OBJECTIVE To analyze the potential adverse drug interactions （pADIs） of clarithromycin， and establish refined prescription pre-review rules. METHODS Outpatient prescriptions of clarithromycin in combination with other drugs were collected from January 1， 2024 to June 30， 2024 through hospital information system of the Third People’s Hospital of Bengbu. pADIs were identified and their risk severities were graded according to Lexicomp and Micromedex databases. Then， refined prescription pre- review rules for clarithromycin pADIs-related drugs were established according to the identification and risk level results. RESULTS Among 3 046 clarithromycin combined drug prescriptions， 946 cases of pADIs occurred in 812 prescriptions. There were 6， 415 and 525 cases classified as “contraindicated”，“ major” and “moderate”， respectively. The combination drugs with “contraindicated” levels were tamsulosin， rupatadine， domperidone and ticagrelor， while those with “major” levels were mainly theophylline， dexamethasone and amlodipine. Accordingly， 26 refined rules were established， including 4 items of “warning information→prescription interception”， 11 items of “warning information→prescription double signature” and 11 items of “attention information→prescription approval”. CONCLUSIONS There are “contraindicated” and “major” risks associated with clarithromycin and its combination drugs in the hospital， and refined prescription pre-review rules for clarithromycin combined drug prescription have been established successfully.

OBJECTIVE To analyze the potential adverse drug interactions based on pharmacokinetics （PK-pADIs） of gefitinib， and establish its corresponding prescription review rules. METHODS Outpatient prescriptions of gefitinib combination therapy in our hospital from January 1， 2022 to November 30， 2024 were collected through rational drug software system. PK- pADIs present in the prescriptions were identified based on the Drugs.com® drug interactions database. The specific combination drugs and cases of PK-pADIs were statistically analyzed， and prescription review rules were established according to the severity classification of PK-pADIs. RESULTS & CONCLUSIONS A total of 217 prescriptions of gefitinib combination therapy were enrolled. Among them， 28 prescriptions （12.90%）， involving a total of 28 patients， had 29 cases of PK-pADIs， with respiratory medicine prescriptions （22 prescriptions） being the main type. The combination drugs included proton pump inhibitors （13 cases）， strong cytochrome P450 3A4 （CYP3A4） inhibitors （7 cases）， H2 receptor antagonists （4 cases）， CYP3A4 inducers （3 cases）， and CYP2D6 substrates （2 cases）. The severity classifications for these interactions were severe， moderate， severe， moderate and moderate， respectively. Based on the above severity classification of PK-pADIs， four prescription review rules had been established as follows： when gefitinib was combined with acid-suppressing drugs， it should be subject to “manual review”； when gefitinib was combined with dexamethasone， metoprolol， or strong CYP3A4 inhibitors， an “alert” should be triggered， and the physician should be informed via an alert box to strengthen the monitoring of relevant indicators. Clinical pharmacists need to conduct in-depth training on knowledge related to gefitinib drug interactions in key clinical departments such as respiratory medicine. They should strengthen the monitoring and guidance of rational drug use for patients who are on long-term gefitinib therapy， and promptly identify and intervene in PK-pADIs， thereby enhancing the rationality， safety， and effectiveness of clinical drug use.

Objective To investigate the mechanism of iron death induced by TRPC6/NF-κB in glomerular podiocytes mediated by high homocysteine(Hcy).Methods Mouse glomerulopocytes were cultured in vitro and divided into Control group(0 μmol/L Hcy)and Hcy group(80 μmol/L Hcy).After 48h of intervention,Western blot was used to detect the expression levels of iron death related proteins GPX4 and SLC7A11 and TRPC6 and NF-κ B.Real-time quantitative fluorescence PCR(qRT-PCR)and immunofluorescence were used to detect the expression of TRPC6.The level of podocyte apoptosis was detected by flow cytometry.Malondialdehyde(MDA)assay kit was used to determine intracellular MDA levels.After transfection of TRPC6 interference fragment and TRPC6 negative control(NC),qRT-PCR was divided into Control,si-NC and si-TRPC6(Si-TRPC6-1,Si-TRPC6-2,Si-TRPC6-3).Western Blot was divided into Control,Hcy,si-NC+Hcy,si-TRPC6+Hcy.The expression of TRPC6 mRNA was detected by qRT-PCR.The expression levels of GPX4,SLC7A11,NF-κB and TRPC6 were detected by Western Blot.The level of podocyte apoptosis after interference was detected by flow cytometry.Results(1)Compared with Control group,the expression levels of iron death related proteins GPX4 and SLC7A11 in Hcy group were decreased,and the apoptosis rate was increased(P<0.05).(2)Compared with Control group,TRPC6 protein,mRNA levels and immunofluorescence expression were increased in Hcy group.The level of MDA and the expression of NF-κB signaling pathway protein increased in Hcy group,and the comparison between the two groups had statistical significance(P<0.05).(3)Compared with the si-NC group,the mRNA expression level of TRPC6 in si-TRPC6(Si-TRPC6-1,Si-TRPC6-2,Si-TRPC6-3)group was decreased,and the interference effect of Si-TRPC6-3 was the best(P<0.05).After transfecting TRPC6 NC and TRPC6 interference fragment and administering Hcy,there was no difference in GPX4,SLC7A11,NF-κB and TRPC6 expression in si-NC+Hcy group compared with Hcy group.Compared with the si-NC+Hcy group,the si-TRPC6+Hcy group had higher expression of iron death related proteins,GPX4 and SLC7A11,lower expression of NF-κB and TRPC6,and decreased apoptosis rate(P<0.05).Conclusion This study confirmed that TRPC6/NF-κB can regulate iron death of renal podocytes under the induc-tion of Hcy,which is one of the mechanisms leading to kidney injury.

Objective To investigate the role of lncRNA SNHG1 in homocysteine-induced pyroptosis of podocyte.Methods Cbs+/-mice were randomly divided into two groups:a normal diet group(ND)and a high me-thionine diet group(HMD).Western blotting was used to detect the protein expression levels of Caspase-1,Cleaved Caspase-1,and NLRP3.Mouse renal glomerular podocytes were cultured in vitro,and then assigned into a control group(Control,0 μmol/L Hcy)and a homocysteine intervention group(Hcy,80 μmol/L Hcy).Western blotting was used to detect the protein expression levels of Caspase-1,Cleaved Caspase-1,and NLRP3.Mouse renal glomerular podocyion group(OE-NC + Hcy)and the lncSNHG1 overexpression + homocysteine intervention group(OE-SNHG1 + Hcy)were also established.After 48 hours of intervention,Real-time fluorescence quantita-tive PCR was used to detect the expression of lncSNHG1 in podocytes after Hcy intervention.Western blot was used to detect the expressions of Caspase-1,Cleaved Caspase-3 and NLRP3.Immunofluorescence was used to de-tect the expression levels of GSDMD and GSDMD-N.ELISA was used to detect the contents of IL-1β and IL-18.Results(1)In the animal experiments,the expression levels of pyroptosis-related proteins Caspase-1,Cleaved Caspase-1,NLRP3,GSDMD,and GSDMD-N were all increased in the HMD group compared with the ND group.(2)In the cellular experiments,the expression levels of Caspase-1,Cleaved Caspase-1,NLRP3,GSDMD,and GSDMD-N were all increased in the Hcy group compared with the Control group,and the contents of pyroptosis-mediated inflammatory factors IL-1β and IL-18 were increased as well.(3)In the cellular experiments,the expres-sion of lncSNHG1 was increased in the Hcy group compared with the control group.After transduction with lnc-SNHG1 lentivirus,the expression of lncSNHG1 was increased in the OE-SNHG1 group,compared with the control group and the OE-NC group.(4)In the cellular experiments,the expressions of pyroptosis-related proteins Cas-pase-1,Cleaved Caspase-1,NLRP3,GSDMD,and GSDMD-N were increased compared with the OE-NC+Hcy group,and the contents of pyroptosis-mediated inflammatory factors IL-1β and IL-18 were increased in the OE-SNHG1+Hcy group.Conclusion These results indicate that lncSNHG1 may play a role in promoting Hcy induced podocytepyroptosis.

Objective To study the efficacy of speech training combined with Montessori education on speech problems in children after velopharyngeal insufficiency surgery.Methods A retrospective analysis of 63 cases of children who underwent velopharyngeal repair at Children's Hospital of Soochow University between January 2019 and December 2021 was conducted.Subjects were divided into three groups.A total of 21 patients who received family rehabilitation training after the operation were divided into control group A,42 patients who received regular hospital rehabilitation training after the operation were divided into group B and group C,of which 21 patients in group B received routine speech training,and 21 patients in group C received Montessori education and routine speech training.Nasal resonance status,assessment of dysarthric intelligibility,and cranially positioned lateral radi-ographs when pronouncing/i/sounds were evaluated individually before treatment and 6 months after treatment.The improvement of velopharyngeal function,nasal resonance status,and dysarthric articulation were evaluated.Results After the six-month intervention,the dysarthric speech intelligibility were significantly improved in three groups with improvement of 35.45％in group A,43.66％in group B,and 49.33％in group C,respectively(P＜0.05).The improvement rate of nasality reached 100％in the B and C group with nasality elimination rate of 70％in group B and 95.24％nasality elimination in group C,and the efficacy of the two groups was statistically signifi-cant(P＜0.05).During phonation of the/i/tone,velopharyngeal insufficiency was observed in seven patients in group B and in only one patient in group C,and the efficacy was statistically significant in both groups(P＜0.05).Conclusion Postoperative targeted speech training is necessary in patients with velopharyngeal insufficiency,and speech training combined with Montessori education can significantly improve the function of velopharyngeal clo-sure,thus achieving a good state of nasal resonance and correct articulation as early as possible.

Objective:To review the current research and existing problems of symptom cluster sentinel symptoms in cancer patients both domestically and internationally, so as to provide reference for future research.Methods:The literature on sentinel symptoms of cancer symptom clusters, from the establishment of the database until November 8, 2023, was electronically searched on platforms such as China National Knowledge Infrastructure, WanFang Data, VIP, China Biomedical Database, PubMed, Web of Science, Cochrane Library, Embase and so on. Descriptive statistical analysis was conducted.Results:Sixteen articles were included, with an overall upward trend in publication volume, including 10 Chinese articles and 6 English articles. The sentinel symptom hotspots of cancer patients' symptom clusters mainly included: (1) the number of symptoms included in the analyzed symptom clusters was 3 to 13, the number of symptom clusters was 1 to 8, and the number of sentinel symptoms explored in each literature was 1 to 8; (2) Identification and dynamic changes of sentinel symptoms in symptom clusters; (3) Differences in sentinel symptoms among different symptom groups of cancer patients; (4) Analyzing specific sentinel symptoms of symptom groups based on different statistical methods; (5) Intervention based on sentinel symptoms of symptom clusters.Conclusions:In recent years, the symptom cluster sentinel symptoms of cancer patients have received attention from researchers at home and abroad, but there are problems such as uneven development and inconsistent research methods. High quality identification research is needed to make the included population specific and the methods scientifically unified, and to focus on the impact and mechanism of symptom cluster sentinel symptoms on patient outcomes in symptom clusters, so as to investigate potential mechanisms and promote effective symptom management.

Objective:To observe the effect of rich environmental rehabilitation training on the physical system and ner-vous system development of newboms with hypoxic-ischemic encephalopathy(HIE). Method:Sixty-one HIE newboms were divided into the observation group(n=31)and the control group(n=30).The control group was given the routine clinical treatment and care,and the observation group was supplemented with enriched environmental rehabilitation training on the basis of the control group for 3 weeks.The body length and weight,and the head circumference of the two groups were measured to assess the physical development at admis-sion and 3 weeks after the intervention,and the neonatal behavioral neurological assessment(NBNA)and test of in-fant motor performance(TIMP)were used to evaluate the neurological development and motor function. Result:After the intervention,the changes of body length and weight changes in the observed group were bet-ter than the control group(P＜0.05),no significant difference in head circumference(P＞0.05),and the NB-NA score and TIMP score were higher than those of the control group(P＜0.05). Conclusion:The application of rich environmental rehabilitation training can promote the rapid development of physique and nervous system of the newboms with HIE and improve the motor function.

Objective:To understand and explore the incidence and influencing factors of malnutrition in patients with inflammatory bowel disease.Methods:This study was a cross-sectional study. Patients with inflammatory bowel disease hospitalized in the Department of Gastroenterology of a tertiary hospital in Shenzhen from March 1 to August 31, 2021 were enrolled. Indicators related to nutrition and clinical outcome were collected, including height, weight, body mass index (BMI), nutritional risk screening (NRS 2002) results, malnutrition diagnosis as per Global Leadership Initiative on Malnutrition (GLIM) criteria and Pittsburgh Sleep Quality Index (PSQI). Chi-square test, t-test and Wilcoxon rank sum test were used as appropriate for univariate analysis, and binary logistic regression analysis was used for multivariate analysis.Results:A total of 188 patients were included in this survey. There were 145 (77.1%) patients with no malnutrition, 38 (20.2%) with moderate malnutrition, and 5 (2.7%) with severe malnutrition according to GLIM criteria. In the subgroup of 47 ulcerative colitis patients, 12 (25.5%) were with moderate malnutrition and 3 (3.4%) were with severe malnutrition. In the subgroup of 141 Crohn's disease patients, 26 (18.4%) were with moderate malnutrition and 2 (1.4%) were with severe malnutrition. When divided by the presence or absence of malnutrition, there were statistically significant differences in age ( t = -2.237, P = 0.026), disease stage ( χ 2 = 22.299, P < 0.001), history of digestive tract resection ( χ 2 = 6.890, P = 0.009), intestinal infection ( χ 2 = 4.010, P = 0.045), gastrointestinal symptoms ( χ 2 =11.884, P = 0.001), hemoglobin ( t = 5.160, P < 0.001), serum albumin ( t = 3.96, P < 0.001), prealbumin ( t = 5.061, P < 0.001) and PSQI scores ( t = -4.744, P < 0.001). Multivariate analysis showed that the stage of disease, history of partial resection of digestive tract, gastrointestinal symptoms, hemoglobin, prealbumin and PSQI scores were the main influencing factors of malnutrition. Conclusions:IBD patients at older age, at active stage, and with history of partial digestive tract resection, intestinal infection, gastrointestinal symptoms, low hemoglobin, low serum albumin, low prealbumin and poor sleep quality are more likely to develop malnutrition. Timely intervention should be carried out to improve the nutritional status of these patients.

Objective:To establish a three-dimensional model of locking plate fixation for 42A2 type oblique tibial fractures with different fracture line directions and different angles between the fracture line and the long axis of the tibia. Finite element analysis was used to calculate and analyze the biomechanics of locking plate, screw, and tibia, providing theoretical basis for clinical application.Methods:A healthy adult volunteer, 25 years old, male, with a height of 173 cm and a weight of 69.5 kg, was selected to perform computed tomography (CT) scans on the left tibia. Relevant data were obtained to establish a locking steel plate fixation model for 42A2 type tibia with different oblique fracture line directions and different angles between the fracture line and the long axis of the tibia. Eight hole pure titanium plates were used for fixation, respectively. We compared the Mises stress changes of locking plates, screws, and tibia in different angle fracture models.Results:In the case of a 42A2 type fracture in the left oblique direction with a fracture line from outside to inside, the maximum Mises stress in the tibia was 114 MPa, the maximum Mises stress in the screw was 279.8 MPa, and the maximum Mises stress in the locking steel plate was 302.4 MPa; In the case of a 42A2 type fracture in the right oblique fracture with a fracture line from the bottom to the top, the maximum Mises stress of the tibia was 93.41MPa, the maximum Mises stress of the screw was 353.4 MPa, and the maximum Mises stress of the locking steel plate was 411.8 MPa.Conclusions:Regardless of the oblique fractures in both left and right directions, the maximum stress values are: locking plate>screw>tibia; When the position of the locking steel plate is fixed, the maximum stress values of the locking steel plate and screw are both right oblique fracture>left oblique fracture; And the maximum stress values all increase with the increase of angle.

Objective:To compare the differences of short and long-term outcomes between laparoscopic surgery and open surgery treatment of intrahepatic cholangiocarcinoma patients.Methods:A retrospective cohort study was conducted to collect the clinical data of 118 patients with intrahepatic cholangiocarcinoma who underwent surgery in Qilu Hospital of Shandong University from January 2015 to June 2020. They were divided into laparoscopy group and open group according to the operation methods. The perioperative data, such as intraoperative surgical conditions, hospital costs, postoperative complications, postoperative blood biochemical tests, and the follow-up data of the two groups were compared.Results:In the laparoscopic group, there were 40 patients, 18 males and 22 females, aged (61.5±9.1) years. There were 78 patients in the open group, 48 males and 30 females, aged (61.2±8.3) years. The tumor size of the laparoscopic group was (4.4±1.8) cm, which was smaller than that of the open group (6.0±3.3) cm, and the differences were statistically significant ( P<0.05). In the laparoscopic group, 4 cases (10%) were converted to open surgery. The intraoperative blood loss, intraoperative blood transfusion proportion, 3 or more liver segments resection proportion and hospital costs of laparoscopic group were lower than those of open group [200.0(100.0, 261.8) ml vs. 300.0(100.0, 400.0) ml, 5.0%(2/40) vs. 26.9%(21/78), 37.5%(15/40) vs. 66.7%(52/78), (6.2±2.0) wan yuan vs. (7.2±2.3) wan yuan], the differences were statistically significant (all P<0.05). There were no significant differences in the incidence of postoperative complications between the two groups ( P>0.05). On the first post-operative day, ALT serum level and the third post-operative day TBil serum level in the laparoscopic group were lower than those in the open group [188.5(130.5, 274.0) U/L vs. 320.0(144.0, 427.0) U/L, 26.4(18.3, 26.4) μmol/L vs. 31.6(18.8, 37.5) μmol/l], the differences were statistically significant ( P<0.05). There were no significant differences in 1-year and 2-year overall survival rate and disease-free survival rate between the two groups ( P>0.05). Conclusion:Compared with open surgery, laparoscopic surgery in the treatment of intrahepatic cholangiocarcinoma has better short-term outcomes, and can achieve similar results in medium- or long-term outcomes.