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 explore the factors affecting the safety of home environment for device-aided elderly people, so as to provide a basis for improving the safety of the elderly's home environment and promoting aging-adapted reform.Methods:From August 2021 to March 2022, stratified cluster sampling was used to select 326 device-aided elderly people from 8 communities in Urumqi City as the research subject. The survey was conducted using the General Information Questionnaire, Capacity Assessment Standard Table for the Elderly, Home Environment Safety Assessment Scale for the Elderly, and Home Environment Ageing-adapted Reform Cognition and Needs Concise Questionnaire for the Elderly. Multiple linear regression was used to explore the influencing factors of home environment safety for device-aided elderly people.Results:A total of 326 questionnaires were distributed, and 305 valid questionnaires were collected, with an effective recovery rate of 93.56% (305/326) . The influencing factors of home environment safety for device-aided elderly people included housing area, self-evaluation of the home environment, chronic diseases, monthly pension income, and cognition of aging-adapted reform ( P<0.05) . Conclusions:The aging-adapted reform of home environment should focus on elderly people who suffer from chronic diseases, have poor self-evaluation of the environment, have low monthly pension income and cognition of aging-adapted reform. Relevant departments should promote the self-evaluation methods of home environment and knowledge on home aging-adapted reform.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

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.

Objective:To explore the influencing factors of residual thyroid clearance with 131I after surgery in patients with differentiated thyroid cancer (DTC). Methods:A retrospective analysis was conducted on the clinical data of 100 DTC patients admitted to the Hunan Provincial People′s Hospital from January 2018 to February 2021 who underwent 131I treatment for the first time. The success rates of first thyroidectomy using different doses of 131I, different pathological types, and different treatment times were compared, and logistic regression analysis was conducted to investigate the influencing factors of the efficacy of first postoperative 131I thyroidectomy in DTC patients. Results:A total of 54 patients successfully cleared residual thyroid, 46 patients failed to clear residual thyroid, and the success rate of clearing residual thyroid was 54%. The success rates of first clearance of residual thyroid in patients with 131I doses of 80 mCi, 90 mCi, and 100 mCi were 37.50%(12/32), 52.78%(19/36), and 71.88%(23/32), respectively, with statistically significant differences among the groups ( P<0.05); The success rates of first removal of residual thyroid in patients with follicular carcinoma, mixed papillary follicular carcinoma, and papillary carcinoma were 65.71%(23/35), 39.13%(9/23), and 52.38%(22/42), respectively. There was no statistically significant difference between the groups ( P>0.05); The success rates of first removal of residual thyroid in the group1 of patients (treatment time<3 months), the group2 of patients (treatment time 3-12 months), and the group3 of patients (treatment time>12 months) were 68.09%(32/47), 44.44%(16/36), and 35.30%(6/17), respectively. There was no statistically significant difference between the groups ( P>0.05); There was no statistically significant difference in the success rate of clearing residual thyroid in DTC patients of different genders, ages, pathological stages, and thyroid stimulating hormone (TSH) levels (all P>0.05); The difference in the success rate of clearing residual thyroid in DTC patients with different metastatic conditions and stimulating thyroid globulin (sTg) was statistically significant (all P<0.05); sTg, postoperative lymph node metastasis, and postoperative distant metastasis were independent risk factors for the efficacy of residual thyroid clearance in DTC patients for the first time after surgery (all P<0.05). Conclusions:The influencing factors for the efficacy of the first 131I in removing residual thyroid include differences in 131I dosage, presence or absence of metastatic lesions during treatment, Tg levels, etc. Reducing Tg levels is an important factor in improving remission rate, and controlling lymph nodes and distant metastasis is a key factor for the successful efficacy of the first 131I in removing residual thyroid.