Objective To investigate the role of miR-147a targeting inhibin subunit beta A(INHBA)in transforming growth factor-β1(TGF-β1)/Smads signaling pathway in the invasion and metastasis of cervical cancer HeLa cells.Methods The miR-147a mimics,miR-147a inhibitors and their negative controls(mimicsNC and inhibitor NC)were transfected into HeLa cells and divid-ed into five groups:control group(blank control),mimics NC group,miR-147a mimics group,inhibitor NC group,and miR-147a in-hibitor group.The proliferation activity of HeLa cells after miR-147a intervention was detected by the MTT method,the invasion and me-tastasis abilities of HeLa cells after the intervention of miR-147a were detected by Transwell and cell scratch assay,the mRNA expres-sion changes of miR-147a and INHBA in different groups were detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR),the relationship between miR-147a and the target gene INHBA was detected by dual-luciferase reporter gene assay,the protein expressions of TGF-β1,TGFBR1,Smad3,Smad2 and INHBA in different groups were detected by Western blot,and the ex-pression changes of TGF-β1 were detected by enzyme-linked immunosorbent assay(ELISA).Results Compared with blank control and negative control,miR-147a mimics inhibited cell proliferation,decreased cell invasion and migration ability,and decreased cell healing ability.miR-147a inhibitor promoted cell proliferation,increased invasion and migration ability,and improved cell healing abili-ty.In the miR-147a mimics group,miR-147a was significantly increased,and the target gene INHBA was significantly decreased(P＜0.05).In the miR-147a inhibitor group,miR-147a was significantly decreased,and the target gene INHBA was significantly in-creased(P＜0.05).The fluorescence intensity ratio of miR-147a mimics+WT group was significantly lower than that of mimics NC+WT group(P＜0.05).The expression levels of TGFBR1,TGF-β1,Smad3,Smad2 and INHBA in miR-147a mimics group were sig-nificantly decreased(P＜0.05).The expression levels of TGFBR1,TGF-β1,Smad3,Smad2,and INHBA in miR-147a inhibitor group were significantly increased(P＜0.05).Conclusion miR-147a targets the TGF-β1/Smads signaling pathway mediated by IN-HBA,which plays an important role in inhibiting the proliferation,invasion and migration of cervical cancer HeLa cells,and provides a potential molecular target and theoretical basis for the treatment of cervical cancer.

Objective To compare the effect of different intensity of neuromuscular training(NMT)on muscle strength and knee joint function of patients after anterior cruciate ligament reconstruction(ACLR).Methods From January,2023 to January,2024,60 ACLR patients in Changhai Hospital were selected,and they received the same intensity of NMT from one to eight weeks after surgery.Eight weeks after surgery,they were randomly divided into low intensity group(n=30)and high intensity group(n=30),and then they received different inten-sities of NMT from nine to 16 weeks after surgery,each training session lasted one hour,with three sessions per week,totaly 48 sessions.The Lysholm score,knee flexor and extensor muscle strength and muscle endurance-were compared at eight weeks and 16 weeks after surgery.Results After group training,the Lysholm score significantly increased in both groups(|t|>13.739,P<0.001),and was higher in the high intensity group than in the low intensity group(t=-2.574,P<0.05);in the high intensity group,the relative peak torque and endurance of the extensor and flexor muscles improved at angular velocities of 60°/s,120°/s and 180 °/s(|t|>2.320,P<0.05);in the low intensity group,the flexor peak torque improved at all the three angular velocities(t>2.177,P<0.05),the extensor peak torque improved at angular velocities of 60°/s and 180°/s(|t|>1.715,P<0.05),and the extensor endurance improved at angular velocity of 60°/s(t=-2.293,P<0.05).However,there was no significant difference in the relative peak torque and endurance of the extensor and flexor muscles at all the three angular velocities(P>0.05).Conclusion Both high and low intensity NMT could improve the muscle strength,muscle endurance and knee joint func-tion.Maybe,high intensity is superior to low intensity.Further verification is still needed.

Objective To investigate the role of miR-147a targeting inhibin subunit beta A(INHBA)in transforming growth factor-β1(TGF-β1)/Smads signaling pathway in the invasion and metastasis of cervical cancer HeLa cells.Methods The miR-147a mimics,miR-147a inhibitors and their negative controls(mimicsNC and inhibitor NC)were transfected into HeLa cells and divid-ed into five groups:control group(blank control),mimics NC group,miR-147a mimics group,inhibitor NC group,and miR-147a in-hibitor group.The proliferation activity of HeLa cells after miR-147a intervention was detected by the MTT method,the invasion and me-tastasis abilities of HeLa cells after the intervention of miR-147a were detected by Transwell and cell scratch assay,the mRNA expres-sion changes of miR-147a and INHBA in different groups were detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR),the relationship between miR-147a and the target gene INHBA was detected by dual-luciferase reporter gene assay,the protein expressions of TGF-β1,TGFBR1,Smad3,Smad2 and INHBA in different groups were detected by Western blot,and the ex-pression changes of TGF-β1 were detected by enzyme-linked immunosorbent assay(ELISA).Results Compared with blank control and negative control,miR-147a mimics inhibited cell proliferation,decreased cell invasion and migration ability,and decreased cell healing ability.miR-147a inhibitor promoted cell proliferation,increased invasion and migration ability,and improved cell healing abili-ty.In the miR-147a mimics group,miR-147a was significantly increased,and the target gene INHBA was significantly decreased(P＜0.05).In the miR-147a inhibitor group,miR-147a was significantly decreased,and the target gene INHBA was significantly in-creased(P＜0.05).The fluorescence intensity ratio of miR-147a mimics+WT group was significantly lower than that of mimics NC+WT group(P＜0.05).The expression levels of TGFBR1,TGF-β1,Smad3,Smad2 and INHBA in miR-147a mimics group were sig-nificantly decreased(P＜0.05).The expression levels of TGFBR1,TGF-β1,Smad3,Smad2,and INHBA in miR-147a inhibitor group were significantly increased(P＜0.05).Conclusion miR-147a targets the TGF-β1/Smads signaling pathway mediated by IN-HBA,which plays an important role in inhibiting the proliferation,invasion and migration of cervical cancer HeLa cells,and provides a potential molecular target and theoretical basis for the treatment of cervical cancer.

Objective To compare the effect of different intensity of neuromuscular training(NMT)on muscle strength and knee joint function of patients after anterior cruciate ligament reconstruction(ACLR).Methods From January,2023 to January,2024,60 ACLR patients in Changhai Hospital were selected,and they received the same intensity of NMT from one to eight weeks after surgery.Eight weeks after surgery,they were randomly divided into low intensity group(n=30)and high intensity group(n=30),and then they received different inten-sities of NMT from nine to 16 weeks after surgery,each training session lasted one hour,with three sessions per week,totaly 48 sessions.The Lysholm score,knee flexor and extensor muscle strength and muscle endurance-were compared at eight weeks and 16 weeks after surgery.Results After group training,the Lysholm score significantly increased in both groups(|t|>13.739,P<0.001),and was higher in the high intensity group than in the low intensity group(t=-2.574,P<0.05);in the high intensity group,the relative peak torque and endurance of the extensor and flexor muscles improved at angular velocities of 60°/s,120°/s and 180 °/s(|t|>2.320,P<0.05);in the low intensity group,the flexor peak torque improved at all the three angular velocities(t>2.177,P<0.05),the extensor peak torque improved at angular velocities of 60°/s and 180°/s(|t|>1.715,P<0.05),and the extensor endurance improved at angular velocity of 60°/s(t=-2.293,P<0.05).However,there was no significant difference in the relative peak torque and endurance of the extensor and flexor muscles at all the three angular velocities(P>0.05).Conclusion Both high and low intensity NMT could improve the muscle strength,muscle endurance and knee joint func-tion.Maybe,high intensity is superior to low intensity.Further verification is still needed.

BACKGROUND:Intervertebral disk degeneration is a pathological change caused by a series of complex molecular mechanisms that result in the aging and damage of intervertebral discs,ultimately leading to severe clinical symptoms.Traditional Chinese medicine has unique advantages in the treatment of intervertebral disk degeneration due to its low cost,non-addictive nature,multi-target effects,minimally toxic and side effects,and high patient acceptance. OBJECTIVE:To review the latest research results of traditional Chinese medicine monomer intervention-related signaling pathways in the treatment of intervertebral disk degeneration,describe and analyze the action mechanism of traditional Chinese medicine monomer on intervertebral disk degeneration,and provide a new approach and theoretical basis for future basic research and clinical treatment. METHODS:The first author searched for relevant literature from January 2018 to February 2023 in CNKI,PubMed,VIP,and WanFang using the search terms"intervertebral disc,signal pathway".The articles that did not meet the criteria were excluded after preliminary screening of the titles and abstracts.Finally,72 articles were selected for review and analysis. RESULTS AND CONCLUSION:Traditional Chinese medicine monomers can regulate multiple classical signaling pathways such as Wnt/β-catenin,PI3K/Akt,mTOR,NF-κB,and MAPK.They achieve this by regulating oxidative stress,adjusting the expression of pro/anti-apoptotic proteins in cells,stimulating cellular autophagy function,reducing stimulation of cell inflammatory factors,increasing the expression of extracellular matrix markers,reducing the production of matrix-degrading enzymes,maintaining the synthesis and stability of extracellular matrix,inducing differentiation of mesenchymal stem cells in the nucleus pulposus into nucleus pulposus cells,promoting endogenous repair and reconstruction,controlling apoptosis and aging of nucleus pulposus cells,and increasing the activity of nucleus pulposus cells.These actions improve the microenvironment within the intervertebral disc,maintain the normal physiological function of the intervertebral disc,and delay intervertebral disc degeneration.

Objective To investigate the clinical significance of nuclear factor ( NF)-κB activation in peripheral blood mononuclear cells (PBMCs) and the serum levels of correlated inflammatory cytokines in children with infant muggy syndrome(IMS).Methods Blood samples from 100 patients with IMS and those from 32 healthy infants( control group)were detected by ELISA for amount of NF-κB activation in PBMCs and for serum levels of interleukin ( IL ) -17,IL-6,tumor necrosis factor ( TNF ) -α and IL- 10 respectively from Jan 2008 to Jan 2011.At the same time,blood samples from 46 out of the above 100 patients with IMS and those from the 32 controls for positive rate of activation of NF-κB in PBMCs were detected by flow cytometry as well.The relationship between all the data and multiple organ dysfunction syndrome( MODS ) were analyzed respectively.Results As compared with that of control group,the percentage of activated NF-κB in PBMCs in 100 patients with IMS detected by ELISA [ ( 11.042 ± 6.792 ) ％ vs ( 4.528 ± 1.378 ) ％ ] and the positive rate of NF-κB activation in 46 patients with IMS detected by flow cytometry [ ( 28.780 ± 13.820 ) ％ vs (7.078 ±5.395)％ ] were both significantly higher ( P ＜0.01 ).The serum levels of IL-17,IL-6 and IL-10were also significantly higher in patients with IMS than those in control group( P ＜0.01 ).The serum level of TNF-α was higher in patients with IMS than that in control group but without significance( P ＞ 0.05 ).The percentage of activated NF-κB [ ( 14.591 ± 7.626) ％ vs ( 8.576 ± 4.851 ) ％ ],the positive rate of NF-κB activation [ ( 36.087 ± 12.056) ％ vs ( 23.590 ± 11.263 ) ％ ],and the serum levels of IL- 17,IL-6,TNF-α and IL-10 were all significantly higher in IMS patients with MODS than those in IMS patients without MODS ( P ＜ 0.01 ).Conclusion The inflammatory factors of NF-κB activation in PBMCs and the high serum levels of IL-17 and IL-6 are potent to cause inflammatory damage in IMS patients,and the serum level of IL-10 is not able to compensate the damage.The activation of NF-κB and high serum levels of IL-17,IL-6 and TNF-α are correlated with MODS.

Objective As estrogen increases visceral hypersensitivity induced by water avoidance stress in female rats,further experiment was designed to determine whether the influence of estrogen involves NR2B.Methods Healthy adult female Wistar rats were bilaterally ovariectomized,and then housed individually.Implantation of cannula into lateral cerebroventricle and electrodes into the abdominal muscle had been done.After 5 days recovery,rats with abnormal behavior and ehctromyography were excluded,finally a total of 48 rats were eligible,and were equipped for abdominal muscle electromyography and submitted to water avoidance stress(WAS).Visceromotor response(VMR)to 20,40,60 and 80 mmHg colorectal distension(CRD)was recorded in rats intracerebroventricular-infused with either 17β-estradiol,normal saline,AP5(NMDA receptor-antagonist)or Ro25-6981(NR2B antagonist).NR2B mRNA in anterior cingulate cortex or dorsal root ganglia were compared by real-time PCR between the rats treated with 17β-estradioI and that with normal saline.Results Bilaterally ovarieetomized rats treated with 17β-estradiol,exhibited more visceral hypersensitivity after WAS than that with normal saline on 40,60 and 80 mmHg CRD(P=0.039,P=0.033,P=O.001).The VMR on 40 and 60 mmHg CRD in 17β-estradiol treated group was not significantly different from that in 17β-estradiol plus Ro25-6981 treated group.Whilst,significant differences of VMR were noted between 17β-estradiol treated group and 17β-estradiol plus Ro25-6981 treated group on 80 mmHg CRD,17β-estradiol treated group and 17β-estradiol plus AP5 treated group on 60,80 nmmHg CRD,respectively.17β-estradiol increased NR2BmRNA in anterior cingulate cortex(0.57±0.41 vs 0.21±0.13,P=0.048),but not in dorsal root ganglia(0.35±0.45 vs 0.38±0.31,P=0.465). Stress-induced visceral hypersensitivity in the hormonally-restored visceral hyper-responsiveness of bilaterally ovariectomized rats was antagonized by AP5 or Ro25-6981.Conclusions Estrogen may be mediated through NR2B activation to enhance visceral sensitivity in female stressed rats,that probably related with the increased expression of NR2B mRNA in anterior cingulate cortex.