive remodeling, 20 (48.8%) were non-positive remodeling, and 5 (12.2%) had perforator stroke after procedure. The incidence of perforator stroke in the positive remodeling group was significantly higher than that in the non-positive remodeling group (23.8% vs. 0%; P=0.048). The positive remodeling rate of the perforator stroke group was significantly higher than that of the non-perforator stroke group (100.0% vs. 44.4%; P=0.048). Conclusions:Patients with intracranial vertebrobasilar atherosclerotic stenosis and positive vascular remodeling were more likely to have perforator stroke after stenting.

Objective:To explore the effect of Hsp22 on the activation of cardiac fibroblasts stimulated by TGFβ1 and its possible molecular mechanism.Methods:Cardiac fibroblasts of adult mice were isolated and cultured, and stimulated with TGFβ1 to induce fibroblast activation. Fibroblasts were incubated with Hsp22 of different concentrations (1, 2, 4, 8, 10 μg/mL) for 24 h, and their activation, proliferation and secretion were observed. CCK8 kit was used to detect cell proliferation. RT-PCR was used to detect the transcription of fibrogenic factor. Immunofluorescence was used to detect the expression of α-SMA protein. Immunoblotting was used to detect the possible signal protein.Results:CCK8 results showed that fibroblast increased significantly after TGFβ1 stimulation ( P<0.05). The expression of α-SMA in fibroblasts and the transcription of fibrosis-related genes increased significantly after TGFβ1 stimulation ( P<0.05). Different concentrations (1, 2, 4, 8, and 10 μg/mL) of Hsp22 all inhibited the proliferation of fibroblasts significantly (( P<0.05). Eight μg/mL and 10 μg/mL Hsp22 inhibited the expression of α-SMA ( P<0.05). and reduced the transcription of fibrosis-related genes ( P<0.05). Immunoblotting results indicated that after induced by TGFβ1, the expression of WNT and β-catenin, the phosphorylation level of GSK3β, and the nuclear translocation of β-catenin increased ( P<0.05). Ten μg/mL Hsp22 inhibited the expression of WNT and β-catenin, and reduced the phosphorylation of GSK3β the nuclear translocation of β-catenin and the phosphorylation of smad2 and smad3( P<0.05). Conclusions:Hsp22 could block TGFβ1-induced fibroblast activation, proliferation and secretion via inhibiting the WNT/β-catenin signaling pathway.

Objective:To explore the influence factors of chromosomal aberration levels in radiation workers in hospitals.Methods:Two hundred and fourteen age- and sex- matched hospital radiation workers were recruited by stratified random sampling method. According to the job title, the individuals were divided into four groups including diagnostic radiology group ( n=57), radiotherapy group ( n=49), nuclear medicine group ( n=52) and interventional radiology group ( n=56). Chromosomal aberrations in peripheral blood lymphocytes from the subjects were measured using conventional cytogenetic analysis method, and the influence factors of chromosomal aberrations were analyzed. Results:There was significant difference in the frequencies of acentric fragment, translocation and total chromosome-type aberrations among the four groups ( χ2=9.906, 19.965, 32.824, P<0.05), and the rates of aberrations were significantly higher in the interventional radiology group and the nuclear medicine groups than those in the diagnostic radiology (interventional group: χ2=4.711, 10.798, 10.845, P<0.05; nuclear medicine group: χ2=3.853, 7.674, 7.708, P<0.05) and the radiotherapy groups (interventional group: χ2=9.209, 9.772, 21.330, P<0.05; nuclear medicine group: χ2=8.010, 6.969, 10.812, P<0.05). The rates of translocation and total aberrations ( χ2=7.706, 6.667, P<0.05) and the frequencies of acentric fragment, translocation and total aberrations ( χ2=12.263, 15.360, 21.478, P<0.01) were dependent on the length of service and the dose among different groups. The rates of translocation and total aberrations significantly increased along with exposure doses ( r=0.347, 0.263, P<0.01). Poisson regression analysis indicated that the job titles and annual effective dose partly affected the levels of chromosomal aberrations[ IRR=1.797 (nuclear medicine group), 2.136 (interventional group) and 1.422 (0.5-1 mSv group); P<0.05]. Conclusions:The frequencies of chromosomal aberrations in the radiation workers of interventional and nuclear medicine groups remain higher levels in hospital, thus it is necessary to strengthen the radiation protection on these radiation workers.

Objective:To explore the advantage of dose estimation based on semi-automated dicentric (dic) scoring and the feasibility of reflecting a large scale radiation accident for population clinical triage by mean of the comparison between semi-automatic and manual detection.Methods:Human peripheral blood samples from two healthy volunteers were irradiated by 60Co γ-rays at the doses of 0, 0.5, 1, 2, 3, 4, 5 and 6 Gy with a dose rate of 0.27 Gy/min, and chromosome preparation was carried out using the conventional method. The dic and dic plus ring were analyzed automatically with the DCScore software and manually with the Ikaros software, respectively, in a high-throughput chromosome automatic scanning system. The dose-response curves were fitted with dic or dic plus ring per cell. Twelve standard samples of biodosimetry were used to validate the dose-response curves. Results:The numbers of dic or dic plus ring per cell by semi-automatic or manual detection increased with the exposure doses ( r=0.984, 0.972, 0.972, P<0.01). The yields of semi-automated dic or manually detected dic plus ring were well fitted with the correlation coefficients ( R2=0.998, 0.999, 0.999, P<0.01). When the exposure dose of the standard samples was more than 2 Gy, the relative deviation between actual and predict doses was within 21% using the dose-response curve based on automated dic before human verification and correction of dic (elimination of false positives and inclusion of true positives), and wiht ±10% after manual elimination of false positive dic. Bio-doses estimated from the dic detected by manual scoring were similar to the actual exposure doses with the exception of 0.7 Gy, but the efficiency of semi-automatic analysis of dic was increased by 6-times in bio-dose assessment. Conclusions:The semi-automated dic detection obviously improves the level and efficiency of biodosimetry analysis, and thus can meet the requirements of clinical classification diagnosis of medical emergency response to large-scale nuclear radiation events.