OBJECTIVES: To investigate the effects of different filtration fractions (FFs) during continuous venovenous hemodiafiltration (CVVHDF) post-dilution. METHODS: This study employed a single-blind, head-to-head randomized controlled design. Patients who underwent daytime continuous renal replacement therapy (CRRT) in the Department of Nephrology, the Second Affiliated Hospital of Nanchang University between April 2022 and June 2023 were prospectively enrolled. They were randomly assigned to either a low FF group (FF set at 20%-<25%) or a high FF group (FF set at 25%-30%). All patients received post-dilution CVVHDF with systemic heparin anticoagulation. The primary outcome was extracorporeal circuit coagulation, comprehensively assessed through dynamic monitoring of arterial pressure, venous pressure, and transmembrane pressure, combined with filter clotting grading at the end of the session. Secondary outcomes included changes in serum creatinine, urea, potassium, and pH levels before and after treatment to evaluate efficacy. RESULTS: A total of 40 patients were included in each the low FF group and the high FF group. The baseline characteristics showed no statistically significant differences between the two groups (all P>0.05). All patients completed the treatment successfully, with a treatment duration of 10-12 hours, and no filter required replacement during the sessions. The differences in arterial pressure, venous pressure, and transmembrane pressure at 2 h, 6 h, and the end of treatment compared to values at 1 h showed no statistically significant differences between the two groups (all P>0.05). Furthermore, no significant difference was found in filter clotting grades (including Grade Ⅰ and Grade Ⅱ clotting) at the end of treatment between the two groups (all P>0.05). The creatinine clearance efficiency was significantly higher in the high FF group compared to the low FF group (P<0.01). However, no statistically significant differences were observed between the groups regarding urea reduction, or the changes in serum potassium and pH levels before and after treatment (all P>0.05). CONCLUSIONS For patients with a relatively short treatment duration of 10-12 h undergoing post-dilution CVVHDF, employing a FF of 25%-30% does not pose a higher risk of extracorporeal circuit coagulation compared to a FF of 20%-25%, but shows a trend towards higher creatinine clearance.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease lacking effective therapy. Metformin, an antidiabetic medication, has shown promising therapeutic properties in preclinical fibrosis models; however, its precise cellular targets and associated mechanisms in fibrosis resolution remain incompletely defined. Most research on metformin's effects has focused on mesenchymal and inflammatory responses with limited attention to epithelial cells. In this study, we utilized Sftpc lineage-traced and Fgfr2b conditional knockout mice, along with BMP2/PPARγ and AMPK inhibitors, to explore metformin's impact on alveolar epithelial cells in a bleomycin-induced pulmonary fibrosis model and cell culture. We found that metformin increased the proliferation and differentiation of alveolar type 2 (AT2) cells, particularly the recently identified injury-activated alveolar progenitors (IAAPs)-a subpopulation characterized by low SFTPC expression but enriched for PD-L1. Single-cell RNA sequencing revealed a reduction in apoptosis among mature AT2 cells. Interestingly, metformin's therapeutic effects were not significantly affected by BMP2 or PPARγ inhibition, which blocked the lipogenic differentiation of myofibroblasts. However, Fgfr2b deletion in Sftpc lineage cells significantly impaired metformin's ability to promote fibrosis resolution, a process linked to AMPK signaling. In conclusion, metformin alleviates fibrosis by directly activating AT2 cells, especially the IAAPs, through a mechanism that involves AMPK and FGFR2b signaling, but is largely independent of BMP2/PPARγ pathways.

OBJECTIVE To explore the effects of meropenem exposure and degradation levels on clinical efficacy in patients with purulent meningitis （PM）. METHODS A total of 131 PM patients treated with meropenem at the Affiliated Suzhou Hospital of Nanjing Medical University from January 2022 to June 2025 were prospectively included. Relevant data were collected and divided into a cured group （91 cases） and a non-cured group （40 cases） based on the efficacy. High-performance liquid chromatography-tandem mass spectrometry was used to determine the concentration of meropenem and its open-loop metabolites. Risk factors that affect efficacy were screened， and their predictive power and correlation were evaluated by univariate analysis， and multivariate Logistic regression analysis， receiver operating characteristic （ROC） curves， and correlation analysis. RESULTS Univariate analysis showed that serum creatinine， creatinine clearance rate， minimum inhibitory concentration of meropenem ≥16 μg/mL， cerebrospinal fluid red blood cell count， cerebrospinal fluid white blood cell count， cerebrospinal fluid glucose content， blood trough concentration， blood open-loop metabolite concentration/trough concentration ratio， and intrathecal injection were all correlated with efficacy （P＜0.05）. The results of multiple Logistic regression analysis showed that serum creatinine blood open-loop metabolite concentration/trough concentration ratio， intrathecal injection， and cerebrospinal fluid glucose content were influencing factors for suboptimal anti-infective ltt efficacy （P＜0.05）. ROC curve analysis showed that when the blood open-loop metabolite concentration/trough concentration ratio was greater than 2.854 （AUC＝0.647）， serum creatinine was less than 59.5 μmol/L （AUC＝0.647）， and cerebrospinal fluid glucose content was less than 3.37 mmol/L （AUC＝0.709）， the risk of treatment failure significantly increased （P＜0.05）. Correlation analysis showed that the blood trough concentration of meropenem was positively correlated with the concentration of its open-loop metabolites （R 2＝0.134 5， P＜0.000 1）. CONCLUSIONS Insufficient exposure level and rapid degradation of meropenem are key mechanisms affecting the anti-infective efficacy of PM. Elevated blood open-loop metabolite concentration/ trough concentration ratio， low serum creatinine level， lack of intrathecal injection， and low cerebrospinal fluid glucose content are independent risk factors for poor efficacy.

Objective:To discuss the clinical efficacy of recombinant human growth hormone(rhGH)in the treatment of the pediatric patients with growth hormone deficiency(GHD)and idiopathic short stature(ISS),and to clarify its clinical application value in the pediatric patients with short stature of different etiologies.Methods:The clinical data of 132 children with short stature who treated with rhGH from January 2018 to January 2023 were collected.They were divided into GHD group(n=70)and ISS group(n=62)based on different etiologies.The bone age,target height(TH),body mass index(BMI),height standard deviation score(HtSDS),changes in height standard deviation scores(ΔHtSDS)before treatment and 6 months after treatment,and growth velocity(GV)of the pediatric patients were calculated.Propensity score matching(PSM)and inverse probability of treatment weighting(IPTW)were used to balance the confounding factors between the pediatric patients in two groups and the efficacy and safety of the pediatric patients in two groups were evaluated.Results:There were significant differences in whether children were full-term,bone age,bone age maturity,and TH of the pediatric patients between two groups(P<0.05).Compared with before treatment,the height and HtSDS of the pediatric patients in both GHD and ISS groups were significantly increased after treated for 6 months(P<0.05).Before matched by PSM,there were significant differences in full-term,bone age,bone age maturity,and TH of the pediatric patients between two groups(P<0.05).After matched by PSM,there were no significant differences in gender,region,term birth status,mode of delivery,feeding method,age,bone age,height,BMI,TH,and pretreatment HtSDS of the pediatric patients between two groups(P>0.05);the standardized mean difference(SMD)differences of covariates except for region were<0.2.After weighted by IPTW,there were no significant differences in gender,region,term birth status,mode of delivery,feeding method,age,bone age,height,BMI,TH,and pretreatment HtSDS of the pediatric patients between two groups(P>0.05);all SMD of covariates except for term birth status were<0.2.Before balancing covariates,after meatched by PSM matching,and after weighted by IPTW weighting compared with GHD group,the GV and ΔHtSDS of the pediatric patients in ISS group were slightly increased,but the difference was not significant(P>0.05).In terms of adverse reactions,2 cases(2.68%)of fasting hyperglycemia and 7 cases(10.00%)of hypothyroidism occurred in GHD group;3 cases(4.84%)of fasting hyperglycemia and 2 cases(3.23%)of hypothyroidism occurred in ISS group.Conclusion:rhGH can promote the height increase in the patients with GHD and ISS,and there is no significant difference in the height-increasing efficacy between GHD and ISS children.The incidence of adverse reactions is relatively low during treatment,indicating good overall safety.

OBJECTIVE To evaluate the short-term efficacy of single-session microwave ablation for benign thyroid nodule.METHODS Patients with benign thyroid nodules treated by microwave ablation between June 2019 and December 2022 at the Department of Otolaryngology Head and Neck Surgery,the First Affiliated Hospital of Xi'an Jiaotong University,were included for analysis.Thyroid function was tested 1 month after treatment,and ultrasound and thyroid function were performed 3 months,6 months and 1 year after treatment.Volume reduction rates(VRR)of nodules were calculated.Data of the last follow-up within 1 year were included for analysis.Variables including gender,age,whether Hashimoto's thyroiditis was present,longitudinal diameter of nodules,solid volume of nodules were included for univariate and multivariate analysis.RESULTS A total of 151 patients with 163 nodules were included.The perioperative complication rate was 1.99%(3/151).The VRR at half year after treatment was(79.58±17.70)%,and the success rate at half year after treatment was 93.43%(128/137).The VRR of at 1year after treatment was(81.24±24.29)%.The 1-year treatment success rate was 92.77%(77/83).Univariate and multivariate analysis showed that nodular solid volume and age were independent factors affecting VRR after ablation.Regression coefficient of age and solid volume was 0.34(P<0.05)and-0.47(P<0.05),respectively.For every 1 cm3 increase in solid volume,1-year VRR(%)decreased by 0.47.Regression equation:1-year VRR=68.92+0.34×age-0.47×solid volume.Serum FT4 gradually decreased and the thyroid stimulating hormone(TSH)gradually increased within 6 months after ablation,and the differences were statistically significant(P<0.05).After 6 months,serum FT4 gradually recovered to the normal level and TSH gradually recovered.However,TSH still did not reach the preoperative level one year after ablation.FT3 decreased gradually after treatment,but there was no significant difference between the values at each time point(P=0.40).After the ablation of thyroid nodule,the mean value of thyroid function index fluctuated,but all of them were within the normal reference range.CONCLUSION Microwave ablation is a safe and effective treatment method for benign thyroid nodules,with an overall success rate of over 90%.Solid nodule volume and age are independent factors affecting the microwave ablation effect of benign thyroid nodules.

Objective To investigate the effect of adenotonsillectomy on immune function and sleep structure in children with obstructive sleep apnea-hypopnea syndrome(OSAHS).Methods A total of 94 children with OSAHS treated at Children's Hospital Affiliated to Zhengzhou University from November 2020 to June 2022 were selected as the observation group,and another 80 healthy children who underwent physical examinations at the same hospital during the same period were selected as the control group.Children in the observation group underwent bilateral tonsillectomy combined with endoscopic adenoidectomy.Changes in the sleep structure of children in the observation group were detected before surgery and at discharge by using a multi-channel sleep monitoring system.Venous blood samples were collected from children in the observation group before surgery,one month after surgery,and six months after surgery,while venous blood samples of children in the control group were collected on the day of physical examination.The serum levels of IgA,IgG and IgM were measured by using immunoturbidimetry,the percentages of CD3+,CD4+and CD8+in the plasma were measured by using flow cytometry,and the CD4+/CD8+ratio was calculated.Results Compared with before surgery,the proportion of non-rapid eye movement sleep(NREM)1,apnea-hypopnea index and obstructive apnea-hypopnea index of children in the observation group decreased at discharge,the proportions of NREM2,NREM3 and rapid eye movement sleep(REM),sleep efficiency and the lowest oxygen saturation increased,and REM time extended(P＜0.05).The preoperative serum levels of IgA,IgG and IgM in the observation group were significantly higher than those in the control group(P＜0.05).One month after surgery,the serum levels of IgA,IgG and IgM in the observation group were significantly lower than those in the control group(P＜0.05).There was no statistically significant difference in the serum levels of IgA,IgG and IgM between the observation group and the control group at six months after surgery(P＞0.05).One and six months after surgery,the serum levels of IgA,IgG and IgM in the observation group were significantly lower than those before surgery(P＜0.05),and the serum levels of IgA,IgG and IgM at six months after surgery were significantly higher than those one month after surgery(P＜0.05).The preoperative CD3+and CD4+percentages and the CD4+/CD8+ratio in the observation group were significantly lower than those in the control group,while the CD8+percentage was significantly higher than that in the control group(P＜0.05).One month after surgery,the CD3+and CD4+percentages and the CD4+/CD8+ratio in the observation group were significantly lower than those in the control group,while the CD8+percentage was significantly higher than that in the control group(P＜0.05).There was no statistically significant difference in the CD3+,CD4+and CD8+percentages and the CD4+/CD8+ratio between the observation group and the control group at six months after surgery(P＞0.05).One month after surgery,the CD3+and CD4+percentages and the CD4+/CD8+ratio in the observation group were significantly lower than those before surgery,while the CD8+percentage was significantly higher than that before surgery(P＜0.05);six months after surgery,the CD3+and CD4+percentages and the CD4+/CD8+ratio in the observation group were significantly higher than those before surgery,while the CD8+percentage was significantly lower than that before surgery(P＜0.05).The CD3+and CD4+percentages and the CD4+/CD8+ratio at six months after surgery were significantly higher than those at one month after surgery,while the CD8+percentage was significantly lower than that at one month after surgery in the observation group(P＜0.05).Conclusion Adenotonsillectomy can effectively prolong the REM time of OSAHS children and improve their sleep efficiency,sleep structure and the immune regulation function of the body.The immune function of the body decreases briefly after adenotonsillectomy,and then gradually returns to the normal level.

AIM:To investigate the effect of polycomb group ring finger 3(PCGF3)on the viability and apop-tosis of OSCC cells and its potential mechanism.METHODS:The data were downloaded from the online public database to predict the expression of PCGF3 in OSCC and its relationship with pathological stage survival rate.Fifty pairs of OSCC tissues and adjacent tissues were selected to analyze the relationship between the expression of PCGF3 and the survival rate of patients.The expression level of PCGF3 in the specimens was detected by IHC,and the extracted cancer and adja-cent tissues were homogenized to analyze its mRNA expression.The mRNA and protein expression levels of PCGF3 in the cells were analyzed by RT-qPCR and Western blot experiments,and the protein expressions of PCGF3,p-PI3K,p-AKT,cyclin D1 and cleaved caspase-3(cl-caspase-3)were further analyzed.In addition,the effects of PCGF3 on cell viability and apoptosis were also detected.Finally,subcutaneous tumor models in nude mice were constructed to verify the above experiments.RESULTS:PCGF3 was highly expressed in OSCC and was closely related to pathological stage,pathologi-cal grade,and survival rate of patients.PCGF3 was highly expressed in OSCC tissues and cell lines in the network online databases.Western blot results showed that the expressions of PCGF3,p-PI3K,p-AKT,cyclin D1 and cl-caspase-3 were decreased and increased respectively after knocking down or overexpressing PCGF3 in OSCC cells.And cell viability and apoptosis were affected.The volume and weight of tumors in sh-PCGF3 group were lower than those in sh-NC group,and HE results showed that the nuclear atypotype of tumor cells in sh-PCGF3 group was less than that in sh-NC group.CON-CLUSION:PCGF3 can significantly affect the viability and apoptosis of OSCC cells,and its potential mechanism is to ac-tivate the PI3K/AKT signaling pathway to participate in the proliferation and apoptosis of OSCC cells.

Objective:To summarize the best evidence for the management of fatigue-related symptom clusters in HIV/AIDS patients.Methods:According to the "6S" model, clinical decisions, guidelines, expert consensus, systematic reviews, Meta-analysis, evidence summary, and randomized controlled trials on the management of fatigue-related symptom clusters of HIV/AIDS patients were searched from top to bottom in BMJ Best Practice, UpToDate, Joanna Briggs Institute Evidence-Based Health Care Center Database, Agency for Healthcare Research and Quality, National Institute for Health and Clinical Excellence, Medlive, Joint United Nations Programme on HIV/AIDS, Cochrane Library, PubMed, Embase, China National Knowledge Infrastructure, WanFang data, China Biology Medicine disc and other databases and websites. The search period was from January 1, 2017, to July 30, 2023. Two researchers independently used corresponding quality evaluation tools to evaluate the methodological quality of the included literature. They extracted and summarized the best evidence for the management of fatigue-related symptom clusters in HIV/AIDS patients.Results:A total of 20 articles were included, including seven clinical decisions, three guidelines, two evidence summaries, one expert consensus, three systematic reviews, and four randomized controlled trials. Thirty-four pieces of evidence were summarized from four aspects: fatigue management, frailty management, sexual dysfunction management, and sleep disorder management.Conclusions:This study summarizes the best evidence for the management of fatigue-related symptom clusters in HIV/AIDS patients. Medical and nursing staff must select and apply the evidence in a targeted manner based on clinical situations.

Purpose: This study aims to evaluate the efficacy and safety of a new combination treatment of vinorelbine and pyrotinib in human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC) and provide higher level evidence for clinical practice. Materials and Methods: This was a prospective, single-arm, phase 2 trial conducted at three institutions in China. Patients with HER2-positive MBC, who had previously been treated with trastuzumab plus a taxane or trastuzumab plus pertuzumab combined with a chemotherapeutic agent, were enrolled between March 2020 and December 2021. All patients received pyrotinib 400 mg orally once daily plus vinorelbine 25 mg/m2 intravenously or 60-80 mg/m2 orally on day 1 and day 8 of 21-day cycle. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival, and safety. Results: A total of 39 patients were enrolled. All patients had been pretreated with trastuzumab and 23.1% (n=9) of them had accepted trastuzumab plus pertuzumab. The median follow-up time was 16.3 months (95% confidence interval [CI], 5.3 to 27.2), and the median PFS was 6.4 months (95% CI, 4.0 to 8.8). The ORR was 43.6% (95% CI, 27.8% to 60.4%) and the DCR was 84.6% (95% CI, 69.5% to 94.1%). The median PFS of patients with versus without prior pertuzumab treatment was 4.6 and 8.3 months (p=0.017). The most common grade 3/4 adverse events were diarrhea (28.2%), neutrophil count decreased (15.4%), white blood cell count decreased (7.7%), vomiting (5.1%), and anemia (2.6%). Conclusion Pyrotinib plus vinorelbine showed promising efficacy and tolerable toxicity as second-line treatment in patients with HER2-positive MBC.