Protein arginine methyltransferase 5 (PRMT5) exhibits elevated expression levels in a variety of cancers and has emerged as a critical target for cancer therapy in recent years. However, first-generation PRMT5 inhibitors have exhibited inadequate selectivity, leading to significant hematological toxicity, thus limiting their clinical utility. The second-generation PRMT5 inhibitors have shown marked improvement in safety and efficacy by selectively targeting MTAP-null tumor cells without impacting normal cells. This review systematically summarizes the biological and functional roles of PRMT5 in MTAP-deficient tumor cells, and comprehensively analyzes the research and development process, molecular binding mechanisms, and the latest advancements in clinical trials of the five second-generation PRMT5 inhibitors currently under investigation, aiming to provide valuable insights for further in-depth studies in this field.

Objective:To find out how newly recruited nurses feel about the use of scenario simulation teaching in communication skill training, and to provide references and lessons for improving and perfecting the training of newly recruited nurses.Methods:Purposive sampling method was used to select 10 nurses who were newly recruited to a tertiary grade A hospital in Shanghai in July 2023 for semi-structured interviews. Colaizzi's 7-step analysis method was used to collate and analyze the data and develop themes.Results:Three themes were extracted from the feelings of newly recruited nurses about scenario simulation teaching, which were the improvement of learning ability, the cultivation of clinical comprehensive ability, and the improvement of communication and teamwork ability.Conclusions:Scenario simulation teaching can improve the clinical communication ability of newly recruited nurses and enhance their learning ability and comprehensive clinical ability. This study designed a scenario simulation teaching program oriented and targeted to highlight communication ability, which further proved its positive significance. However, attention needs to be paid to the construction of clinical teaching team, evaluation system, and feedback mechanism for targeted improvement to enhance the teaching effect.

Objective To construct the machine learning models based on the radiomic features of non-contrast and enhanced CT and to evaluate the predictive value in the risk stratification of gastrointestinal stromal tumor(GIST).Methods A total of 182 patients with pathologically confirmed GIST were randomly divided into a training set and a validation set at a ratio of 7∶3.The volume of interest(VOI)was outlined in the non-contrast phase,arterial phase and venous phase,and its radiomic features were extracted.The most valuable radiomic features were selected using the least absolute shrinkage and selection operator(LASSO)algorithm.The logistic regression(LR)classifier was used to construct the prediction models based on single-phase or multi-phase images.The predictive efficacy of the different models was compared by using receiver operating characteristic(ROC)curves.Results Four,three,and four radiomic features were selected in the non-contrast phase,arterial phase and venous phase,and 4 models were constructed in total.Among the single-phase models,the venous phase had better predictive efficacy,with the area under the curve(AUC)of 0.932[95％confidence interval(CI)0.873-0.969]and 0.924(95％CI 0.819-0.979)in the training and validation sets.The predictive efficacy of the combined model was improved,with the AUC of 0.946(95％CI 0.891-0.978)and 0.938(95％CI 0.838-0.986).Conclusion The venous phase model can predict the risk stratification of GIST accurately,and the prediction efficacy can be improved by combining the non-contrast and arterial phases.

Objective·To evaluate the quality of clinical practice guidelines of obstructive sleep apnea(OSA)published worldwide.Methods·The guidelines of OSA were retrieved in PubMed,Embase,China National Knowledge Infrastructure(CNKI),Wanfang Data,SinoMed,MedSci,The Cochrane Library,and the websites such as Medlive,U.S.Preventive Services Task Force(USPSTF),National Institute for Health and Care Excellence(NICE),New Zealand Guidelines Group(NZGG),Scottish Intercollegiate Guidelines Network(SIGN),and Guidelines International Network(GIN)from establishment to December 2022.Two reviewers screened the literature and extracted the main information independently,using the Appraisal of Guidelines for Research and Evaluation Ⅱ(AGREE Ⅱ)and Reporting Items for Practice Guidelines in Healthcare(RIGHT)to evaluate the quality of the included OSA guidelines.Subgroup analysis was performed according to the publication regions of guidelines.The inter-evaluator consistency test was also performed and the results were expressed as the intra-class correlation coefficient(ICC).All the included guidelines were read entirely and the clinical questions they raised were summarized.Results·A total of 35 OSA guidelines were included.The ICC value of 0.975 showed a good inter-evaluator agreement.The results of AGREE Ⅱ showed that the average score of all guidelines was(63.60±16.45)%,with a minimum of 23.40%and a maximum of 91.67%.In the six domains,the scores of"Rigor of development"[(56.07±25.89)%]and"Applicability"[(53.57±15.52)%]were relative low.The average reporting rate of RIGHT of all the included guidelines was(67.84±20.03)%,with a minimum of 14.29%and a maximum of 94.29%,and the three domains with the lowest reporting rates were"Review and quality assurance"[(31.40±45.51)%],"Funding and conflict of interest declaration and management"[(56.43±33.95)%]and"Other aspects"[(56.19±36.85)%].Subgroup analysis showed that guidelines in Asian had a lower score in"Rigor of development"and a lower overall score of AGREE Ⅱ than the guidelines in America and Europe(both P<0.05),and the reporting rates in the domains of"Evidence"and"Other information"of RIGHT of the Asian guidelines were also lower than those in the guidelines in America and Europe(P<0.05).These guidelines focused on 42 clinical questions which were classified to 3 aspects,i.e.screening and diagnosis,treatment and long-term management of OSA.Conclusion·The quality of current global OSA guidelines varies a lot,and they need to be strengthened in terms of rigor of development,applicability,review and quality assurance,funding and conflict of interest declaration and management,especially those in Asia.

Objective:To evaluate the effect of ultrasound-guided subserratus anterior plane block on postoperative analgesia in patients un-dergoing laparoscopic radical gastrectomy.Methods:Sixty patients who underwent elective laparoscopic radical gastrectomy were enrolled between May 2022 and October 2023 at Tianjin Medical University Cancer Institute&Hospital.Patients were assigned into two groups us-ing a random number table method:the control(group C)and the ultrasound-guided serratus anterior plane block(SAPB)(group S).Patient-controlled intravenous analgesia(PCIA)was administered at the end of the surgery.After surgery,visual analogue scale(VAS)of static pain scores was evaluated at 1,6,12,24,and 48 hours.PCIA pump was started at the VAS pain score≥4 after surgery,and sufentanil 0.1μg/kg was intravenously injected when the efficacy was inadequate.The requirement for PCIA use,time to first postoperative anal exhaust,first postoperative out-of-bed activity,first oral intake,and the duration of hospitalization stay were recorded for the two groups.Results:VAS scores were significantly lower at postoperative 1,6,and 12 h in group S than in group C(P<0.05).Additionally,the number of effective uses of PCIA,and rescue analgesia were significantly lower in group S[(6.1±0.4)(2)]than in group C[(18.6±1.4)(17)](P<0.001).The time to first postoperative anal exhaust,first postoperative out-of-bed activity,first oral intake,and duration of hospital stay were shortened in group S than in group C(P<0.05).There were no significant differences in other parameters between these two groups.Conclusion:Ultrasound-guided SAPB can reduce postoperative pain and facilitate fast recovery in laparoscopic radical gastrectomy patients.

Objective: To investigate the differences in enolase and laminin levels in vaginal epithelial tissues between mice successfully infected withGardnerellaand mice not infected with Gardnerella, providing information for further exploration of the correlation between enolase and laminin levels and the incidence of bacterial vaginosis. Methods: Gardnerella strains isolated, purified, and identified from vaginal secretions of patients with bacterial vaginosis were used to infect the vagina of mice and establish a mouse model of bacterial vaginosis. Successful and failed mice was defined as successful and failed groups, respectively. Differential expression of enolase and laminin in the vaginal epithelial tissue of two groups of mice was detected by Western blot. Modeling success rate was statistically analyzed, and the expression differences of enolase and laminin was compared between two groups. Results: One strain of Gardnerella vaginalis infected 10 SPF grade KM mice, 7 mice met the diagnostic criteria for bacterial vaginosis, and 3 mice failed to model, with a success rate of 70%. Western blot was used to detect protein expression levels, and the levels of laminin and enolase in the successfully modeled mouse vaginal epithelial tissue were significantly higher than those in the failed modeling group, with statistical differences between the two groups(P<0.05). Conclusion Enolase and laminin may be involved in the occurrence of bacterial vaginosis, however, further research is needed to determine the mechanisms through which they trigger the occurrence and development of the disease.

Objective:To evaluate the role of neuronal nitric oxide synthase (nNOS)-nitric oxide synthase 1 adaptor protein (NOS1AP) coupling in remifentanil-induced hyperalgesia in rats.Methods:Forty clean-grade healthy adult male Sprague-Dawley rats, weighing 240-260 g, aged 2-3 months, were divided into 4 groups ( n=10 each) using a random number table method: control group (group C), remifentanil group (group R), nNOS-NOS1AP inhibitor ZLc002 group (group C+ Z) and remifentanil + ZLc002 group (group R+ Z). Normal saline was intravenously infused at a rate of 0.1 ml·kg -1·min -1 for 60 min in C group. Remifentanil was intravenously infused at a rate of 1.0 μg·kg -1·min -1 for 60 min in R group. ZLc002 10 mg/kg was intraperitoneally injected for 3 consecutive days, and then normal saline 0.1 ml·kg -1·min -1 and remifentanil 1.0 μg·kg -1·min -1 were intravenously infused for 60 min in C+ Z group and R+ Z group. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 24 h before intravenous infusion and 6, 24 and 48 h after intravenous infusion (T 0-3). All the rats were sacrificed after the last measurement of pain thresholds, and the L 4-6 segments of the spinal cord were removed for determination of the expression of nNOS, NOS1AP and Dexamethasone-induced Ras-related protein 1 (Dexras1) protein and mRNA using the real-time polymerase chain reaction. Nitrosylated proteins were extracted by biotin conversion for determination of the expression of nNOS, NOS1AP and total and nitrosylated Dexras1 (by Western blot) and co-expression of nNOS-NOS1AP (by co-immunoprecipitation). The content of NO in the spinal cord was measured. Results:Compared with group C, the MWT was significantly decreased, and the TWL was shortened at T 1-3, the expression of nNOS and NOS1AP protein and mRNA was up-regulated, the co-expression of nNOS-NOS1AP and NO production were increased, and the expression of nitrosylated Dexras1 was up-regulated in group R ( P<0.05), and no significant change was found in each aforementioned parameter in group C+ Z ( P>0.05). Compared with group R, the MWT was significantly increased, and the TWL was prolonged at T 1-3, the co-expression of nNOS-NOS1AP and NO production were decreased, the expression of nitrosylated Dexras1 was down-regulated ( P<0.05), and no significant change was found in the expression of nNOS and NOS1AP protein and mRNA in group R+ Z ( P>0.05). There were no significant differences in total Dexras1 protein and mRNA expression among the four groups ( P>0.05). Conclusions:The mechanism by which remifentanil induces hyperalgesia may be related to up-regulating the expression of nNOS and NOS1AP in the spinal cord, promoting interaction between nNOS and NOS1AP and mediating NO generation and Dexras1 nitrosylation modification in rats.

Objective:To evaluate the effect of ultrasound-guided internal branch of superior laryngeal nerve(ibSLN) block on the quality of anesthesia recovery in the patients undergoing intracranial tumor surgery.Methods:The data from patients of either gender, aged 18-65 yr, with a body mass index of 18-28 kg/m 2, who underwent intracranial tumor surgery from December 2022 to October 2023, were retrospectively collected. Patients were divided into control group (group C) and ultrasound-guided ibSLN block group (group U). Bilateral ibSLN block was performed with 0.375% ropivacaine hydrochloride 2 ml.The tracheal extubation time, emergence time, development of cardiovascular events within 15 min after extubation, emergence agitation, Ramsay sedation score, Steward recovery score, visual analogue scale scores at 10 min after extubation and development of postoperative sore throat and hoarseness in postanesthesia care unit were recorded. Results:Compared with group C, the incidence of emergence agitation, Ramsay sedation score, visual analogue scale scores and sore throat were significantly decreased, the incidence of hoarseness was increased ( P<0.05), and no significant change was found in the extubation time, emergence time and Steward recovery score in group U( P>0.05). No hypertension, hypotension, tachachycardia and bradycardia were found in two groups. Conclusions:Ultrasound-guided ibSLN block can improve the quality of anesthesia recovery in the patients undergoing intracranial tumor surgery.

Objective:To evaluate the role of Ras homolog gene family member A (RhoA) in hydrogen-induced alleviation of lipopolysaccharide (LPS)-caused damage to pulmonary microvascular endothelial cell(PMVEC) barrier function in mice.Methods:PMVECs were cultured in DMEM/F12 medium containing 10% fetal bovine serum and 1% penicillin/streptomycin until 4-6 passage. These cells were divided into 6 groups ( n=36 each) using a random number table method: control group (group A), hydrogen-rich medium group (group B), LPS group (group C), LPS + hydrogen-rich medium group (group D), LPS + RhoA inhibitor C3 enzyme group (group E) and LPS + hydrogen-rich medium + RhoA agonist U-46619 group (group F). Cells were cultured within normal medium in group A, group C and group E and within hydrogen-rich medium in group B, group D and group F. LPS at a final concentration of 1 μg/ml was simultaneously added in group C, group D, group E and group F. C3 enzyme at a final concentration of 3 μg/ml was added at 2 h before addition of LPS in group E. U-46619 at a final concentration of 10 mg/ml was added at 3 h before addition of LPS in group F. The expression of vascular endothelial (VE)-cadherin and occludin was determined by Western blot at 6, 12 and 24 h after incubation with LPS. At 24 h after incubation with LPS, the release rate of LDH was measured by LDH method, cell viability was measured by MTT method, and the activity of RhoA was determined by GST pull-down method. Results:Compared with group A, the expression of VE-cadherin and occludin was significantly down-regulated at 6, 12 and 24 h of incubation, the cell viability was decreased at 24 h of incubation, and the release rate of LDH and activity of RhoA were increased in group C ( P<0.05). Compared with group C, the expression of VE-cadherin and occludin was significantly up-regulated at 6, 12 and 24 h of incubation, the cell viability was increased at 24 h of incubation, and the release rate of LDH and activity of RhoA were decreased in group D ( P<0.05). Compared with group C, the expression of VE-cadherin and occludin was significantly up-regulated at 6, 12 and 24 h of incubation, the cell viability was increased at 24 h of incubation, and the release rate of LDH and activity of RhoA were decreased in group E ( P<0.05). Compared with group D, the expression of VE-cadherin and occludin was significantly down-regulated at 6, 12 and 24 h of incubation, the cell viability was decreased at 24 h of incubation, and the release rate of LDH and activity of RhoA were increased in group F ( P<0.05). Conclusions:RhoA is involved in hydrogen-induced alleviation of LPS-caused damage to PMVEC barrier function in mice.

Objective:To evaluate the effect of neoadjuvant chemotherapy combined with immunotherapy on the perioperative renal function in patients undergoing radical resection for esophageal cancer.Methods:This was a retrospective cohort study. Clinical data from patients undergoing neoadjuvant chemotherapy combined with immunotherapy for esophageal cancer in Tianjin Medical University Cancer Institute & Hospital and Tianjin University Chest Hospital from January 2020 to April 2022 were retrospectively collected. According to the preoperative treatment regimen, the patients were divided into neoadjuvant chemotherapy group (group nCT) and neoadjuvant chemotherapy combined with immunotherapy group (group nCT+ IT). nCT group underwent neoadjuvant chemotherapy, which included a platinum-based regimen combined with fluorouracil or taxanes. In nCIT+ IT group, programmed cell death protein 1 inhibitors were used for immunotherapy based on neoadjuvant chemotherapy. All the patients underwent 2-3 cycles of therapy, with each cycle lasting 21 days. Surgery was performed 4-6 weeks after the completion of the last therapy. The concentrations of serum creatinine, uric acid and blood urea nitrogen were detected before therapy, at 72 h before surgery and at 72 h after surgery. The acute kidney injury (AKI) diagnosed by the Kidney Disease: Improving Global Outcomes criteria at 72 h before surgery and 72 h after surgery were recorded. The pathological complete response rates, recurrence rate and disease-free survival time after surgery were collected.Results:Compared with group nCT, the serum urea concentration was significantly increased after treatment, the serum uric acid concentrations were increased at 72 h before surgery and 72 h after surgery, the pathological complete response rate was increased, the recurrence rate was decreased, the disease-free survival time was prolonged ( P<0.05), and no statistically significant changes were found in the incidence of AKI at 72 h before surgery and 72 h after surgery in group nCT+ IT ( P>0.05). Conclusions:Although neoadjuvant chemotherapy combined with immunotherapy can raise the pathological complete response rate and disease-free survival rate, it has a certain effect on renal function. Perioperative renal function testing should be strengthened to prevent the occurrence of AKI in the patients undergoing radical resection for esophageal cancer.