ObjectiveTo investigate the effect of Fuzheng Huayu prescription on hepatocyte extinction and regeneration in fibrotic liver and its mechanism of action in promoting hepatocyte regeneration. MethodsMice were given intraperitoneal injection of CCl₄ for 6 weeks to establish a model of liver cirrhosis， and there were 10 mice in the model group， 10 in the sorafenib group， 10 in the Fuzheng Huayu prescription group， and 9 in the normal control group. Since week 4 of modeling， the mice in the Fuzheng Huayu prescription group and the sorafenib group were given the corresponding drug by gavage at a dose of 4.8 g/kg and 4 mg/kg， respectively， for three consecutive weeks， and those in the normal group and the model group were given an equal volume of sodium carboxymethyl cellulose. Serum liver function parameters were measured； the METAVIR scoring system was used to evaluate liver inflammation and fibrosis stage； Sirius Red staining and hydroxyproline （Hyp） content in liver tissue were used to evaluate collagen deposition； immunohistochemistry was used to measure the protein expression levels of type IV collagen， CD31， CD32b， Ki67， CyclinD1， glutamine synthetase， Wnt2， and HGF， and Western blot was used to measure the expression levels of Wnt2， LRP6， β-catenin， p-β-catenin， and CyclinD1 in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the model group， the Fuzheng Huayu prescription group and the sorafenib group showed the following changes： significant reductions in the serum levels of alanine aminotransferase and aspartate aminotransferase and the content of Hyp in liver tissue （all P<0.01）； a significant reduction in METAVIR score； significant reductions in the expression levels of type Ⅳ collagen and CD31 （all P<0.05） and a significant increase in the expression level of CD32b （P<0.01）； significant reductions in the number of parenchymal extinction lesions and significant increases in the expression levels of Ki67 and CyclinD1 in liver tissue （all P<0.01）； significant increases in the protein expression levels of Wnt2， LRP6， β-catenin， and CyclinD1 and a significant reduction in the protein expression level of p-β-catenin （all P<0.05）； significant increases in the number of cells stained positive for both CD32b and Wnt2. ConclusionFuzheng Huayu prescription can inhibit hepatic sinusoidal capillarization， improve the Wnt2 exocrine function of liver sinusoidal endothelial cells， activate the Wnt/β-catenin signaling pathway associated with hepatocyte regeneration， and finally reverse liver cirrhosis.

Objective:To consolidate the current evidences regarding the efficacy of vitamin D supplementation in age-related sarcopenia.Methods:In this systemic review, a comprehensive literature search of scientific research including journal articles and academic dissertations was performed in prominent databases such as PubMed, Web of Science, China National Knowledge Infrastructure (CNKI) and Wanfang Database platforms, spanning from January 31, 2014 to January 31, 2024. Two search protocols integrating keywords and citation tracking were adopted to ensure comprehensiveness of the literature. Using “vitamin D” “ergocalciferols” “cholecalciferol” “sarcopenia” “muscle mass” “muscle strength” “myopenia” “muscle loss” “muscle reduction” “gait speed” “grip strength” “handgrip” as the main key words, focusing on the systematic reviews, meta-analyses of randomized controlled trials (RCT), and individual RCT, the scientific evidence of individual vitamin D intervention on age-related sarcopenia was evaluated and summarized. Research concerning particular disease conditions, children and adolescents, menopausal women, athletes and other specific populations were excluded.Results:A initial search yielded 2 448 articles in Chinese or English. A total of 8 systemic reviews/meta-analysis and 22 individual RCT literatures were included in the final analysis. Although some earlier lower-quality studies reported subtle improvements in skeletal muscle strength with vitamin D supplementation, high-quality systematic reviews/meta-analysis over the past three years had not shown significant positive effects of vitamin D intervention on sarcopenia and its breakdown parameters, such as skeletal muscle mass, muscle strength, and muscle function. Furthermore, the efficiency was influenced to some extent by the participants′ baseline status, such as muscle health and vitamin D nutritional status.Conclusions:Present evidence does not robustly support the efficacy of sole vitamin D supplement on age-related sarcopenia. High-quality clinical trials are imperative to accumulate more robust evidence in the future.

Objective: : The facial nerve trace on the ipsilateral side of the vestibular schwannoma was reconstructed by diffusion tensor imaging tractography to identify the adjacent relationship between the facial nerve and the tumor, and to improve the level of intraoperative facial nerve protection. Methods: : The clinical data of 30 cases of unilateral vestibular schwannoma who underwent tumor resection via retrosigmoid approach were collected between January 2019 and December 2020. All cases underwent magnetic resonance imaging examination before operation. Diffusion tensor imaging and anatomical images were used to reconstruct the facial nerve track of the affected side, so as to predict the course of the nerve and its adjacent relationship with the tumor, to compare the actual trace of the facial nerve during operation, verify the degree of coincidence, and evaluate the nerve function (House-Brackmann grade) after surgery. Results: : The facial nerve of 27 out of 30 cases could be displayed by diffusion tensor imaging tractography, and the tracking rate was 90% (27/30). The intraoperative locations of facial nerve shown in 25 cases were consistent with the preoperative reconstruction results. The coincidence rate was 92.6% (25/27). The facial nerves were located on the anterior middle part of the tumor in 14 cases, anterior upper part in eight cases, anterior lower part in seven cases, and superior polar in one case. Intraoperative facial nerve anatomy was preserved in 30 cases. Among the 30 patients, total resection was performed in 28 cases and subtotal resection in two cases. The facial nerve function was evaluated 2 weeks after operation, and the results showed grade I in 12 cases, grade II in 16 cases and grade III in two cases. Conclusion : Preoperative diffusion tensor imaging tractography can clearly show the trajectory and adjacent position of the facial nerve on the side of vestibular schwannoma, which is beneficial to accurately identify and effectively protect the facial nerve during the operation, and is worthy of clinical application and promotion.

OBJECTIVE：To investigate the ro le of clinical pharmacists in the therapy of fetal tachycardia by oral administration of digoxin through mother. METHODS ：The clinical pharmacists participated in the whole process of drug therapy for a pregnant woman with fetal tachycardia. According to 31+6 weeks of gestation ，the fetal heart rate of 230 beats/min at admission，clinical pharmacists provided the suggestion for the doctor about the safety and blood concentration determination of digoxin in the treatment of fetal tachycardia by mother. The patient ’s blood potassium value was lower than the normal range ，and it was suggested that potassium should be supplemented before digoxin was used ，and the initial dose of digoxin was 0.5 mg per 12 h. On the 7th day in the hospital ，the dosage of digoxin should be adjusted to maintaining dose （0.25 mg per 12 h）；on the 11th day in the hospital ，the patient ’s blood sodium value was low ，and the clinical pharmacists gave diet guidance. At the same time ， the clinical pharmacists explained the adverse reactions of digoxin to the doctors ，nurses and patients ，and closely observed and educated the patients. RESULTS ：Doctors adopted the suggestions of the clinical pharmacists. The fetal heart rate decreased to 180 beats/min from hospital after 13 days of treatment. The maternal digoxin concentration remained stable. No adverse drug reactions occurred in the mother and infant. CONCLUSIONS ：Maternal and child safety should be taken into account in the medication of pregnant patients. The clinical pharmacists assisting doctors to formulate medication strategying ，and carrying out pharmaceutical care for patients ，can ensure the effectiveness and safety of medication for fetal tachycardia.

Objective To explore the clinical pharmacist participation in the treatment of pregnancy complicated with Clostridium difficile infection. Methods From the perspective of medications, clinical pharmacists followed evidence-based medical practice, combined pharmaceutical theory with clinical evidence and provided individualized pharmacy care in drug selection, dose adjustment, medication regime and liver protection treatment. Results Clinical pharmacists integrated into the treatment team to ensure the effectiveness and safety of medication in the patient with pregnancy. Conclusion The individualized pharmacy care improved the effectiveness of drug treatment.

Objective:To explore the role and mechanism of long non-coding RNA KCNQ1 overlapping transcript 1 (LncRNA KCNQ1OT1) in the migration, proliferation and invasion of hepatocellular carcinoma (HCC).Methods:The experimental method was conducted. The expression levels of LncRNA KCNQ1OT1 in HCC tissues and normal liver tissues in the StarBase database were collected. The experimental methods including real-time quantitative PCR, cell transfection, scratch assay, CCK8 assay, Transwell assay, Western blot were used to determine the expression, migration, proliferation, invasion of LncRNA KCNQ1OT1 in HCC cells and its relationship with phosphatidylinositol 3-kinase/phosphorylated AKT Protein (PI3K /p-AKT) signaling pathways. Observation indicators: (1) expression of LncRNA KCNQ1OT1 in HCC tissues and normal liver tissues; (2) the migration of HepG2, SMCC-7721 and MHCC-97H HCC cells after LncRNA KCNQ1OT1 gene knockdown; (3) the proliferation and invasion of HepG2, SMCC-7721 and MHCC-97H HCC cells after LncRNA KCNQ1OT1 gene knockdown; (4) effects of LncRNA KCNQ1OT1 gene knockdown on PI3K/p-AKT signaling pathways. Measurement data with normal distribution were expressed as Mean± SD, and comparison between groups was analyzed using the t test. The Kaplan-Meier method was used to calculate survival rates and draw survival curves. Results:(1) Expression of LncRNA KCNQ1OT1 in HCC tissues and normal liver tissues. The expression levels of LncRNA KCNQ1OT1 in 374 HCC tissues and 50 normal liver tissues from StarBase database were 3.320±0.017 and 1.470±0.025, respectively, showing a significant difference ( t=5.24, P<0.05). Results of gene expression profile interactive analysis showed that the 30-month disease-free survival rates of HCC patients with high and low expression levels of LncRNA KCNQ1OT1 were 41% and 55%, respectively, with a significant difference ( χ2=6.209, P<0.05). The relative expression of LncRNA KCNQ1OT1 in HepG2, SMCC-7721and MHCC-97H cells were 1.470±0.042, 3.300±0.032, 4.040±0.031, respectively, versus 1.000±0.022 in normal liver cells (LO2), showing significant differences ( t=17.66, 95.40, 114.20, P<0.05). (2) The migration of HepG2, SMCC-7721 and MHCC-97H HCC cells after LncRNA KCNQ1OT1 gene knockdown. ① Results of cell transfection showed that the relative expression levels of LncRNA KCNQ1OT1 in HepG2, SMCC-7721 and MHCC-97H cells after LncRNA KCNQ1OT1 gene knockdown were 0.350±0.016, 0.310±0.020, 0.380±0.018, respectively, versus 1.000±0.021, 1.000±0.018, 1.000±0.019 in the negative control cells, showing significant differences ( t=23.40, 28.15, 22.32, P<0.05). ② Results of scratch assay showed that the healing rates of HepG2, SMCC-7721, MHCC-97H cells after LncRNA KCNQ1OT1 gene knockdown were 85.0%±1.9%, 75.0%±1.8%, 90.0%±1.7%, respectively, versus 100.0%±2.0%, 95.0%±1.8%, 72.0%±1.7% of the negative control cells, showing significant differences ( t=31.35, 47.36, 38.42, P<0.05). ③ Results of Transwell assay showed that the vertical migration rates of HepG2, SMCC-7721, MHCC-97H cells after LncRNA KCNQ1OT1 gene knockdown were 195±10, 205±12, 85±8, respectively, versus 520±11, 430±7, 405±20 of the negative control cells, showing significant differences between them ( t=922.30, 458.20, 708.40, P<0.05). (3) The proliferation and invasion of HepG2, SMCC-7721 and MHCC-97H HCC cells after LncRNA KCNQ1OT1 gene knockdown. ① Results of CCK8 assay showed that 72-hour optical densities of HepG2, SMCC-7721, MHCC-97H cells after LncRNA KCNQ1OT1 gene knockdown were 1.370±0.018, 1.240±0.016, 1.360±0.020, respectively, versus 0.900±0.023, 1.740±0.032, 1.230±0.025 of the negative control cells, with significant differences ( t=10.79, 12.00, 7.56, P<0.05). ② Results of Transwell assay showed that the invasion numbers of HepG2, SMCC-7721, MHCC-97H cells after LncRNA KCNQ1OT1 gene knockdown were 186±12, 155±7, 75±9, respectively, versus 505±1, 245±8, 300±15 of the negative control cells, showing significant differences ( t=955.90, 163.40, 530.90, P<0.05). (4) Effects of LncRNA KCNQ1OT1 gene knockdown on PI3K/p-AKT signaling pathways. Resluts of Western blot showed that the relative repression levels of PI3K in HepG2, SMCC-7721, MHCC-97H cells after LncRNA KCNQ1OT1 gene knockdown were 0.447±0.009, 0.430±0.012, 0.354±0.006, respectively, versus 0.820±0.017, 0.850±0.012, 0.531±0.001 of the negative control cells, showing significant differences ( t=18.94, 25.72, 27.46, P<0.05). The relative repression levels of p-AKT in HepG2, SMCC-7721, MHCC-97H cells after LncRNA KCNQ1OT1 gene knockdown were 0.343±0.015, 0.410±0.012, 0.579±0.006, respectively, versus 0.546±0.012, 0.620±0.012, 0.830±0.012 of the negative control cells, showing significant differences ( t=10.78, 12.86, 19.02, P<0.05). Conclusions:LncRNA KCNQ1OT1 plays an important role in the occurrence and development of HCC. LncRNA KCNQ1OT1 gene knockdown can inhibit the PI3K/AKT signaling pathways, so it can significantly inhibit the proliferation, migration and invasion of HCC cells.

Objective:To determine the concentration of hydroxychloroquine (HCQ) and its active metabolite deethylhydroxychloroquine (DHCQ) in breast milk of lactating patients with autoimmune disease. To observe the safety of hydroxychloroquine in lactation period, and to explore the factors that may affect HCQ and DHCQ concentration in the milk.Methods:Lactating patients with autoimmune disease who have taken HCQ for at least 6 months were included in our study. A new high performance liquid chromatography (HPLC) method was established to detect HCQ and DHCQ levels in breast milk. Milk samples were collected at different time points: before taking the drug (0 hours), and 2 hours, 4 hours, 6 hours after taking the drug. In addition, the genotype of cytochrome CYP3A4*1G, CYP3A5*3 and CYP2D6*10 which were related to HCQ metabolism were tested by dideoxy chain termination method. Visual acuity, hearing and growth status of the patients' infants were followed up on a regular basis. T-test, one-way ANOVA and Pearson's test were used for data analysis. Results:In 15 patients, the average concentration of HCQ and DHCQ in the milk of patients taking 200 mg/d were (520±261) ng/ml and (177±112) ng/ml, respectively. While the average concentration of HCQ and DHCQ in the milk of patients taking 400 mg/d were (1 036±374) ng/ml and (397±271) ng/ml, respectively. The peak of HCQ level for 11 patients was at 4 hour after taking the drug, while the others' were at 2 hour. The breast-fed infants did not show any abnormal symptoms of hearing, vision and growth. However, cytochrome gene polymorphism did not affect the peak of HCQ and DHCQ.Conclusion:The concentration of HCQ and DHCQ in breast milk is positively correlated to the dosage. The peak level of HCQ milk is 4 hours after taking the drug. The levels of HCQ and DHCQ at 6 hours are similar as those in the whole blood. It is suggested that patients who take HCQ can feed 4 hours after taking the drug to reduce the HCQ and its active metabolites being absorbed by infants. However, the impact of HCQ on infant safety and gene polymorphism of CYP on milk concentration among individuals needs to be further verified in large sample studies and long-term follow-up.

Objective To explore the clinical effect of intensive insulin therapy combined with ulinastatin in treatment of moderate to severe acute pancreatitis.Methods 70 patients were chosen due to sudden severe acute pancreatitis and received inpatient treatment,they were randomly divided into two groups(35 cases each)according to the different treatment,the control group received conventional treat-ment of acute pancreatitis combined with ulinastatin,combination group were based on the treatment of control group combined with intensive insulin therapy,analysing data between the two groups of patients in hospital time,,the third and seventh day of the APACHE-score before and after the treatment,white blood cells,red blood cell,platelet count,blood glucose,liver and kidney function,IL-6 and high sensitivity C-reactive protein(hs-CRP)changes.Results The time of hospitalization in the control group was(21.8 ± 13.2)days,the score of APACHE Ⅱ in the third day and seventh day were(10.5 ± 4.3)and(8.3 ± 3.1).The hospitalization time of the combined group was(18.9 ± 14.4)days and the third days,and the seventh days of APACHE Ⅱ score were(8.7 ± 3.2)and(5.7 ± 2.9)(P<0.05).The number of blood white blood cells,serum IL-6,hsCRP,alanine aminotransferase and serum creatinine between the two groups were also statistically significant after third and seventh days of admission(P<0.05).Conclusion Intensive insulin therapy combined with ulinastatin can significantly improve the short-term effect of in-patient treatment in patients with moderate to severe acute pancreatitis.

Objective To establish teaching cases evaluation questionnaire for problem based learning (PBL) in "Nursing Ethics".Methods Based on the literature review, the nursing ethics PBL teaching case evaluation questionnaire was established with the theoretical frame of teaching cases evaluation standard by China Case Center for Public Policy & Management (CCCPPM), consulting undergraduate professional certificate standard, combing the characteristics of PBL teaching and nursing ethics teaching, screening initialization questionnaire entries through theoretical analysis and interviewing 15 experts with a two-round Delphi survey.Results The positive coefficients of the two-round of expert consultation questionnaire were 93.75% and 100%. The expert coefficient of authority was 0.93. The nursing ethics PBL teaching case evaluation questionnaire containing 10 entries was established.Conclusions The preliminary establishment of PBL teaching case evaluation questionnaire of "Nursing Ethics" has a high scientificity and rationality, which can provide references for the research and practice of PBL teaching case evaluation in nursing ethics.

Objective To study the effects of transcranial magnetic stimulation (TMS) on learning and memory, and angiogenesis and the dendritic structure of hippocampal CA3 pyramidal neurons after cerebral infarction. Methods Forty-eight male Sprague-Dawley rats were divided into a sham operated group, a model group and a TMS group (n = 16). Rat models of focal cerebral infarction were established with unilateral middle cerebral artery (MCA) suture occlusion in the model and TMS groups. The rats of the TMS group were given 4 weeks of TMS treatment beginning 1 day after the infarction (2 times per day, 30 pulses per time). Their learning and memory abilities were tested with a Y-maze. Angiogenesis and the dendritic structure of their hippocampal CA3 pyramidal neurons were detected after 4 weeks. Results Compared with the model group, learning and memory improved significantly in the TMS group. The average microvessel density of the hippocampus in the TMS group was significantly more than in the model group. The total length of apical dendrites of hippocampal CA3 pyramidal neurons in TMS group was significantly longer than in the model group. Conclusions The improved learning and memory observed following TMS treatment are likely to be related to changes in angiogenesis, the dendritic.structure of the hippocampal CA3 pyramidal neurons, and enhanced synaptic plasticity.