Objective:To explore the changes of aquaporin-4 (AQP4) expression in rat astrocytes (RA) and rat model of radiation-induced brain injury (RIBI) after X-ray radiation, as well as its impact on cell functions.Methods:Logarithmic-phase RA were divided into four groups: Sham group (no treatment), AQP4 siRNA group (transfected with AQP4 lentivirus), IR group (single 20 Gy X-ray irradiation), and IR+AQP4 siRNA group (transfected with AQP4 lentivirus followed by single 20 Gy X-ray irradiation). The cell proliferation viability after radiation was detected using the CCK-8 assay. The relative expression of AQP4 mRNA in each group was measured by quantitative reverse transcription polymerase chain reaction, and the optimal AQP4 siRNA lentiviral sequence was selected for further studies. Western blot was used to detect the relative expression levels of AQP4, phosphorylated histone H2A family member X (γH2AX), autophagy-related proteins, glial fibrillary acidic protein (GFAP), proteins in the phosphatidylinositol-3-kinase (PI3K) / protein kinase B (AKT) / mammalian target of rapamycin (mTOR) pathway, and apoptosis-related proteins in cells from each group. Immunofluorescence (co-expression) staining was used to detect the expression of AQP4, γH2AX, GFAP, LC3, phosphatase and tensin homolog-induced kinase 1 (PINK1) in cells from each group, as well as the expression of AQP4 and LC3 in brain tissues from the rat RIBI model. Flow cytometry was used to detect the apoptosis rate of cells in each group. The differences between two groups were compared using the t-test, while the differences among multiple groups were evaluated using analysis of variance (ANOVA) and Tukey's multiple comparison test. Results:The proliferation viability of RA decreased to its lowest level at 24 h after irradiation. At the 24 h post-irradiation time point, the expression levels of γH2AX and AQP4 were significantly increased in the IR group compared with the Sham group. The fluorescence intensity of AQP4 in the AQP4 siRNA group was lower than that in the Sham group. The cells in the IR group showed significant enlargement and irregular morphology, with a significant increase in AQP4 fluorescence intensity, while the IR+AQP4 siRNA group showed mild cell enlargement and lower AQP4 fluorescence intensity compared with the IR group. Compared with the Sham group, the expression of microtubule-associated protein1 light chain 3 (LC3) and PINK1 proteins were decreased in the IR group, while the IR+AQP4 siRNA group showed higher expression levels compared with the IR group. Compared with the Sham group, the IR group showed increased expression of AQP4, GFAP, and sequestosome 1 (P62) proteins, decreased expression of Beclin-1 (BECN1) and LC3 proteins, and a reduced LC3-II/LC3-I ratio, while the IR+AQP4 siRNA group exhibited a restored LC3-II/LC3-I ratio. The apoptosis rate in the AQP4 siRNA group was similar to that in the Sham group, while the IR group showed a significantly increased apoptosis rate, and the IR+AQP4 siRNA group had a lower apoptosis rate than the IR group. The expression of caspase-3 (Caspase3) decreased in the IR group, while the expression of PI3K, AKT, mTOR, extracellular signal-regulated kinase (ERK)1/2, and cleaved Caspase3 protein increased; these changes were partially reversed in the IR+AQP4 siRNA group. In the rat RIBI model, the expression area and intensity of AQP4 were higher in the IR group compared with the Sham group, while LC3 expression showed the opposite pattern.Conclusions:The possible molecular mechanism of RA apoptosis caused by X-ray irradiation is that irradiation promotes the expression of AQP4, causes cell swelling, inhibits autophagy, and prevents cells from clearing damaged organelles in a timely manner, thereby promoting cell apoptosis.

Objective To establish a risk prediction model of continuous renal replacement therapy(CRRT)withdrawal failure in patients with infectious shock complicating acute kidney injury(AKI)based on the decision tree algorithm,and to explore the influencing factors of CRRT withdrawal failure in patients with infectious shock complicating AKI.Methods 220 patients with infectious shock complicating AKI admitted to our hospital from May 2020 to May 2023 were retrospectively analyzed,and divided into success group and failure group according to the success or failure of the withdrawal,univariate and multivariate Logistic regression analysis were used to screen risk factors of CRRT withdrawal failure in patients with septic shock complicated with AKI,C-reactive protein/albumin(CRP/ALB)at admission and sepsis-related organ failure assessment(SOFA)score at withdrawal,acute physiology and chronic health evaluation(APACHE Ⅱ)score,N-terminal B-type natriuretic peptide(NT-proBNP)level at the beginning of CRRT,mean arterial pressure(MAP)grading,urine volume after withdrawal,and serum creatinine(Scr)level after withdrawal were taken into constructing a decision tree model and validating the model efficacy.Results In this study,there were 41.82％of patients failed to withdrawal.Combination of univariate and multivariate Logistic regression analysis showed that SOFA score at withdrawal,APACHE Ⅱ scores,urine volume after withdrawal,Scr level after withdrawal,NT-proBNP at the beginning of CRRT,and MAP grading,CRP/ALB at the time of admission were an independent risk factor for CRRT withdrawal failure in patients with septic shock complicated with AKI(P＜0.05).The results showed that the higher CRP/ALB was the most important influencing factor on the failure of CRRT evacuation in patients with infectious shock complicating AKI,and the area under the receiver operating characteristic curve was 0.965.Conclusion The decision tree model constructed by CRP/ALB at admission,SOFA score at withdrawal,urine volume after withdrawal,Scr level after withdrawal,APACHE Ⅱ score,and MAP grading has a better predictive efficacy of CRRT withdrawal failure in patients with infectious shock complicating AKI,which is a guideline for patients'prognostic assessment.

Objective To establish a risk prediction model of continuous renal replacement therapy(CRRT)withdrawal failure in patients with infectious shock complicating acute kidney injury(AKI)based on the decision tree algorithm,and to explore the influencing factors of CRRT withdrawal failure in patients with infectious shock complicating AKI.Methods 220 patients with infectious shock complicating AKI admitted to our hospital from May 2020 to May 2023 were retrospectively analyzed,and divided into success group and failure group according to the success or failure of the withdrawal,univariate and multivariate Logistic regression analysis were used to screen risk factors of CRRT withdrawal failure in patients with septic shock complicated with AKI,C-reactive protein/albumin(CRP/ALB)at admission and sepsis-related organ failure assessment(SOFA)score at withdrawal,acute physiology and chronic health evaluation(APACHE Ⅱ)score,N-terminal B-type natriuretic peptide(NT-proBNP)level at the beginning of CRRT,mean arterial pressure(MAP)grading,urine volume after withdrawal,and serum creatinine(Scr)level after withdrawal were taken into constructing a decision tree model and validating the model efficacy.Results In this study,there were 41.82％of patients failed to withdrawal.Combination of univariate and multivariate Logistic regression analysis showed that SOFA score at withdrawal,APACHE Ⅱ scores,urine volume after withdrawal,Scr level after withdrawal,NT-proBNP at the beginning of CRRT,and MAP grading,CRP/ALB at the time of admission were an independent risk factor for CRRT withdrawal failure in patients with septic shock complicated with AKI(P＜0.05).The results showed that the higher CRP/ALB was the most important influencing factor on the failure of CRRT evacuation in patients with infectious shock complicating AKI,and the area under the receiver operating characteristic curve was 0.965.Conclusion The decision tree model constructed by CRP/ALB at admission,SOFA score at withdrawal,urine volume after withdrawal,Scr level after withdrawal,APACHE Ⅱ score,and MAP grading has a better predictive efficacy of CRRT withdrawal failure in patients with infectious shock complicating AKI,which is a guideline for patients'prognostic assessment.

Objective To explore the effect of PCSK9 inhibitor combined with atorvastatin on carotid atherosclerosis and its anti-inflammatory effect in patients with hypertension complicated with type 2 diabetes mellitus.Methods A total of 100 patients with hypertension complicated with type 2 diabetes mellitus who were treated in Nanchang Third Hospital from October 2022 to August 2023 were selected as the research subjects.They were divided into the control group and the study group by the random number table method,with 50 cases in each group.Both groups of patients received conventional antihypertensive,hypoglycemic,and antiplatelet therapy.The control group took 20 mg of atorvastatin calcium tablets orally,once a night.On the basis of the control group,the study group was additionally given 150 mg of evolocumab injection(a PCSK9 inhibitor)by subcutaneous injection,once every two weeks.Both groups of patients were followed up for 24 weeks.The levels of blood lipids,blood glucose,inflammatory cytokines,carotid intima-media thickness(IMT),atherosclerotic plaque score and adverse reactions of the patients in the two groups before and after treatment were detected and compared.Results The levels of TC,TG and LDL-C in the study group after treatment were lower than those before treatment and those in the control group at the same period,and the differences were statistically significant(P＜0.05).The levels of IL-1,IL-6,TNF-α,hs-CRP,as well as the ca-rotid IMT and atherosclerotic plaque score in the study group after treatment were lower than those before treatment and those in the control group at the same period,and the differences were statistically significant(P＜O.05).During the treatment period,there was no significant difference in the occurrence of adverse reac-tions between the two groups(P＞0.05).Conclusion The combination of PCSK9 inhibitor and atorvastatin can effectively regulate the blood lipid levels of patients with hypertension complicated and type 2 diabetes mellitus,alleviate the inflammatory response,and improve the degree of carotid atherosclerosis in these pa-tients.

Aluminum adjuvants are widely used in the field of vaccines due to their ability to induce efficient and long-lasting immune responses and good safety profile. With the development of immunology, the requirements for adjuvants have gradually increased, and traditional aluminum adjuvants can no longer meet all the needs of application. The development of novel aluminum adjuvants has become a hot research topic in order to achieve good immunity-enhancing effects and induce specific types and strengths of immune responses. This review briefly introduces the mechanism of action and safety of aluminum adjuvants, with focus on the research progress of novel aluminum adjuvants in recent years, mainly including nano-aluminum adjuvants and composite aluminum adjuvants (aluminum adjuvants compounded with immunity-stimulating molecules or delivery carriers), and a prospect of their future research direction, aiming to provide some reference for the further development and clinical application of aluminum adjuvants.

Objective To explore causal relationship between 25-hydroxyvitamin D[25(OH)D]and ankylosing spondylitis(AS).Methods Genetic data of 25(OH)D and AS were extracted from the genome-wide association study.The causal effect of 25(OH)D on AS was estimated by MR-Egger regression method,weighted median,inverse variance weighted(IVW),simple mode and weighted mode,and sensitivity analysis was conducted for verification.Results The IVW results indicated that there was a causal relationship between 25(OH)D concentration and AS(OR=0.805,95％CI:0.686-0.944,P=0.008),and the maximum likelihood ratio(OR=0.799,95％CI:0.678-0.940,P=0.007)showed consistent results.The IVW results of the reverse Mendelian randomization study showed that there was no causal relationship between the two(OR=1.019,95％CI:0.995-1.043,P=0.110).In addition,MR-Egger intercept,Cochran Q test,"leave-one-out"and MR-PRESSO analysis showed no horizontal pleipotency or heterogeneity.Conclusion There may be a genetic causal relationship between the concentration of 25(OH)D and the onset of AS.AS cannot cause changes in the concentration of 25(OH)D in the body.

Objective To explore causal relationship between 25-hydroxyvitamin D[25(OH)D]and ankylosing spondylitis(AS).Methods Genetic data of 25(OH)D and AS were extracted from the genome-wide association study.The causal effect of 25(OH)D on AS was estimated by MR-Egger regression method,weighted median,inverse variance weighted(IVW),simple mode and weighted mode,and sensitivity analysis was conducted for verification.Results The IVW results indicated that there was a causal relationship between 25(OH)D concentration and AS(OR=0.805,95％CI:0.686-0.944,P=0.008),and the maximum likelihood ratio(OR=0.799,95％CI:0.678-0.940,P=0.007)showed consistent results.The IVW results of the reverse Mendelian randomization study showed that there was no causal relationship between the two(OR=1.019,95％CI:0.995-1.043,P=0.110).In addition,MR-Egger intercept,Cochran Q test,"leave-one-out"and MR-PRESSO analysis showed no horizontal pleipotency or heterogeneity.Conclusion There may be a genetic causal relationship between the concentration of 25(OH)D and the onset of AS.AS cannot cause changes in the concentration of 25(OH)D in the body.

Objective:To explore the changes of aquaporin-4 (AQP4) expression in rat astrocytes (RA) and rat model of radiation-induced brain injury (RIBI) after X-ray radiation, as well as its impact on cell functions.Methods:Logarithmic-phase RA were divided into four groups: Sham group (no treatment), AQP4 siRNA group (transfected with AQP4 lentivirus), IR group (single 20 Gy X-ray irradiation), and IR+AQP4 siRNA group (transfected with AQP4 lentivirus followed by single 20 Gy X-ray irradiation). The cell proliferation viability after radiation was detected using the CCK-8 assay. The relative expression of AQP4 mRNA in each group was measured by quantitative reverse transcription polymerase chain reaction, and the optimal AQP4 siRNA lentiviral sequence was selected for further studies. Western blot was used to detect the relative expression levels of AQP4, phosphorylated histone H2A family member X (γH2AX), autophagy-related proteins, glial fibrillary acidic protein (GFAP), proteins in the phosphatidylinositol-3-kinase (PI3K) / protein kinase B (AKT) / mammalian target of rapamycin (mTOR) pathway, and apoptosis-related proteins in cells from each group. Immunofluorescence (co-expression) staining was used to detect the expression of AQP4, γH2AX, GFAP, LC3, phosphatase and tensin homolog-induced kinase 1 (PINK1) in cells from each group, as well as the expression of AQP4 and LC3 in brain tissues from the rat RIBI model. Flow cytometry was used to detect the apoptosis rate of cells in each group. The differences between two groups were compared using the t-test, while the differences among multiple groups were evaluated using analysis of variance (ANOVA) and Tukey's multiple comparison test. Results:The proliferation viability of RA decreased to its lowest level at 24 h after irradiation. At the 24 h post-irradiation time point, the expression levels of γH2AX and AQP4 were significantly increased in the IR group compared with the Sham group. The fluorescence intensity of AQP4 in the AQP4 siRNA group was lower than that in the Sham group. The cells in the IR group showed significant enlargement and irregular morphology, with a significant increase in AQP4 fluorescence intensity, while the IR+AQP4 siRNA group showed mild cell enlargement and lower AQP4 fluorescence intensity compared with the IR group. Compared with the Sham group, the expression of microtubule-associated protein1 light chain 3 (LC3) and PINK1 proteins were decreased in the IR group, while the IR+AQP4 siRNA group showed higher expression levels compared with the IR group. Compared with the Sham group, the IR group showed increased expression of AQP4, GFAP, and sequestosome 1 (P62) proteins, decreased expression of Beclin-1 (BECN1) and LC3 proteins, and a reduced LC3-II/LC3-I ratio, while the IR+AQP4 siRNA group exhibited a restored LC3-II/LC3-I ratio. The apoptosis rate in the AQP4 siRNA group was similar to that in the Sham group, while the IR group showed a significantly increased apoptosis rate, and the IR+AQP4 siRNA group had a lower apoptosis rate than the IR group. The expression of caspase-3 (Caspase3) decreased in the IR group, while the expression of PI3K, AKT, mTOR, extracellular signal-regulated kinase (ERK)1/2, and cleaved Caspase3 protein increased; these changes were partially reversed in the IR+AQP4 siRNA group. In the rat RIBI model, the expression area and intensity of AQP4 were higher in the IR group compared with the Sham group, while LC3 expression showed the opposite pattern.Conclusions:The possible molecular mechanism of RA apoptosis caused by X-ray irradiation is that irradiation promotes the expression of AQP4, causes cell swelling, inhibits autophagy, and prevents cells from clearing damaged organelles in a timely manner, thereby promoting cell apoptosis.

Objective To observe the clinical efficacy and safety of secukinumab injection combined with acitretin capsules in the treatment of patients with moderate to severe plaque psoriasis.Methods Patients with moderate to severe plaque psoriasis were randomized into control group and treatment group.The control group received acitretin capsules 30 mg per time,qd,orally,after 4 weeks of maintenance therapy,the dose was reduced to 10-20 mg·d-1 and continued for 12 weeks.On the basis treatment of control group,the treatment group received secukinumab injection 300 mg per time,subcutaneous injection,once a week,after 4 weeks of maintenance treatment,it was adjusted to once every 4 weeks and continued treatment for 12 weeks.The clinical efficacy,serum inflammatory factors,humoral immune indicators and safety were compared between the two groups.Results Fifty-three patients were enrolled in the treatment group,with one dropout,and 52 patients were finally included in the statistical analysis;fifty-two patients were enrolled in the control group,with two dropouts,and 50 patients were finally included in the statistical analysis.After treatment,the total effective rates of treatment and control groups were 80.77％(42 cases/52 cases)and 62.00％(31 cases/50 cases),and the difference was statistically significant(P＜0.05).After treatment,the interleukin(IL)-17 levels of treatment and control groups were(21.06±3.14)and(23.82±3.51)ng·L-1;the IL-23 levels were(97.15±20.21)and(121.17±21.63)ng·L-1;the tumor necrosis factor-α levels were(33.65±5.71)and(37.53±7.64)ng·mL-1;the ratios of neutrophil count to lymphocyte count were 2.04±0.25 and 2.16±0.29;the mmunoglobulin(Ig)A levels were(2.34±0.32)and(2.51±0.38)g·L-1;the IgG levels were(11.51±2.16)and(12.79±2.41)g·L-1;the IgM levels were(1.02±0.26)and(0.91±0.25)g·L-1;the neutrophil counts were(5.19±1.12)× 109 and(4.32±0.94)× 109·L-1;the lymphocyte counts were(2.33±0.34)× 109 and(2.29±0.31)× 109·L-1;the PASI scores were(7.51±2.03)and(11.29±2.65)points;the DLQI scores were(7.04±1.26)and(9.23±2.51)points,respectively.The differences of above indexes were statistically significant between the treatment group and control group(all P＜0.05).The adverse drug reactions of treatment group were dry eyes,elevated transaminase,rhinitis/bronchitis,pruritus and gastrointestinal reactions,while those in control group were dry eyes,elevated transaminases,gastrointestinal reaction and elevated triacylglycerol.The incidences of total drug adverse reactions in the treatment and control groups were 17.31％and 16.00％,without significant difference(P＞0.05).Conclusion The clinical efficacy of secukinumab injection combined with acitretin capsules in the treatment of patients with moderate to severe plaque psoriasis is better than acitretin capsules alone,which can inhibit inflammation,improve immune function,reduce PASI and DLQI scores,without increasing the incidence of adverse drug reactions.

Objective To evaluate the effect of acupuncture at Yin Wei point on postoperative nausea and vomiting(PONV)in female patients undergoing abdominal surgery.The clinical efficacy of postoperative nausea and vomiting(PONV)and its impact on gut microbiota.Methods This study included 184 patients who underwent gynecological laparoscopic surgery in Jinhua Central Hospital from January 2021 to April 2024.They were randomly divided into control group(n=93)and acupuncture group(n=91)using a random number method.At the completion of surgery,the control group received intravenous injection of 5mg of tropisetron hydrochloride.In acupuncture group,on the basis of control group,intervention was performed by needling the palmar Yin Wei points of both forearms for 30 minutes before surgery.The incidence and severity of PONV were compared between two groups of patients.In addition,fecal samples were collected from two groups of patients before and after surgery,and differential analysis of gut microbiota community structure was performed using 16S amplicon absolute quantitative sequencing technology.Results In the 0-24 hours after surgery,40 cases of the acupuncture group and 56 cases of control group experienced PONV.The acupuncture group's PONV incidence was lower than control group's(P＜0.05).The nausea severity of acupuncture group after surgery was significantly lower than that of control groups.The proportion of patients taking antiemetic drugs after surgery in acupuncture group was also significantly lower than that in control group(P＜0.05).Before surgery,the two groups have no significant difference regarding Chao1,ACE,Shannon,and Simpson indices(P＞0.05).After surgery,the acupuncture group's Chao1,ACE,and Shannon indices were significantly higher than control group's(P＜0.05).The Simpson scores of two groups of patients were compared after surgery,and no significant difference was found(P＞0.05).The Observed,Chao1,ACE,and Shannon indices were significantly higher in the acupuncture group after surgery than before(P＜0.05).The incidence of adverse reactions in acupuncture group and control group were 8.8％and 8.6％,respectively,and there was no statistical significance(P＞0.05).Conclusion Acupuncture at Yin Wei point combined with intravenous injection of tropisetron can reduce the incidence of PONV in patients undergoing gynecological laparoscopic surgery.