OBJECTIVE:Neuromuscular exercise is a new comprehensive rehabilitation therapy in recent years,but its effect on knee osteoarthritis is still controversial.The purpose of this paper is to systematically evaluate the efficacy of neuromuscular exercise on knee osteoarthritis pain and function. METHODS:The randomized controlled trials addressing neuromuscular exercise in the treatment of knee osteoarthritis pain and function were retrieved from PubMed,Cochrane Library,Embase,EBSCO,CNKI,Web of Science,China Biomedical Database(CBM),VIP,and WanFang Database.The retrieval time ranged from database inception to October 2023.The neuromuscular training group(experimental group)was given neuromuscular training or neuromuscular training as the main intervention;the control group was a blank group or given conventional rehabilitation.Outcome indicators included the Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)score,walking time,knee stability,and the maximum number of knee flexion in 30 seconds.The risk of bias was evaluated by the Cochrane Collaboration tool and the Physiotherapy Evidence Database.Meta-analysis was performed using RevMan 5.4 software. RESULTS:A total of 11 randomized controlled trials were included,and 628 samples were extracted.The results of Meta-analysis showed that the experimental group was superior to the control group in terms of WOMAC pain score[standardized mean difference(SMD)=0.38,95%confidence interval(CI):0.08-0.69,P=0.01],knee stability(SMD=0.57,95%CI:0.23-0.92,P=0.001),the maximum number of knee joint flexion in 30 seconds(SMD=0.35,95%CI:0.05-0.65,P=0.02),and WOMAC physical function score(SMD=-0.79,95%CI:-1.30 to-0.28,P=0.002).In both groups,walking speed was increased and walking ability was improved in patients with knee osteoarthritis,but there was no significant difference(walking time:SMD=-0.22,95%CI:-0.48-0.03,P=0.09). CONCLUSION:Neuromuscular exercise can effectively improve knee joint pain,enhance the stability of the knee joint,and promote functional recovery in patients with knee osteoarthritis.However,more high-quality randomized controlled trials are still needed to further confirm the research.

Objective To analyze the detrimental effects of exposure to environmental noise alone and combined with carbon monoxide(CO)on spermatogenesis in male rats,investigate the underlying mechanisms involved in such damage,and evaluate the protective role of pterostilbene(PTE)against these adverse effects.Methods Sixty male SD rats(6～8 weeks old,weighing 200±10 g)were randomly divided normal control group(standard housing),sham-exposure control group(restraint stress only),noise exposure(85 dB),CO exposure(460 mg/m3),combined exposure(simultaneous exposure),and PTE intervention(80 mg/kg pretreatment),with 10 animals in each group.The rats were exposed daily for 2 h via a nose-only inhalation exposure system within a multifactorial environmental simulation chamber for 60 consecutive days.Sperm count and viability were measured after exposure.Histopathological changes of testicular tissues were observed with HE staining.qRT-PCR was used to measure stage-specific mRNA levels in germ cells.Serum sex hormone levels and adenosine triphosphate(ATP)concentrations in testes and sperm were detected.Transmission electron microscopy(TEM)was applied to observe the ultrastructural damage in the spermatocytes.Additionally,transcriptome sequencing was performed on testicular tissue,followed by bioinformatics analysis.Results Compared with the negative control group,the combined exposure group exhibited significant reductions in sperm viability and count(P<0.05),and developmental arrest of immature germ cells in the testicular tissue,with obviously less spermatogonia,spermatocytes,and round/elongated spermatids(P<0.01).Additionally,significantly reduced levels of reproductive-related hormones,such as gonadotropin-releasing hormone,follicle-stimulating hormone,luteinizing hormone and testosterone,and ATP levels in testes and sperm were observed in the mice after combined exposure(P<0.01),accompanied by mitochondrial rupture and cristae disruption in spermatocytes.Conversely,the PTE intervention group showed marked alleviation of these impairments,with parameters recovering almost to normal levels.Transcriptome sequencing identified biological processes related to reproductive development and ATP-dependent pathways as potential contributors to testicular injury induced by noise and CO exposure,with key genes including Nppa,Adm,Gnrh1,Ptafr,Atp13a5,Atp8b1,and LOC102555469.Conclusion Noise and CO exposure induce spermatogenic damage in rats,which may be related with energy metabolism and hormonal regulation,while PTE demonstrates significant protective effects against such reproductive impairments.

BACKGROUND:Eupatilin,a flavonoid active component derived from Artemisia sinensis,has been reported to relieve inflammation and improve neurological scores in rats with subarachnoid hemorrhage,but its role and mechanism in learning and memory remain unclear.OBJECTIVE:To investigate the effects of eupatilin on learning and memory abilities and P38 mitogen activated protein kinase(p38 MAPK)/signal transducer and activator of transcription-3(STAT3)pathway proteins in rats with subarachnoid hemorrhage.METHODS:A total of 50 Sprague-Dawley rats were randomly divided into sham surgery group,model group,eupatilin group,hesperetin group,eupatilin+hesperetin group,with 10 rats in each group.Except for the sham surgery group,the rats in the other groups were used to construct a subarachnoid hemorrhage model through intravascular perforation.Two hours after successful modeling,the eupatilin group was injected with 10 mg/kg eupatilin via the tail vein,the hesperetin group was injected with 50 mg/kg hesperetin(p38 MAPK/STAT3 signaling pathway activator)via the tail vein,the eupatilin+hesperetin group was injected with 10 mg/kg eupatilin and 50 mg/kg hesperetin via the tail vein,and the sham surgery group and the model group were injected with 10 mL/kg saline via the tail vein.The drug treatment lasted for 24 hours.The neurologic deficit score and Morris water maze experiment were applied to detect the neurological function and learning and memory abilities of rats.Hematoxylin-eosin staining was performed to detect the histopathological changes of the hippocampus.TUNEL method was used to detect neuronal apoptosis.Immunohistochemical staining was conducted to detect the number of doublecortin-positive cells in hippocampal tissue.Western blot was applied to detect the expression of p38 MAPK/STAT3 protein in hippocampal tissue.RESULTS AND CONCLUSION:Compared with the sham surgery group,rats in the model group had lower neurological deficit scores,learning and memory abilities,and number of doublecortin-positive cells(P<0.05),and higher neuronal apoptosis rate and protein expression of p-p38 MAPK/p38 MAPK and p-STAT3/STAT3(P<0.05).Compared with the model group,rats in the eupatilin group showed higher neurological deficit scores,learning and memory abilities,and number of doublecortin-positive cells(P<0.05),and lower neuronal apoptosis rate and protein expression of p-p38 MAPK/p38 MAPK and p-STAT3/STAT3(P<0.05),while those in the nerolone group showed lower neurological deficit scores,learning and memory abilities,and number of doublecortin-positive cells(P<0.05),and higher neuronal apoptosis rate and protein expression of p-p38 MAPK/p38 MAPK and p-STAT3/STAT3(P<0.05).Compared with the eupatilin group,rats in the eupatilin+hesperetin group had lower neurological deficit scores,learning memory abilities,and number of doublecortin-positive cells(P<0.05),and higher neuronal apoptosis rate and protein expression of p-p38 MAPK/p38 MAPK and p-STAT3/STAT3(P<0.05).Hematoxylin-eosin staining showed that compared with the model group,the nerve cells were more neatly arranged in the eupatilin group,disorganized in the hesperetin group,and arranged in a similar way to the model group in the eupatilin+hesperetin group.To conclude,eupatilin may improve learning and memory abilities of rats with subarachnoid hemorrhage by inhibiting the p38 MAPK/STAT3 signaling pathway.

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.

BACKGROUND:Eupatilin,a flavonoid active component derived from Artemisia sinensis,has been reported to relieve inflammation and improve neurological scores in rats with subarachnoid hemorrhage,but its role and mechanism in learning and memory remain unclear.OBJECTIVE:To investigate the effects of eupatilin on learning and memory abilities and P38 mitogen activated protein kinase(p38 MAPK)/signal transducer and activator of transcription-3(STAT3)pathway proteins in rats with subarachnoid hemorrhage.METHODS:A total of 50 Sprague-Dawley rats were randomly divided into sham surgery group,model group,eupatilin group,hesperetin group,eupatilin+hesperetin group,with 10 rats in each group.Except for the sham surgery group,the rats in the other groups were used to construct a subarachnoid hemorrhage model through intravascular perforation.Two hours after successful modeling,the eupatilin group was injected with 10 mg/kg eupatilin via the tail vein,the hesperetin group was injected with 50 mg/kg hesperetin(p38 MAPK/STAT3 signaling pathway activator)via the tail vein,the eupatilin+hesperetin group was injected with 10 mg/kg eupatilin and 50 mg/kg hesperetin via the tail vein,and the sham surgery group and the model group were injected with 10 mL/kg saline via the tail vein.The drug treatment lasted for 24 hours.The neurologic deficit score and Morris water maze experiment were applied to detect the neurological function and learning and memory abilities of rats.Hematoxylin-eosin staining was performed to detect the histopathological changes of the hippocampus.TUNEL method was used to detect neuronal apoptosis.Immunohistochemical staining was conducted to detect the number of doublecortin-positive cells in hippocampal tissue.Western blot was applied to detect the expression of p38 MAPK/STAT3 protein in hippocampal tissue.RESULTS AND CONCLUSION:Compared with the sham surgery group,rats in the model group had lower neurological deficit scores,learning and memory abilities,and number of doublecortin-positive cells(P<0.05),and higher neuronal apoptosis rate and protein expression of p-p38 MAPK/p38 MAPK and p-STAT3/STAT3(P<0.05).Compared with the model group,rats in the eupatilin group showed higher neurological deficit scores,learning and memory abilities,and number of doublecortin-positive cells(P<0.05),and lower neuronal apoptosis rate and protein expression of p-p38 MAPK/p38 MAPK and p-STAT3/STAT3(P<0.05),while those in the nerolone group showed lower neurological deficit scores,learning and memory abilities,and number of doublecortin-positive cells(P<0.05),and higher neuronal apoptosis rate and protein expression of p-p38 MAPK/p38 MAPK and p-STAT3/STAT3(P<0.05).Compared with the eupatilin group,rats in the eupatilin+hesperetin group had lower neurological deficit scores,learning memory abilities,and number of doublecortin-positive cells(P<0.05),and higher neuronal apoptosis rate and protein expression of p-p38 MAPK/p38 MAPK and p-STAT3/STAT3(P<0.05).Hematoxylin-eosin staining showed that compared with the model group,the nerve cells were more neatly arranged in the eupatilin group,disorganized in the hesperetin group,and arranged in a similar way to the model group in the eupatilin+hesperetin group.To conclude,eupatilin may improve learning and memory abilities of rats with subarachnoid hemorrhage by inhibiting the p38 MAPK/STAT3 signaling pathway.

Objective:To investigate the effect of long non-coding RNA (lncRNA) H19 regulating miRNA-675 (miR-675) and phosphatase and tensin homologue-deleted chromosome ten gene (PTEN) on the cell proliferation of glioma.Methods:Glioma cell lines U87-MG and U251 were chosen. The siRNA online design tool wad used to design small interfering RNA (siRNA) targeting H19. U87-MG and U251 cell lines with the stable knockdown of H19 were constructed (the stable knockdown of H19 group), and the cells randomly transfected with siRNA plasmid were taken as the control group, and normal cultured cells were treated as the blank group. Additionally, miR-675 and control microRNA were transfected into U87-MG and U251 with the stable knockdown of H19 (the overexpressing miR-675 group and the corresponding control group). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the relative expression levels of miR-675 and H19 in each group; the methyl thiazolyl tetrazolium (MTT) assay was used to detect the cell proliferation ability; the dual luciferase reporter gene assay was used to verify the targeting relationship between miR-675 and PTEN; Western blot was used to detect the relative expression level of PTEN protein.Results:The MTT assay results showed that the proliferation ability of U87-MG and U251 cells in the stable knockdown of H19 group was lower than that of the corresponding control group; and the differences in cell proliferation ability of all the groups after 48 h of culture were statistically significant (all P < 0.05). qRT-PCR detection results showed that the relative expression level of miR-675 in U251 cells in the stable knockdown of H19 group and the corresponding control group was 0.329±0.009 and 1.043±0.087, respectively, and the difference was statistically significant ( t = 14.15, P < 0.001); the relative expression level of miR-675 in U87-MG cells in the stable knockdown of H19 group and the corresponding control group was 0.299±0.009 and 1.027±0.106, respectively, and the difference was statistically significant ( t = 11.85, P < 0.001); the relative expression level of miR-675 in U87-MG and U251 cells in the stable knockdown of H19 group was lower than that of the corresponding control group. The dual luciferase reporter gene assay verified that miR-675 could bind to the 3'-UTR of PTEN. Western blot detection results showed that the relative expression level of PTEN protein in U87-MG and U251 cells in the stable knockdown of H19 group was higher than that of the corresponding control group and the blank group; in the U87-MG and U251 cells in the stable knockdown of H19 group, the relative expression level of PTEN in the overexpressing miR-675 group was lower than that of the corresponding blank group and the control group. In the U87-MG and U251 cells in the stable knockdown of H19 group, the cell proliferation ability of the overexpressing miR-675 group was higher than that of the corresponding blank group and the control group; the differences in cell proliferation ability of all the groups after 48 h of culture were statistically significant (all P < 0.05). Conclusions:lncRNA H19 may regulate the cell proliferation of glioma cells through the miR-675-PTEN signaling pathway.

OBJECTIVE:At present,there are a variety of treatment methods for scoliosis using specific exercise therapy,but there is a lack of comparison of efficacy between different specific exercise therapy.This article compared the effectiveness of different specific exercise therapies to treat adolescent idiopathic scoliosis through a network meta-analysis. METHODS:Domestic and foreign electronic databases of relevant studies were searched for randomized controlled trials of specific exercise therapy for adolescent idiopathic scoliosis.Search time was from January 2000 to July 2023.The literature was screened by two reviewers using RevMan 5.4 and Stata 16.0 software to extract data and assess the bias risk of of inclusion studies. RESULTS:(1)This article includes 20 randomized controlled trials with 1 377 patients.Of them,12 studies involved Schroth therapy;2 studies involved BSPTS therapy,and 6 studies involved SEAS therapy.(2)The network meta-analysis indicated that in terms of improving Cobb angle and reducing trunk rotation angle in scoliosis patients,the BSPTS therapy group and Schroth therapy group were better than the conventional control group[WMD=-4.60,95%CI(-8.37,-0.82),P<0.05;WMD=-3.37,95%CI(-4.98,-1.75),P<0.05;WMD=-3.20,95%CI(-5.50,-0.90),P<0.05;WMD=-2.13,95%CI(-3.16,-1.09),P<0.05].The Schroth therapy group performed better than the conventional control group effective in improving the International Society for Scoliosis Research-22 Questionnaire quality of life score[WMD=1.41,95%CI(0.07,2.75),P<0.05]. CONCLUSION:Given the current evidence,BSPTS therapy group and Schroth therapy group were better than the conventional control group in improving Cobb angle and reducing trunk rotation angle.In the comparison of different specific exercise therapies,BSPTS therapy can be preferred to improve Cobb angle and reduce trunk rotation angle in adolescent idiopathic scoliosis patients.In addition,Schroth therapy may be the best treatment to improve the quality of life of adolescent idiopathic scoliosis patients.Limited by the quantity and quality of the included studies,the above conclusions should be interpreted with caution and need more high-quality studies to further validation.

METTL3 and METTL14 are two components that form the core heterodimer of the main RNA m6A methyltransferase complex (MTC) that installs m6A. Surprisingly, depletion of METTL3 or METTL14 displayed distinct effects on stemness maintenance of mouse embryonic stem cell (mESC). While comparable global hypo-methylation in RNA m6A was observed in Mettl3 or Mettl14 knockout mESCs, respectively. Mettl14 knockout led to a globally decreased nascent RNA synthesis, whereas Mettl3 depletion resulted in transcription upregulation, suggesting that METTL14 might possess an m6A-independent role in gene regulation. We found that METTL14 colocalizes with the repressive H3K27me3 modification. Mechanistically, METTL14, but not METTL3, binds H3K27me3 and recruits KDM6B to induce H3K27me3 demethylation independent of METTL3. Depletion of METTL14 thus led to a global increase in H3K27me3 level along with a global gene suppression. The effects of METTL14 on regulation of H3K27me3 is essential for the transition from self-renewal to differentiation of mESCs. This work reveals a regulatory mechanism on heterochromatin by METTL14 in a manner distinct from METTL3 and independently of m6A, and critically impacts transcriptional regulation, stemness maintenance, and differentiation of mESCs.
Animals ; Mice ; Methylation ; Chromatin ; Histones/metabolism* ; RNA, Messenger/genetics* ; Methyltransferases/metabolism* ; RNA/metabolism*

Objective To investigate the efficacy of different courses of saccharomyces boulardii powder combined with triple therapy in eradicating helicobacter pylori(Hp)in children.Methods A total of 135 children with Hp-related gastritis who received initial treatment in the Department of Pediatrics,Affiliated Hospital of Xuzhou Medical University from October 2021 to June 2022 were selected and divided into three groups according to random number table method:group A,group B and group C,with 45 cases in each group.Group A:triple therapy(omeprazole + clarithromycin + amoxicillin)for 14 days;group B and group C:on the basis of triple therapy,saccharomyces boulardii powder was added from the first day of treatment for 2 weeks and 4 weeks,respectively.The adverse reactions during treatment were recorded,the levels of serum pepsinogen Ⅰ(PGⅠ)and pepsinogen Ⅱ(PGⅡ),clinical efficacy and Hp eradica-tion rate were observed 4 weeks after the end of treatment.Results The levels of serum PGⅠ and PGⅡ in the three groups after treat-ment were significantly lower than those before treatment(P<0.05),the levels of serum PGⅠ and PGⅡ in group B and group C after treatment were lower than those in group A(P<0.05),and the levels of serum PGⅠ and PGⅡ in group B were lower than those in group C after treatment(P<0.05).The clinical effective rates of group B(93.0%)and group C(90.4%)were higher than those of group A(62.5%)(P<0.05).The clinical effective rate of group B was higher than that of group C(P>0.05).The Hp eradication rate of group B and group C was significantly higher than that of group A(P<0.05),and the Hp eradication rate of group B was higher than that of group C(P>0.05).The incidence of diarrhea and loss of appetite in group B and group C were lower than those in group A(P<0.05);the incidence of diarrhea and loss of appetite in group B was lower than that in group C(P<0.05).There was no signifi-cant difference in the incidence of abdominal pain,nausea and vomiting among the three groups(P>0.05).Conclusion Saccharomy-ces boulardii decoction combined with triple therapy for 2 or 4 weeks can effectively regulate PG level,improve the eradication rate of Hp,and reduce the incidence of adverse reactions.It is suggested that 2 weeks is the best course of treatment.