Protein phosphatase 2A(PP2A)is one of the major serine-threonine protein phosphatases in mammalian cells which plays an important role in regulating biological activities such as cellular mitosis and protein dephosphorylation.PP2A acts as a tumor suppressor and has been demonstrated to be genetically altered or functionally inactivated in a variety of solid cancers and leukemias,and its activity is inhibited,leading to subsequent proliferation of tumor cells.Clinical studies have shown that endogenous inhibitors such as SET,cancerous inhibitor of PP2A(CIP2A)and protein phosphatase methylesterase-1(PME-1)may reduce PP2A activity,which could be important indicators of tumor progression or recurrence.On the other hand,PP2A-activating drugs(e.g.FTY720)can restore the tumor-suppressing activity of PP2A by altering the structure of the inhibitor SET,thus effectively inhibiting tumor development.Therefore,PP2A and its inhibitors may serve as potential therapeutic targets in clinic.This article provides a comprehensive review on the mechanism of action of PP2A and its inhibitors in the pathogenesis of malignant tumor as well as their applications in oncotherapy,aiming to provide new directions for the treatment of malignant tumors.

Protein phosphatase 1(PP1)is a widely expressed and highly conserved serine/threonine phosphatase in organisms.It regulates cellular signaling pathways by catalyzing the dephosphorylation of various proteins,thereby influencing biological processes such as cell proliferation,apoptosis,migration,and transcription.In vivo,PP1 does not exist as a free catalytic subunit but instead forms distinct PP1 holoenzymes by binding with at least one PP1-interacting protein(PIP).The interaction between PP1's catalytic subunit and its specific regulatory proteins is central to PP1's function.Under normal conditions,PP1 stably performs its dephosphorylation role in vivo;however,in tumors,PP1 function is aberrantly regulated,leading to either increased or decreased PP1 activity.PP1 exerts a dual influence on tumorigenesis and progression,acting as a suppressor in some cancers while promoting oncogenesis in others.Based on domestic and international research findings on PP1,this review summarizes the structure and biological functions of PP1,as well as the impact of its various subunits on the development and progression of different cancers,including breast cancer,lung cancer,ovarian cancer,pancreatic adenocarcinoma(PAAD),liver cancer,endometrial cancer,esophageal cancer(EC),colorectal cancer,and glioblastoma(GBM).This review aims to provide the insights for developing highly efficient and environmentally friendly anticancer drugs and therapeutic approaches targeting PP1 holoenzymes.

Objective:To observe the effect of combining robot-assisted gait training (RAGT) with task-oriented training (TOT) on the walking ability of children with dyskinetic cerebral palsy (DCP).Methods:Sixty DCP children were randomly divided into a conventional intervention group, an RAGT group, and a combined intervention group, each of 20. All of the children received conventional rehabilitation therapy, while the RAGT and combined intervention groups were additionally provided with RAGT, and RAGT combined with TOT, respectively. Before the experiment and after 12 and 24 weeks of treatment, the subjects′ walking ability was evaluated using the 10-metre walk test (10MWT), and the D energy zone (standing position) and the E energy zone (walking, running and jumping) of the Gross Motor Function Measurement-88 (GMFM-88) instrument.Results:After 12 and 24 weeks of treatment, the average 10MWT speed and D and E energy zone scores of all three groups had improved significantly. After 24 weeks the combined group′s averages on all three measures were significantly better than those of the other two groups.Conclusion:RAGT combined with TOT and conventional rehabilitation training significantly improves the walking ability of DCP children.

Objective To explore the therapeutic effects of different doses of radioactive iodine-131 on patients with hyperthyroidism.Methods A total of 574 patients with hyperthyroidism treated in the First Affiliated Hospital of Xinxiang Medical University from April 2020 to April 2023 were sampled for this study and were divided evenly into the observation group and the control group by a random number table,with 287 patients in each group.The control group was treated with high-dose radioactive iodine-131(＞10-15 mCi),while the observation group was provided with low-dose radioactive iodine-131(5-10 mCi).The therapeutic effects were estimated six months after treatment.Data of the two groups of patients before treatment and 3 and 6 months after treatment were compared,including the levels of thyroid hormone(FT4),free triiodothyronine(FT3),and thyroid-stimulating hormone(TSH),which were measured through the fluorescence immunochromatography of serum(obtained by centrifugation of 3 mL fasting venous blood),and the tumor necrosis factor-α(TNF-α),transforming growth factor-β1(TGF-β1),interleukin-6(IL-6),and IL-1,which were measured through the enzyme-linked immunosorbent assay of serum.The salivary gland uptake index and salivary gland secretion index of the patients before treatment and 3 and 6 months after treatment were measured through radionuclide imaging.The incidence of adverse reactions during treatment was documen-ted.The incidence of hypothyroidism in both groups was evaluated 6 months after treatment.Results The total effective rate of the observation group and the control group was 83.27％(234/281)and 92.88％(261/281),respectively,and that of the observation group was significantly higher(x2=12.353,P＜0.05).The FT4,FT3,and TSH levels of the two groups before treatment showed no statistical discrepancy(P＞0.05).According to data collected 3 and 6 months after treatment,FT4 and FT3 levels of both groups significantly decreased,while TSH increased(P＜0.05)compared to corresponding pre-treatment levels;FT4 and FT3 levels of both groups observed 6 months after treatment were significantly lower than those observed 3 months before,in contrast to the growing TSH trend(P＜0.05).At 3 and 6 months after treatment,FT4 and FT3 levels of the observation group were significantly lower than those of the control group,while TSH levels were significantly higher(P＜0.05).The salivary gland uptake index and salivary gland secretion index between the two groups before treatment showed no statistical discrepancy(P＞0.05).At 3 and 6 months after treatment,such indexes of both groups obviously decreased(P＜0.05).However,those observed 6 months after treatment were higher than three months before(P＜0.05).At 3 months after treatment,the salivary gland uptake index and salivary gland secretion index of the observation group were notably higher than the control group(P＜0.05);at 6 months after treatment,no statistical discrepancy was observed between the two groups in terms of the two indexes(P＞0.05).Before treatment,there was no statistical difference in TNF-α,TGF-β1,IL-6,and IL-1 levels between the two groups(P＞0.05).At 3 and 6 months after treatment,the TNF-α,TGF-β1,IL-6,and IL-1 levels of both groups decreased significantly from pre-treatment levels(P＜0.05),and the data observed 6 months after treatment were still lower than those observed 3 months after treatment(P＜0.05).At 3 months after treatment,the TNF-α,TGF-β1,IL-6,and IL-1 levels of the observation group were significantly lower than those of the control group(P＜0.05);at 6 months after treatment,no statistical difference was observed between the two groups(P＞0.05).The incidence of adverse reactions during treatment in the control group and the observation group was 16.38％(47/287)and 8.01％(23/287),respectively,and that of the observation group was significantly lower than the other group(x2=8.457,P＜0.05).At 6 months after treatment,the incidence of hypothyroidism in the control group and the observation group was 12.46％(35/281)and 3.56％(10/281),respectively,and that of the observation group was significantly lower than that in the control group(x2=15.098,P＜0.05).Conclusion Low doses of radioactive iodine-131 work better in the treatment of hyperthyroidism and can effectively alleviate inflammation and salivary gland dysfunction,with less risk of inducing hypothyroidism and adverse reactions.

Objective:To discuss the regulatory effect of serum and glucocorticoid-induced protein kinase 1(SGK1)in the early development of fertilized eggs at G1 phase of the mice,and to clarify the related mechanism.Methods:Some female mice aged 4-6 weeks and weighed about 20 g,and several male mice aged over 8 weeks and weighed about 30 g were selected.The female mice were intraperitoneally injected with 10 IU of pregnant mare serum gonadotropin(PMSG),followed by 10 IU of human chorionic gonadotropin(HCG)after 48 h.After HCG injection,the female mice were caged overnight with the male mice at a ratio of 1∶1.The fertilized eggs at G1,S,G2,and M phases were collected at 12-21 h,21-26 h,26-28 h,and 28-30 h after injected with HCG,and their cellular morphology at different cell cycles were observed under light microscope.The mouse fertilized eggs at G1 phase after superovulation were collected,the mRNA was synthesized in vitro,and divided into no injection group,Tris-EDTA buffer injection group(TE injection group),and SGK1-mRNA injection group.The SGK1 antibodies were mixed with KSOM culture medium with the concentrations of 1∶25,1∶50,1∶100,1∶200,and 0 to culture the mouse fertilized eggs at G1 phase.Western blotting method was used to detect the expression levels of SGK1 protein in fertilized eggs of the mice in various groups and the dephosphorylation for phosphorylated SGK1-Threonine 256 site tyrosine15 site of cell diusion cyclin 2(Cdc2)(Cdc2-pTyr15)in the fertilized eggs of the mice in various groups and different concentrations of SGK1 antibody groups and the developmental states of the fertilized eggs in the fertilized eggs of the mice in various groups and different concentrations of SGK1 antibody groups were observed under phase contrast microscope;the expression levels of phosphorylated SGK1-Thr256(SGK1-pThr256)and Cdc2-pTyr15 proteins in fertilized eggs at different post-HCG injection times were detected by Western blotting method.Results:Compared with no injection and TE injection groups,the expression level of SGK1 protein in the cells in SGK1-mRNA injection group was significantly increased(P<0.01).27-28 h after injected with HCG,the phosphorylation signaling of Cdc2-pTyr15 in fertilized eggs of the mice in SGK1-mRNA injection group was gradually disappeared,and there was no phosphorylation signaling 29 h after injected with HCG.At 28-29 h after injected with HCG,the phosphorylation signaling of Cdc2-pTyr15 in fertilized eggs of the mice in no injection and TE injection groups gradually disappeared,completely disappeared at 30 h after injected with HCG.With the increasing of the concentration of SGK1 antibody,the disappearing time of the Cdc2-pTyr15 phosphorylation signaling was increased.At 27 h after injected with HCG,the fertilized eggs of the mice in SGK1-mRNA injection group was initiated cleavage;at 31 h after injected with HCG,nearly all the fertilized eggs turned into G2 phase;at 33 h after injected with HCG,all the fertilized eggs in 0 and 1∶200 SGK1 antibody groups underwent cleavage.However,with the increasing of SGK1 antibody concentration,the cleavage of the fertilized eggs in 1∶25,1∶50,and 1∶100 SGK1 antibody groups was gradually decreased,particularly at 1∶25 SGK1 antibody group.Compared with no injection and TE injection groups,the death rate of the fertilized eggs of the mice in SGK1-mRNA injection group was significantly decreased at 31 h after injected with HCG(P<0.05),and the cleavage rate was increased(P<0.05).With the increasing of the SGK1 antibody concentration,the death rates of the fertilized eggs in different concentrations of SGK1 antibody group were increased(P<0.05),with the extending of cleavage time was increased,and the cleavage rate of the fertilized eggs was decreased in a dose-dependent manner,and the cleavage rate of fertilized eggs in 1∶25 SGK1 antibody group was the lowest.The expression level of SGK1-pThr256 protein in fertilized eggs of the mice was gradually increased from 27 h after injected with HCG(P<0.05 or P<0.01)in a time-dependent manner;at 28 to 29 h after injected with HCG,the expression levels of Cdc2-Tyr15 protein were gradually decreased(P<0.05)in a time-dependent manner,and had completely disappeared at 30 h after injected with HCG.Conclusion:Both the over-expression and inhibition of SGK1 can affect the time for the fertilized eggs at G1 phase to entry into M phase,suggesting that SGK1 protein may be one of the regulatory factors in the early development of fertilized eggs at G1 phase of the mice,and it may regulate the development of the fertilized eggs at G1 phase through regulation of Cdc2.

Objective:To discuss the role of serum and glucocorticoid-induced protein kinase 3(SGK3)in the resumption of the first meiotic division in the oocytes of the mice,and to preliminarily clarify the regulatory mechanism of SGK3 in the early development of mammalian oocytes.Methods:The germinal vesicle(GV)stage mouse oocytes were obtained by superovulation techniques.The SGK3 mRNA,obtained from in vitro transcription of expression plasmids,was injected into the GV stage oocytes by microinjection techniques.The oocytes were divided into control group,Tris-EDTA buffer(TE)group,and SGK3 mRNA group.Western blotting method was used to detect the expression levels of SGK3 protein in the oocytes in various groups;the germinal vesicle breakdown(GVBD)rates of the oocytes in various groups were observed and calculated at 1,2,3,and 4 h after microinjection of SGK3 mRNA;the morphological appearance of the oocytes in various groups was observed by SGK3 antibody dilution inhibition experiment;Western blotting method was used to detect the expression levels of phosphorylated SGK3(pSer48)(SGK3-pSer48)and phosphorylated cell division cycle protein 2(CDC2)(pTyr15)(CDC2-pTyr15)proteins in the oocytes cultured in vitro at different time points.Results:Compared with control group and TE group,the expression level of SGK3 protein in the oocytes in SGK3 mRNA group was increased(P＜0.01),and the GVBD rates at 1 and 2 h after microinjection were increased(P＜0.01).The SGK3 antibody dilution inhibition experiment results showed that as the increasing of concentration of SGK3 antibody,the GVBD rates of the oocytes in various groups were decreased in a concentration-dependent manner.After overexpressing SGK3,compared with control group,the time when CDC2-pTyr15 protein expression could not be detected in the oocytes in SGK3 mRNA group was advanced by at least 1 h.After treated with different concentrations of SGK3 antibody,compared with control group,as the increasing of concentration of SGK3 antibody and the extending of treatment time,the expression level of CDC2-pTyr15 protein in the oocytes was gradually decreased(P＜0.01),and the expression level of SGK3-pSer486 protein was gradually increased(P＜0.01).Conclusion:Over-expression of SGK3 can increase the GVBD rate of oocytes of the mice and accelerate the dephosphorylation of CDC2-pTyr15,while the dephosphorylation of CDC2-pTyr15 is later than the phosphorylation of SGK3-Ser486.SGK3 likely serves as an upstream regulator of CDC2 and participates in controlling the resumption of the first meiotic division in the oocytes of the mice.

Objective:To deeply explore the real work of primary, secondary and tertiary prevention of stroke in general hospitals, rehabilitation and pension institutions and community health service centers (stations), and to provide reference for improving the level of comprehensive prevention of stroke in the medical system.Methods:From July to November 2022, face-to-face semi-structured interviews with 18 medical staff in general hospitals, 10 medical staff in rehabilitation and pension institutions, and 8 medical staff in community health service centers (stations) were conducted by phenomenological research methods. Colaizzi 7-step analysis method was used to analyze the interview data, and Nvivo12 software was used to code the interview data.Results:Four themes were extracted: hospitals, institutions and communities all played an important role in the comprehensive prevention of stroke and actively cooperated with each other; the public was still lack of comprehensive prevention awareness and correct cognition of stroke; lack of professional medical resources hindered the development of comprehensive stroke prevention; incomplete collaborative mechanism of comprehensive prevention of stroke in hospitals, institutions and communities.Conclusions:In the current comprehensive prevention of stroke, there are still problems such as weak public awareness of prevention, insufficient professional medical resources, and imperfect coordination mechanism. In view of the advantages of medical institutions at all levels, it is necessary to clarify the responsibilities of the system at all levels and explore efficient and sustainable coordination mechanism, so as to improve the comprehensive prevention level of stroke in the medical system.

ObjectiveTo explore the possible mechanism of Tongdu Xingshen needling method （通督醒神针刺法） on post-stroke cognitive impairment. MethodsSD rats were randomly divided into a normal group （n=12）， a sham surgery group （n=12）， a model group （n=12）， and a electroacupuncture group （n=13）. The rats in the model group and electroacupuncture group were subjected to the wire bolus method to establish the rats model with learning memory impairment after cerebral ischaemia-reperfusion. After successful modelling， the rats in the electroacupuncture group were given electroacupuncture interventions at “Shenting （GV 24）” and “Baihui （GV 20）” once a day for 30 minutes for 14 days. The other three groups did not receive other interventions but grasp. A 5-day localisation navigation experiment was conducted on the 9th day of intervention， and a spatial exploration experiment was conducted on the 14th day of intervention to evaluate the learning and memory abilities of the rats. After the spatial exploration experiment， hippocampal tissues were taken from each group of rats， and the changes in the volume of cerebral infarction were observed by TTC staining； the changes in the morphology of pyramidal neurons and the density of dendritic spines in the CA1 area of the hippocampus were observed by Golgi staining； protein immunoblotting was used to detect the relative protein expression of the subunits of the α-amino-3-carboxy-5-methylisoxazole-4-propionic acid （AMPA） receptor including glutamate receptor 1 （GluR1）， glutamate receptor 2 （GluR2）， glutamate receptor 3 （GluR3） and auxiliary proteins TARPγ2， TARPγ8 in hippocampal tissues of rats in each group； the real-time fluorescence quantitative PCR was used to detect GluR1， GluR2， GluR3 mRNA levels in the hippocampal tissues of rats. ResultsIn the localisation navigation experiment， compared with the normal group and sham surgery group， the escape latency and total distance of rats in the model group were significantly extended （P＜0.05） at day 1， 2， 3， 4， and 5； and the escape latency and total distance of rats in the electroacupuncture group tended to be significantly shorter than those in the model group （P＜0.05）. In the spatial exploration experiment， compared with the normal group and the sham surgery group， the number of rats crossing the platform in the model group was significantly reduced （P＜0.05）， and the number of crossings of the platform in the electroacupuncture group increased significantly （P＜0.05）. The results of TTC staining showed that the volume of cerebral infarction increased clearly in the model group compared with the sham surgery group （P＜0.05）， and apparently decreased in the electroacupuncture group compared with the model group （P＜0.05）. Golgi staining showed that the number of dendritic branches of pyramidal neurons and dendritic spines in hippocampal CA1 region significantly decreased in the model group compared with the normal group and the sham surgery group （P＜0.05）. The number of dendritic branches of pyramidal neurons and the density of dendritic spines in hippocampal CA1 region significantly increased in the electroacupuncture group compared with the model group （P＜0.05）. The protein relative expression levels of GluR1， GluR2， GluR3， TARPγ2 and TARPγ8， and the mRNA levels of GluR1， GluR2 and GluR3 in hippocampus decreased in the model group compared with the normal group and the sham surgery group （P＜0.05）. The protein relative expression levels of GluR1， GluR2， GluR3， TARPγ2 and TARPγ8， and the mRNA levels of GluR1， GluR2 and GluR3 in hippocampus increased in the electroacupuncture group compared with model group （P＜0.05）. ConclusionThe Tongdu Xingshen needling method can improve learning memory impairment after cerebral ischaemia-reperfusion， which may be related to up-regulation of the expression of AMPA receptor and their auxiliary protein TARP， and promoting the synaptic plasticity of hippocampal tissues.

【Objective】 To study the changes of platelet components(PC), apheresis platelets (AP) and pooled platelet concentrates (PPC) production of 19 provincial blood centers before and during the COVID-19 epidemic. 【Methods】 The data related to the collection of AP and the preparation of PPC from 2016 to 2021 of 19 provincial blood centers was collected. The production of PC, AP and PPC during the four years before the epidemic (i.e. 2016-2019) and during the COVID-19 epidemic (i.e. 2020 and 2021) were calculated respectively, and the change of production was analyzed. 【Results】 The total production of PC in 19 blood centers steadily increased from 2016 to 2019, with a decrease of 4.16% in 2020 and an increase of 15.60% in 2021, exceeding the output before the COVID-19 epidemic. In 2020, the production of PC of 42.11% (8/19) blood centers decreased compared with 2019, while 94.74% (18/19) in 2021 increased compared with 2020. The changes of AP output was basically consistent with the trend of PC. The total production of PPC in 2017 and 2018 both doubled compared to the previous year, while decreased by 67.98% in 2019, increased by 30.38% in 2020 and decreased by 27.08% in 2021. 【Conclusion】 The total production of PC kept increasing steadily between 2016 and 2019, but decreased in 2020 under the COVID-19 epidemic, with some blood centers being significantly affected. In 2021, with the strong support from government and various measures by blood centers, the total production of PC increased.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.