Objective:To investigate the protective effect and its mechanism of proscillaridin A (PSD-A) on podocyte injury in lupus nephritis (LN).Methods:Molecular docking and surface plasmon resonance techniques were used to analyze the binding status of PSD-A to signal transducer and activator of transcription 1 (STAT1). The immortalized human podocyte injury model in the lupus group was induced by the serum of systemic lupus erythematosus patients, and the control and PSD-A intervention (2 nmol/L, 4 nmol/L) groups were also set up. Six female 12-week-old C57BL/6 mice were designated as the control group, and 12 female 12-week-old MRL/lpr lupus mice were randomly divided into lupus group and PSD-A intervention group by random number table method. The PSD-A intervention group was intraperitoneally injected with 5 mg/kg PSD-A, once per week for 6 consecutive weeks. While the control group and the lupus group were intraperitoneally injected with the same volume of the solvent without PSD-A. Western blotting and real-time quantitative PCR were employed to detect the relative protein and mRNA expression levels of podocin, STAT1, and interferon-induced protein with tetratricopeptide repeat 1 (IFIT1) in podocytes of each group. Enzyme-linked immunosorbent assay was used to detect the levels of serum anti-double strand DNA antibody and interferon-α in mice. Coomassie brilliant blue was used to detect the urinary protein level. HE, PAS, Masson and PASM staining and transmission electron microscopy were used to observe the pathological changes of renal tissues. Immunohistochemistry was used to examine the protein expression of podocin, STAT1 and IFIT1 in renal tissues.Results:Molecular docking and surface plasmon resonance techniques proved that PSD-A could bind to STAT1 protein and they exhibited a robust binding affinity. The podocyte experiments showed that, compared with the lupus group, the relative expression levels of podocin protein and mRNA in the PSD-A intervention group were upregulated, while the relative expression levels of STAT1 and IFIT1 protein and mRNA were downregulated (all P<0.05). The animal experiments showed that, compared with the lupus group, the serum levels of anti-double strand DNA antibody, interferon-α, and urinary protein in PSD-A intervention group were decreased, the pathological damage of renal tissues was alleviated, and the injury of renal podocytes was reduced. Immunohistochemical staining showed that the relative protein expression levels of STAT1 and IFIT1 of renal tissues in the PSD-A intervention group were lower than those in the lupus group (all P<0.05). Conclusion:PSD-A can play a protective role in podocyte injury in LN, and its mechanism may be related to the inhibition of the STAT1 signaling pathway.

Objective To investigate the effects of plateau hypoxia on the growth and tumor microenvironment of colorectal carcinoma in vivo.Methods A total of 16 male BALB/C mice(6 weeks old,weight 18-20 g)were randomly divided into plateau hypoxic group and plain normoxic group,with 8 mice in each group,while 14 male C57BL/6 mice were grouped in same way,with 7 mice in each group.The mice in the plateau hypoxic group were housed in a low-pressure oxygen(10%)chamber to simulate an altitude of approximately 5 600 m,while the mice of the other group was maintained in SPF-grade normal atmospheric conditions(21%oxygen,at an altitude of about 300 m).Colorectal tumor MC38 cells and colon adenocarcinoma CT26 cells were subcutaneously implanted into C57BL/6 mice and BALB/C mice,respectively to construct subcutaneous tumor-bearing mouse models.Then the tumor size and weight were measured in 4 groups of mice.After the tumor tissues,spleen and blood samples were collected in the C57BL/6 mice.Flow cytometry was used to determine the percentages of macrophages,T lymphocytes,IFN-γ+T lymphocytes,and myeloid-derived suppressor cells(MDSC).The differences in these immune cells were compared between the cells from the plateau hypoxic group and those from the plain normoxic group.Results The weight of subcutaneous tumor mass was significantly inhibited in both C57BL/6 and BALB/C mice from the plateau hypoxic group than those from the 2 plain normoxic groups(0.17 vs 0.09 g,1.38 vs 0.51 g,P<0.01).When compared with the immune cells from the tumor mass of the plain normoxic C57BL/6 mice,the percentage of M2-type macrophages was reduced in the tumor tissue from the plateau hypoxic mice(22.13%vs 15.90%,P<0.05),so was that of MDSC(2.06%vs 1.05%,P<0.01),particularly in the monocytic(M)-MDSC subgroup(60.97%vs 41.13%,P<0.01).While,no significant change was observed in the proportion of the polymorphonuclear(PMN)-MDSC subgroup(10.97%vs 9.70%,P>0.05).Additionally,the percentage of CD4+T cells was significantly reduced(48.70%vs 41.93%,P<0.05),whereas that of CD8+T cells was obviously increased(41.25%vs 51.18%,P<0.05),along with a notable rise in the proportions of IFN-γ+T,IFN-γ+CD4+T and IFN-γ+CD8+T cells(28.58%vs 59.65%,23.33%vs 53.65%,36.9%vs 66.48%,P<0.01).However,between the peripheral blood samples of the 2 groups of C57BL/6 mice,the proportions of M1-type macrophages and CD4+T cells were reduced(84.98%vs 78.43%,5.86%vs 4.01%,P<0.01),and those of MDSC and PMN-MDC were increased(4.47%vs 16.43%,36.56%vs 62.97%,P<0.01).In the spleen tissues,notable decreases were observed in the proportions of CD8+T cells and IFN-γ+CD8+T cells between the 2 groups(33.05%vs 27.68%,5.13%vs 1.58%,P<0.01).Conclusion Plateau hypoxia improves the immune response within the tumor microenvironment,and inhibits subcutaneous tumor growth of colorectal cancer,but suppresses systemic immune response.

Objective:To construct an evidence-based practice program for dietary management of patients with non-dialysis chronic kidney disease (CKD) based on best evidence and to evaluate the effectiveness of its application.Methods:The best evidence for dietary management of non-dialysis CKD patients was summarized. From September to October 2022, following the evidence clinical transformation model of the Fudan University Centre for Evidence-based Nursing, the best evidence was screened and evidence-based practice program were developed, taking into account patients' wishes, expert opinions, and clinical contexts. From November 2022 through March 2023, baseline reviews, analysis of barriers and facilitators were implemented. Between April 2023 and April 2024, evidence-based practice was carried out in the Department of Nephrology of the Second Affiliated Hospital of Guangzhou Medical University to compare the implementation rate of review indicators at the system, practitioner, and patient levels, and practitioners' knowledge before and after the application of evidence.Results:A total of 14 review indicators were developed. The implementation rate of the 12 review indicators and the practitioners' knowledge of the CKD diet were elevated after the evidence-based practice ( P<0.05) . Conclusions:Evidence-based practice program for dietary management of patients with non-dialysis CKD has a positive effect on improving practitioners' knowledge of non-dialysis CKD diets, implementation rate of dietary management behaviors, and patients' dietary behaviors.

Objective:To construct an evidence-based practice program for dietary management of patients with non-dialysis chronic kidney disease (CKD) based on best evidence and to evaluate the effectiveness of its application.Methods:The best evidence for dietary management of non-dialysis CKD patients was summarized. From September to October 2022, following the evidence clinical transformation model of the Fudan University Centre for Evidence-based Nursing, the best evidence was screened and evidence-based practice program were developed, taking into account patients' wishes, expert opinions, and clinical contexts. From November 2022 through March 2023, baseline reviews, analysis of barriers and facilitators were implemented. Between April 2023 and April 2024, evidence-based practice was carried out in the Department of Nephrology of the Second Affiliated Hospital of Guangzhou Medical University to compare the implementation rate of review indicators at the system, practitioner, and patient levels, and practitioners' knowledge before and after the application of evidence.Results:A total of 14 review indicators were developed. The implementation rate of the 12 review indicators and the practitioners' knowledge of the CKD diet were elevated after the evidence-based practice ( P<0.05) . Conclusions:Evidence-based practice program for dietary management of patients with non-dialysis CKD has a positive effect on improving practitioners' knowledge of non-dialysis CKD diets, implementation rate of dietary management behaviors, and patients' dietary behaviors.

Objective:To explore the differences in semen parameters and the embryo outcomes in assisted reproductive technology between infertile patients with different levels of polyzoospermia and normal sperm con-centration,focusing on the relationship between polyzoospermia and sperm nucleoprotein maturity.Methods:A total of 212 couples with polyzoospermia(concentration ≥ 125 × 106/ml)who were admitted to the Insititute of Women,Children and Reproductive Health for infertility from October 12,2020 to August 25,2022 were selected.According to the concentration range,108 couples were divided into polyzoospermia group A[concentration(125-＜250)× 106ml]and 104 couples were divided into polyzoospermia group B(concentration ≥250 × 106/ml).Another 119 infertile couples with normal sperm concentration[(20-80)× 106/ml]were selected as the control group.The difference of semen parameters among the 3 groups male patient was compared,and the cor-relation between sperm concentration and the proportion of nucleoprotein-immature sperm was analyzed.The em-bryo development and pregnancy outcomes were compared between the 3 groups of women who received in vitro fertilization using intracytoplasmic sperm injection(ICSI).Results:①The age,days of abstinence,sperm concen-tration,total number of motile spermatozoa,total number of spermatozoa,total number of progressive spermato-zoa,and proportion of nuclear protein immature spermatozoa were all higher in group A and group B male patient of polyspermia compared to the control group,while the semen volume was lower compared to the control group(P＜0.01).The results of correlation analysis showed a positive correlation between sperm concentration and the proportion of nuclear protein immature spermatozoa(r=0.240,P=0.000).②The rate of diprokaryotic fertilization(2PN)was reduced after assisted reproduction in group A and group B with polyzoospermia,among which the rate of polyzoospermia in group B was lower than that in control group(P＜0.05),and the clinical pregnancy rate was lower than that in control group(51.2％vs.69.3％),and the biochemical pregnancy rate was higher than that in control group(9.3％vs.1.3％,P＜0.05).Conclusions:The total number of progressive spermatozoa and motile spermatozoa was higher in polyzoospermia patients than control group,but the nuclear protein imma-ture of spermatozoa was significantly higher than that in control group.When the sperm concentration exceeded 125 × 106/ml,the 2PN rate decreased,and when the sperm concentration exceeded 250 × 106/ml,the clinical pregnancy rate decreased significantly.Interventions should be taken before the implementation of ART to reduce the negative effects of high sperm concentration.

Objective:To explore the differences in semen parameters and the embryo outcomes in assisted reproductive technology between infertile patients with different levels of polyzoospermia and normal sperm con-centration,focusing on the relationship between polyzoospermia and sperm nucleoprotein maturity.Methods:A total of 212 couples with polyzoospermia(concentration ≥ 125 × 106/ml)who were admitted to the Insititute of Women,Children and Reproductive Health for infertility from October 12,2020 to August 25,2022 were selected.According to the concentration range,108 couples were divided into polyzoospermia group A[concentration(125-＜250)× 106ml]and 104 couples were divided into polyzoospermia group B(concentration ≥250 × 106/ml).Another 119 infertile couples with normal sperm concentration[(20-80)× 106/ml]were selected as the control group.The difference of semen parameters among the 3 groups male patient was compared,and the cor-relation between sperm concentration and the proportion of nucleoprotein-immature sperm was analyzed.The em-bryo development and pregnancy outcomes were compared between the 3 groups of women who received in vitro fertilization using intracytoplasmic sperm injection(ICSI).Results:①The age,days of abstinence,sperm concen-tration,total number of motile spermatozoa,total number of spermatozoa,total number of progressive spermato-zoa,and proportion of nuclear protein immature spermatozoa were all higher in group A and group B male patient of polyspermia compared to the control group,while the semen volume was lower compared to the control group(P＜0.01).The results of correlation analysis showed a positive correlation between sperm concentration and the proportion of nuclear protein immature spermatozoa(r=0.240,P=0.000).②The rate of diprokaryotic fertilization(2PN)was reduced after assisted reproduction in group A and group B with polyzoospermia,among which the rate of polyzoospermia in group B was lower than that in control group(P＜0.05),and the clinical pregnancy rate was lower than that in control group(51.2％vs.69.3％),and the biochemical pregnancy rate was higher than that in control group(9.3％vs.1.3％,P＜0.05).Conclusions:The total number of progressive spermatozoa and motile spermatozoa was higher in polyzoospermia patients than control group,but the nuclear protein imma-ture of spermatozoa was significantly higher than that in control group.When the sperm concentration exceeded 125 × 106/ml,the 2PN rate decreased,and when the sperm concentration exceeded 250 × 106/ml,the clinical pregnancy rate decreased significantly.Interventions should be taken before the implementation of ART to reduce the negative effects of high sperm concentration.

Objective:To investigate the protective effect and its mechanism of proscillaridin A (PSD-A) on podocyte injury in lupus nephritis (LN).Methods:Molecular docking and surface plasmon resonance techniques were used to analyze the binding status of PSD-A to signal transducer and activator of transcription 1 (STAT1). The immortalized human podocyte injury model in the lupus group was induced by the serum of systemic lupus erythematosus patients, and the control and PSD-A intervention (2 nmol/L, 4 nmol/L) groups were also set up. Six female 12-week-old C57BL/6 mice were designated as the control group, and 12 female 12-week-old MRL/lpr lupus mice were randomly divided into lupus group and PSD-A intervention group by random number table method. The PSD-A intervention group was intraperitoneally injected with 5 mg/kg PSD-A, once per week for 6 consecutive weeks. While the control group and the lupus group were intraperitoneally injected with the same volume of the solvent without PSD-A. Western blotting and real-time quantitative PCR were employed to detect the relative protein and mRNA expression levels of podocin, STAT1, and interferon-induced protein with tetratricopeptide repeat 1 (IFIT1) in podocytes of each group. Enzyme-linked immunosorbent assay was used to detect the levels of serum anti-double strand DNA antibody and interferon-α in mice. Coomassie brilliant blue was used to detect the urinary protein level. HE, PAS, Masson and PASM staining and transmission electron microscopy were used to observe the pathological changes of renal tissues. Immunohistochemistry was used to examine the protein expression of podocin, STAT1 and IFIT1 in renal tissues.Results:Molecular docking and surface plasmon resonance techniques proved that PSD-A could bind to STAT1 protein and they exhibited a robust binding affinity. The podocyte experiments showed that, compared with the lupus group, the relative expression levels of podocin protein and mRNA in the PSD-A intervention group were upregulated, while the relative expression levels of STAT1 and IFIT1 protein and mRNA were downregulated (all P<0.05). The animal experiments showed that, compared with the lupus group, the serum levels of anti-double strand DNA antibody, interferon-α, and urinary protein in PSD-A intervention group were decreased, the pathological damage of renal tissues was alleviated, and the injury of renal podocytes was reduced. Immunohistochemical staining showed that the relative protein expression levels of STAT1 and IFIT1 of renal tissues in the PSD-A intervention group were lower than those in the lupus group (all P<0.05). Conclusion:PSD-A can play a protective role in podocyte injury in LN, and its mechanism may be related to the inhibition of the STAT1 signaling pathway.

During orthodontic treatment,irregular and varying sized nodular bony protrusions may sometimes appear on the labial side of the patient's anterior alveolar bone,which is closely related to the differential bone remodeling on the inner and outer surfaces of the alveolar bone.Labial protuberances not only affect the aesthetic results of orthodontic treatment,but also pose potential risks to periodontal health.Currently,it is believed that the influencing factors of the formation of the labial protuberances may be related to the patient's gender and age,tooth movement speed,and extent of anterior teeth retraction.Labial protuberances typically resolve spontaneously,however,if persistent,alveoloplasty may be necessary for treatment.This review provides a summary on the occurrence,influencing factors of formation,potential biological mechanisms,and corresponding treatment methods of labial protuberances during orthodontic treatment.

Objective To investigate whether the semen quality of men undergoing conventional semen analysis from this center has changed over time in 10 years.Methods The data of 231 519 semen samples provided by males undergoing conventional seminal anal-ysis in outpatient department of Reproductive Medicine Affiliated to Shandong University from January 2013 to December 2022 were ret-rospectively analyzed.The sperm concentration,motility,percentage of progressively motile sperm and percentage of normal morphology sperm were analyzed according to the World Health Organization(WHO)Laboratory Manual for the Examination and Treatment of Hu-man Semen(5th edition)and the changes of these parameters in 10 years were compared.Results From 2013 to 2022,there were no significant changes in the proportions of men with different sperm concentration,motility,percentage of progressively motile sperm in reproductive clinics.Approximately 27％of infertile male patients had low sperm concentration each year,approximately 34％of infer-tile male patients had low sperm motility each year,approximately 10％of infertile male patients was not found sperm in semen samples each year,and the percentages of normal morphology sperm of approximately 57％of infertile male patients were lower than the refer-ence value.The semen routine analysis results of approximately 50％of infertile male patients were in the normal range.The proportion of normal semen population did not change significantly.Conclusion The semen quality of infertile men does not change significantly in recent 10 years.

Objective:To investigate the development and influencing factors of frailty in elderly patients on maintenance hemodialysis.Methods:A cross-sectional survey involved 146 elderly patients on maintenance hemodialysis at the blood purification department of the First Affiliated Hospital of Xi'an Jiaotong University.A self-designed demographic questionnaire was used to collect general information of patients, the Simple Physical Performance Scale(SPPB)was used to assess physical function, the 5-item SARC-F was used as a tool for rapid screening of sarcopenia, and the Hospital Anxiety and Depression Scale(HADS)was used for screening of anxiety and depression.The FRAIL scale was used for frailty assessment and participants were divided into a no frailty group, a pre-frailty group and a frailty group according to different frailty scores.Relevant influencing factors of frailty were analyzed.Results:Among 146 hemodialysis patients, 33(22.6%)were in the non-frailty group, 86(58.9%)in the pre-frailty group, and 27(18.5%)in the frailty group.Univariate analysis showed that there were statistically significant differences in sex( χ2=6.220, P=0.045), age( F=5.197, P=0.007), body type( χ2=31.927, P<0.001), SARC-F score( χ2=24.283, P<0.001)and SPPB score( χ2=26.773, P<0.001)between different groups.There were 3 patients(9.4%)at high risk for sarcopenia in the no frailty group, 13 patients(40.6%)at high risk for sarcopenia in the pre-frailty group, and 16 patients(50%)at high risk for sarcopenia in the frailty group, and differences in the occurrence of sarcopenia between the different subgroups of frailty were statistically significant( χ2=27.496, P<0.001). Multifactorial Logistic regression analysis showed that age, ( OR=1.04, 95% CI: 0.99-1.08, P=0.049), sex( OR=0.39, 95% CI: 0.17-0.87, P=0.021), body size( OR=0.07, 95% CI: 0.01-0.50, P=0.008), SARC-F( OR=0.14, 95% CI: 0.05-0.38, P<0.001)were independent influencing factors of frailty in elderly maintenance hemodialysis patients( P<0.05). Conclusions:The incidence of frailty is high in elderly patients on maintenance hemodialysis, and the development of frailty is affected by age, body mass index and sarcopenia.