To reduce the dependency on high-carbon-load chromatographic columns,a new method has been established for the determination of the content of docusate sodium using ion-pair high-performance liquid chromatography (IP-HPLC). Tetrapropylammonium chloride was used as the ion-pair reagent with a mobile phase, composition of acetonitrile:10 mmol/L tetrapropylammonium chloride solution = 66∶34, adjusting pH to 6.5 with 0.1% phosphoric acid solution,flow rate of 1.5 mL/min, detection wavelength of 214 nm,column temperature of 35 °C, and an injection volume of 25 μL,and quantified by an external standard method. The main peak of docusate sodium exhibited a tailing factor of 1.34. The method showed good linearity within the range of 0.02 mg/mL to 0.40 mg/mL, with a correlation coefficient (r) of 0.999 9. It also demonstrated good repeatability, with recovery ranging from 97.0% to 98.2% (n=6). The quantification limit was 3.31 μg/mL, and the detection limit was 2.76 μg/mL.In summary,the new method shows good durability, a wide linear range, and high sensitivity, it is suitable for the determination of docusate sodium.

Objective : To investigate the effects of branched-chain amino acid(BCAA) on the differentiation of 3T3-L1 preadipocytes and its potential mechanism. Methods : 3T3-L1 preadipocytes were divided into the Control, differentiation medium(DM), low-concentration BCAA, and high-concentration BCAA groups. A CCK-8 assay was utilized to evaluate pre-adipocyte survival under various BCAA concentrations. Oil-red O staining was used to observe the formation of lipid droplets in adipocytes. Intracellular triglyceride(TG) and total cholesterol(TC) were detected by enzymatic method. RT-qPCR and Western blot were used to detect the mRNA and protein expression of Stat3 and adipocyte differentiation-related genes. Results : CCK-8 results showed that the viability of 3T3-L1 cells was not affected when the BCAA concentration was ≤ 10 mmol/L. Compared with the DM group, the low-concentration BCAA groups(0.5 and 1.0 mmol/L) had significantly larger intracellular lipid droplets, increased number of lipid droplets, and elevated levels of the intracellular TC(0.88vs0.68 mmol/g; 0.83vs0.68 mmol/g,P<0.01) and TG(0.77vs0.40 mmol/g; 0.62vs0.40 mmol/g,P<0.01). Nevertheless, the cell differentiation in the high-concentration group(5.0 and 10.0 mmol/L) significantly decreased compared with that in the DM group. Further, levels of PPARγ, C/EBPα, Adiponectin, and FABP4 mRNA and protein expression significantly increased in the low-concentration group, but significantly decreased in the high-concentration group than that in the DM group(P<0.01). In addition, low concentrations of BCAA promoted stat3 phosphorylation, while high concentrations inhibited its phosphorylation(P<0.01). Conclusion BCAA have a dual role in regulating the differentiation of preadipocytes through Stat3, i.e. low concentrations of BCAA induce cell differentiation by promoting Stat3 phosphorylation; whereas high concentrations of BCAA inhibit Stat3 phosphorylation and cell differentiation.

Objective To investigate the value of first platelet count(PLT)to respiratory rate(RR)ratio(PLT/RR)on admission in the diagnosis and prognosis of secondary sepsis in pneumonia patients.Methods A total of 100 patients with pneumonia admitted to the First Affiliated Hospital of Army Medical University from May 2023 to August 2024 were selected as subjects.According to the presence or absence of pneumonia sepsis,they were divided into sepsis group(63 cases)and non-sepsis group(37 cases).The secondary sepsis in pneumonia pa-tients were followed up continuously for 30 d.According to the survival situation,they were divided into sur-vival group(54 cases)and death group(9 cases).PLT in peripheral blood was measured,vital signs were col-lected on the first day of admission,and PLT/RR was calculated.The receiver operating characteristic curve was used to evaluate the predictive value of PLT,RR and PLT/RR for secondary sepsis in pneumonia pa-tients.The systemic inflammatory response syndrome(SIRS)score,modified early warning score(MEWS)and quick sequential organ failure assessment(qSOFA)score on admission were calculated,and the clinical predictive value of SIRS score,MEWS and qSOFA score was compared.Results PLT and PLT/RR in sepsis group were lower than those in non-sepsis group(P<0.000 1),RR was higher than that in non-sepsis group(P<0.01).The area under the curve(AUC,95%CI)of PLT,RR and PLT/RR were 0.858(0.785-0.931),0.693(0.589-0.796)and 0.902(0.843-0.962),respectively.The optimal cut-off values were 146.5×109/L,20.5 per minute and 8.075,respectively.The specificity were 8.1%,83.8%and 2.7%,respec-tively.The sensitivity was 33.3%,50.8%and 30.2%,respectively.Compared with the non-sepsis group,the sepsis group had a significantly higher SIRS score(P<0.001),a significantly lower MEWS(P<0.000 1),and no significant difference in qSOFA score between the two groups(P>0.05).The AUC(95%CI)of SIRS score,MEWS and qSOFA score in predicting secondary sepsis in pneumonia patients were 0.717(0.616-0.818),0.748(0.650-0.846)and 0.505(0.389-0.622),respectively.The optimal cut-off values were 4.5,2.5 and 1.5 points,respectively.The specificity were 91.9%,2.7%and 100.0%,respectively.The sensitivity was 42.9%,33.3%and 6.3%,respectively.PLT and PLT/RR in death group were lower than those in sur-vival group(P<0.05),RR was higher than that in survival group(P<0.05).Secondary sepsis in pneumonia patients were followed up for 30 d,Kaplan-Meier survival curve showed that patients with PLT≤138.5×109/L had a lower 30 d survival rate(P=0.007 8).Patients with RR>24.5 per minute had a lower 30 d sur-vival rate(P=0.016 1).Patients with PLT/RR≤6.375 had a lower 30 d survival rate(P=0.002 3).Conclu-sion PLT/RR can be used as a biological index to predict secondary sepsis in pneumonia patients,which is better than SIRS score,MEWS and qSOFA score,and the prognosis of secondary sepsis in pneumonia patients with low PLT/RR is worse.

Objective To investigate the effect and mechanism of hypoxia inducible factor-1 α/aquaporin-4(HIF-1α/AQP4)pathway in high altitude cerebral edema(HACE)after blood-brain barrier injury in rats.Methods Adult male SD rats(n=40)were randomly divided into two groups:control group(Ctrl,n=20)and high altitude cerebral edema group(HACE,n=20).The rats in the control group were reared in Xining(altitude 2261 m)for 4 days,and the rats in HACE group were reared in low-pressure simulation chamber(altitude 5000 m)for 4 days.Brain water content was measured by the method of dry and wet weight.The intracranial structure,morphology and signal changes of small animals were observed through T2 weighted image of 7.0 T MRI.The morphological changes of neurons and the apoptosis of nerve cells in the CA1 region of hippocampal tissue were observed by the staining of Nissl and TUNEL.Immunohistochemical staining was performed to observe the extravasation of immunoglobulin G(IgG).The expressions of HIF-1α,AQP4,matrix metalloproteinase-9(MMP-9),claudin-5,occludin and zonula occludens-1(ZO-1)in the tissue of hippocampal were detected by the method of Western blotting and immunofluorescent staining.Results The brain water content increased significantly in the HACE group(P＜0.05).The neurons in CA1 region of hippocampal tissue were atrophic and deformed,the arrangement of neurons was disordered in the HACE group.The number of neurons decreased significantly,the apoptosis of nerve cells increased significantly,and the IgG exudates obviously in the CA1 region of hippocampal tissue in the HACE group.The expressions of HIF-1α,AQP4 and MMP-9 proteins increased significantly,while claudin-5,occludin and ZO-1 proteins decreased significantly in the CA1 region of hippocampal tissue,which detected by the method of Western blotting and immunofluorescent staining(P＜0.05).Conclusion Acute high-altitude hypoxia can induce to blood-brain barrier disruption through the HIF-1α/AQP4 pathway,resulting in high-altitude cerebral edema.

To reduce the dependency on high-carbon-load chromatographic columns,a new method has been established for the determination of the content of docusate sodium using ion-pair high-performance liquid chromatography(IP-HPLC).Tetrapropylammonium chloride was used as the ion-pair reagent with a mobile phase,composition of acetonitrile:10 mmol/L tetrapropylammonium chloride solution=66∶34,adjusting pH to 6.5 with 0.1%phosphoric acid solution,flow rate of 1.5 mL/min,detection wavelength of 214 nm,column temperature of 35℃,and an injection volume of 25 μL,and quantified by an external standard method.The main peak of docusate sodium exhibited a tailing factor of 1.34.The method showed good linearity within the range of 0.02 mg/mL to 0.40 mg/mL,with a correlation coefficient(r)of 0.999 9.It also demonstrated good repeatability,with recovery ranging from 97.0%to 98.2%(n=6).The quantification limit was 3.31 μg/mL,and the detection limit was 2.76 μg/mL.In summary,the new method shows good durability,a wide linear range,and high sensitivity,it is suitable for the determination of docusate sodium.

Objective:To explore the therapeutic effect of Banxia Baizhu Tianma Decoction on phlegm-dampness-blocking cervical vertigo and its influence on neck hemodynamics.Methods:96 patients with phlegm-dampness block type cervical vertigo admitted to our hospital from January 2022 to January 2024 were divided into control group and observation group,48 cases in each group.The control group was treated with conventional Western medicine,and the observation group was treated with Banxia Baizhu Tianma Decoction.Both groups were treated for 4 weeks and followed up for 6 months.The reduction time and disappearance time of vertigo were recorded.The score of cervical vertigo Symptom and Function Assessment Scale(ESCV)was performed before treatment and 1 day after treatment.The average blood flow level of basilar artery,right vertebral artery and left vertebral artery was detected,and the total clinical effective rate,recurrence rate and adverse reaction rate of the two groups were compared.Results:The reduction time and disappearance time of vertigo in the observation group were shorter than those in the control group(P＜0.05).Post-treatment,the ESCV score of both groups was higher than that before treatment;compared with the control group,the ESCV score of the observation group was higher post-treatment(P＜0.05).The total clinical effective rate of observation group was higher than that of control group,and the recurrence rate was lower than that of control group(P＜0.05).The hemodynamic index were higher after treatment than in the control group(P＜0.05).There was no difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion:Banxia Baizhu Tianma Decoction has certain curative effect on phlegm-dampness block type cervical vertigo,can effectively relieve vertigo symptoms,reduce recurrence,improve neck hemodynamics,and is safe,worthy of popularization and application.

Objective:To explore the therapeutic effect of Banxia Baizhu Tianma Decoction on phlegm-dampness-blocking cervical vertigo and its influence on neck hemodynamics.Methods:96 patients with phlegm-dampness block type cervical vertigo admitted to our hospital from January 2022 to January 2024 were divided into control group and observation group,48 cases in each group.The control group was treated with conventional Western medicine,and the observation group was treated with Banxia Baizhu Tianma Decoction.Both groups were treated for 4 weeks and followed up for 6 months.The reduction time and disappearance time of vertigo were recorded.The score of cervical vertigo Symptom and Function Assessment Scale(ESCV)was performed before treatment and 1 day after treatment.The average blood flow level of basilar artery,right vertebral artery and left vertebral artery was detected,and the total clinical effective rate,recurrence rate and adverse reaction rate of the two groups were compared.Results:The reduction time and disappearance time of vertigo in the observation group were shorter than those in the control group(P＜0.05).Post-treatment,the ESCV score of both groups was higher than that before treatment;compared with the control group,the ESCV score of the observation group was higher post-treatment(P＜0.05).The total clinical effective rate of observation group was higher than that of control group,and the recurrence rate was lower than that of control group(P＜0.05).The hemodynamic index were higher after treatment than in the control group(P＜0.05).There was no difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion:Banxia Baizhu Tianma Decoction has certain curative effect on phlegm-dampness block type cervical vertigo,can effectively relieve vertigo symptoms,reduce recurrence,improve neck hemodynamics,and is safe,worthy of popularization and application.

Objective:To investigate the expression of RNA binding protein ELAVL1 in prostate cancer(PCa),especially hor-mone-sensitive prostate cancer(HSPC),and its relationship with tumor proliferation.This study further aims to reveal the molecular mechanism by which ELAVL1 promotes HSPC proliferation by stabilizing SOX4 mRNA in an m6A-dependent manner.Methods:The expression of ELAVL1 in PCa tissues and its relationship with prognosis were analyzed in the Cancer Genome Atlas(TCGA)data-base,and the differences in HSPC and hormone-resistant prostate cancer(HRPC)were compared.And its relationship with prognosis were analyzed in the Cancer Genome Atlas(TCGA)database,and the differences in HSPC and hormone-resistant prostate cancer(HRPC)were compared.Western blot was used to detect ELAVL1 protein expression in PCa cell lines.After ELAVL1 knockdown by siRNA,cell proliferation was evaluated using CCK-8 assays,and changes in downstream target genes were detected by RT-qPCR.Tumor xenograft experiments in nude mice were performed to further assess the impact of ELAVL1 on tumor growth.The interaction be-tween ELAVL1 and SOX4 mRNA was verified by RIP-seq.And the mRNA and protein levels of SOX4 after knockdown of ELAVL1 were detected by RT-qPCR and Western blot,respectively.CCK-8 was used to evaluate the effect of SOX4 knockdown on cell prolifer-ation.MeRIP-qPCR was used to detect the m6A modification level of SOX4 and the effect of knocking down METTL3.RNA pull-down experiments verified the interaction between SOX4 RNA fragments and ELAVL1 protein.RNA stability experiments evaluated the effect of ELAVL1 knockdown on SOX4 mRNA stability.Results:The expression of ELAVL1 in PCa cells was higher than that in normal prostate epithelial cells.The prognosis of patients with high expression of ELAVL1 was significantly worse than that of patients with low expression.In the GSE32269 dataset,the expression level of ELAVL1 in HSPC was significantly higher than that in HRPC.After knocking down of ELAVL1 in LNCaP and VCaP cells,CCK-8 experiments showed that the cell proliferation ability was significantly af-fected after knocking down ELAVL1,and overexpressed ELAVL1 promoted the proliferation of HSPC cells.The results of in vivo studies showed that knockdown of ELAVL1 significantly inhibited the tumorigenic capacity of LNCaP cells and resulted in a marked reduction in xenograft tumor mass.The levels of SOX4 mRNA and protein in LNCaP and VCaP cells were significantly higher than those in nor-mal prostate epithelial cells RWPE-1.RIP-qPCR confirmed the interaction between ELAVL1 protein and SOX4 mRNA.After knocking down of ELAVL1,the expression levels of SOX4 mRNA and protein were significantly decreased.After knocking down of SOX4,the proliferation ability of LNCaP and VCaP cells was significantly inhibited.Conclusion:ELAVL1 is highly expressed in HSPC.High expression of ELAVL1 is associated with the proliferation of HSPC.SOX4 is a downstream molecule of ELAVL1 which promotes the proliferation of HSPC.ELAVL1 enhances the stability of SOX4 mRNA through an m6A-dependent mechanism.

Objective To investigate the efficacy of hypofractionated radiotherapy (HFRT) combined with programmed cell death protein-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors in sequential with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-2 (IL-2) for the treatment of advanced metastatic solid tumors. Methods A prospective single-center single-arm study was designed for patients failed standard treatments for advanced refractory solid tumors in the Department of Radiotherapy of Jiangyin Hospital affiliated to Nantong University, and eligible patients were given quadruple therapy: HFRT (5 to 8 Gy × 2 to 3 f) once every 21 days for at least 2 cycles; 200 μg GM-CSF from the 1st to 7th day of radiotherapy, and 2 million IU IL-2 from the 8thto 14th day. Within 1 week after the completion of HFRT, PD-1/PD-L1 inhibitors were used for treatment. The above treatment strategy was repeated. GM-CSF and IL-2 were treated for 6 cycles, followed by maintenance with PD-1/PD-L1 inhibitors until disease progression (PD) or intolerable toxicity occurred. Objective response rate (ORR) and treatment-related adverse events were analyzed. Results From January 9, 2021 to June 15, 2023, totally 40 patients were enrolled, with follow-up of 2.8 to 31.0 months and a median follow-up of 9.9 months, and 39 patients (97.5%) completed at least one time tumorsite evaluation within the non-radiotherapy target area. 97.5% of patients had cancers, 2.5% had soft tissue sarcomas, and 20.0% had received immune checkpoint inhibitors (ICIs) at baseline check. The ORR was 30.8%, and the disease control rate (DCR) was 71.8%; the ORR for non-small cell lung cancer (NSCLC) was 28.6%, and the DCR was 57.1%; the ORR for colorectal cancer was 14.3%, and the DCR was 71.4%; the ORR for gastric cancer was 16.7%, and the DCR was 66.7%; 28 patients (70.0%) had treatment-related adverse events (TRAE), 4 patients (10%) had TRAE≥level 3, and the most common types of TRAE were fatigue, fever and hypothyroidism. Conclusion The treatment of HFRT combined with immune checkpoint inhibitors in sequential with GM-CSF and IL-2 is well tolerated and toxicity accepted in patients with advanced metastatic solid tumors, which may provide a new method for salvage treatment of patients with advanced metastatic solid tumors.

Radiotherapy, as an important means of tumor treatment, plays a significant role in the treatment of cervical cancer. However, the ovaries are highly sensitive to radiation, which is prone to appear radiation-related injuries, leading to ovarian dysfunction and loss of fertility in young female patients, seriously affecting their physical and mental health. The degree of ovarian injury is influenced by various factors such as the dose, volume, and duration of radiation exposure to the ovaries, as well as the patient's age. Ovarian displacement and advancements in radiotherapy techniques can significantly relieve radiation-related ovarian injury. Currently, drug protection techniques are still immature, and new fertility preservation methods are receiving increasing attention but require further improvement. This article reviewed the research progress in the molecular mechanisms, prevention strategies, and new fertility preservation techniques for ovarian injury related to cervical cancer radiotherapy, aiming to provide a reference for ovarian function protection during radiotherapy for young cervical cancer patients.