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 explore the relationship between glycosylated hemoglobin A 1c/high-density lipoprotein cholesterol ratio (HbA 1c/HDL-C) and urinary albumin-creatinine ratio (UACR) in Chinese adults. Methods:In this cross-sectional study, the clinical data of 43 820 community residents (age>40 years) from the Risk Evaluation of Cancers in Chinese Diabetic Individuals (REACTION study; March-December 2012) across eight centers (Liaoning, Guangdong, Shanghai, Gansu, Guangxi, Henan, Hubei, and Sichuan) in China were collected and analyzed. Participants were divided into three groups based on UACR levels:<10 mg/g, 10-30 mg/g, and >30 mg/g. The HbA 1c/HDL-C ratio was divided into four groups according to quartile division of the subjects: 1st quartile (Q1<3.79), 2nd quartile (3.79≤Q2<4.59), 3rd quartile (4.59≤Q3≤5.66), and 4th quartile (Q4>5.66). Multivariate ordinal logistic regression model was used to analyze the relationship between HbA 1c/HDL-C and UACR. Receiver operating characteristic (ROC) analysis was used to explore the predictive value of HbA 1c/HDL-C to UACR. Results:The 43 820 subjects included 13 452 (30.70%) male and 30 378 (69.30%) female patients, with an average age of (58.00±0.05) years. According to results of one-way analysis of variance analysis, the HbA 1c/HDL-C ratio was significantly associated with the risk of increased UACR ( F=495.73, P<0.001). After adjusting for clinically relevant confounding variables in logistic regression model, compared with participants with the lowest HbA 1c/HDL-C ratio (Q1), women with the highest HbA 1c/HDL-C ratio (Q4) had a 1.483-fold (95% CI 1.376-1.598, P<0.001) and men had a 1.161-fold (95% CI 1.019-1.323, P<0.001) increased risk of UACR. The ROC curve analysis showed that the area under the curve of HbA 1c/HDL-C for predicting increased UACR was 0.623 (95% CI 0.597-0.606), with a sensitivity of 60.18% and a specificity of 54.91%. The HbA 1c/HDL-C ratio showed the highest predictive value of all glycemic and lipidemic parameters. In individuals with well-controlled blood glucose (HbA 1c<6.5%) or lipid levels (HDL-C≥1.0 mmol/L), the HbA 1c/HDL-C ratio was still independently associated with the risk of increased UACR after adjusting for confounding variables [ OR(95% CI) of quartile 4: 1.563 (1.210-2.019, P=0.001) in participants with HbA 1c<6.5% and 1.822 (1.687-1.968, P<0.001) in participants with HDL-C≥1.0 mmol/L]. Conclusion:As a novel compound indicator for evaluating glucose homeostasis and dyslipidemia, the HbA 1c/HDL-C ratio was independently associated with increased UACR in the general population aged>40 years in China, which was superior to both glycemic and lipid parameters alone.

Objective: To analyze the epidemic characteristics and drug resistance of pulmonary tuberculosis among the floating population in Beijing and to provide a scientific basis for formulating strategies for the prevention and control of tuberculosis among the floating population. Methods: Data of tuberculosis patients who were positive for Mycobacterium tuberculosis culture was collected from 16 districts and one municipal institution of tuberculosis control and prevention in Beijing in 2019. The strain samples were tested for drug sensitivity by the proportional method. According to household registration location, patients were divided into the floating population and Beijing registration. SPSS 19.0 software analyzed tuberculosis patients' epidemic characteristics and drug resistance in the floating population. Results: In 2019, there were 1 171 culture-positive tuberculosis patients in Beijing, among the floating population, 593 (50.64%) patients were identified, with a male-to-female sex ratio of 2.2∶1 (409∶184). Compared to patients under household registration as Beijing residents, a higher proportion of young adults aged 20-39 years (65.09%,386/593) were noticed, with 55.65% (330/593) reported from the urban areas and 96.80% (574/593) were reported the first time. The differences were statistically significant (all P<0.05). After completing the drug sensitivity test, 37 cases were with multiple drug-resistant tuberculosis, accounting for 6.24% (37/593). The rates of isoniazid resistance (42.11%,8/19) and multidrug resistance (21.05%,4/19) in floating population patients after retreatment were significantly higher than those in newly treated patients (11.67%, 67/574 and 5.75%, 33/574), and the differences were statistically significant (all P<0.05). Conclusions: Most patients with tuberculosis in the floating population in Beijing in 2019 were young males aged 20-39 years. The reporting areas were urban areas and the newly treated patients mainly. The patients with tuberculosis in the re-treated floating population were more likely to suffer from multidrug and drug resistance, which should be taken as the key population for prevention and control.
Young Adult ; Humans ; Female ; Male ; Beijing/epidemiology* ; Tuberculosis ; Tuberculosis, Pulmonary/epidemiology* ; Tuberculosis, Multidrug-Resistant/epidemiology* ; Drug Resistance

Objective:To understand the genome and genetic evolution characteristics of influenza B virus (FluB) in Suzhou city from July 2021 to January 2022.Methods:Real-time fluorescence reverse transcription polymerase chain reaction (Real-Time RT-PCR) was used for the typing of influenza virus (Flu). The detected FluB strains were sequenced by Miseq high-throughput sequencing platform through whole genome capture and library construction. The FluB hemagglutinin (HA), neuraminidase (NA) and matrix protein (MP) gene phylogenetic trees were constructed by Neighbor-Joining method (NJ) with MEGA X software. The Potential N-glycosylation sites of HA and NA proteins were predicted by NetNGlyc 1.0 server software.Results:FluB was detected in 280 of the 1 500 throat swab samples, and the FluB genome sequence was completed in 53 strains. The nucleic acid identity of 8 gene fragments (PB1, PB2, PA, HA, NP, NA, MP, NS) in the FluB strains was 99.3%-100%, 98.1%-100%, 98.8%-100%, 98.0%-100%, 99.2%-100%, 98.4%-100%, 98.2%-100% and 99.0%-100%, respectively. Except for the 4 samples in July 2021, which belonged to the V1A.3 clade of FluB, the rest of the samples belonged to the V1A.3a.2 clade. Every amino acid sequence of HA protein of Flu B collected after October 2021 showed 9-11 substitutions compared with the reference strain (B/Washington/02/2019), which sharing 9 mutation sites (H122Q, A127T, R133G, P144L, N150K, G184E, N197D, K203R and R279K). No drug-resistant mutations associated with NA inhibitors such as oseltamivir were found. Respectively, 11 and 4 potential glycosylation sites were identified in HA and NA proteins of the FluB strains.Conclusions:From July 2021 to January 2022, V1A.3a2 was the dominant FluB strains in Suzhou city, and the amino acid sequences of HA and NA proteins showed multiple site mutations.

Due to the rapid proliferation and growth of tumor cells, hypoxic microenvironment exists in many solid tumors, and hypoxia inducible factors (HIF) are critical for sensing oxygen tension within tumors and subsequently mediating the activation of hypoxia responses. Hepatocellular carcinoma (HCC) is one of the most hypoxic tumors. This article summarizes the mechanism of action of HIF in promoting the development and progression of HCC by promoting glycolysis, angiogenesis, invasion and metastasis, immune escape, and cancer stem cell formation. At present, the development of targeted drugs for HIF inhibitors has broad prospects in the treatment of HCC, and the detection of HIF also has a potential value in prognostic evaluation HCC.

OBJECTIVE: To investigate the clinical efficacy of high dose methotrexate (HD-MTX), temozolomide (TMZ), and rituximab (R) in the treatment of patients with primary central nervous system lymphoma (PCNSL). METHODS: Clinical data of patients with PCNSL diagnosed and treated in Guangdong Provincial People's Hospital from February 2010 to May 2017 were collected. First, patients were given 6-8 cycles of MTX (3.5 g/m RESULTS: There were 42 patients enrolled in the study, 17 cases in HD-MTX+TMZ group and 25 cases in HD-MTX+TMZ+R group. The median PFS and OS times in HD-MTX+TMZ+R group were 56.7 months and N/A, respectively, while, 7.3 months and 34.7 months in HD-MTX+TMZ group, respectively. In addition, there was no significant difference in median survival between patients who received TMZ maintenance therapy and those who were only actively monitored. During the induction period, all the patients had grade 1-2 nausea and vomiting, while in the consolidation treatment period, no grade 3/4 toxicity was observed. CONCLUSION The combination of HD-MTX+TMZ+R in the treatment of PCNSL patients shows a definite short-term effect, which can increase the survival rate of the patients. The side effects are mild, and the patients can generally tolerate.
Antineoplastic Combined Chemotherapy Protocols ; Central Nervous System ; Central Nervous System Neoplasms/drug therapy* ; Humans ; Lymphoma, Non-Hodgkin/drug therapy* ; Methotrexate/therapeutic use* ; Retrospective Studies ; Rituximab/therapeutic use* ; Temozolomide/therapeutic use* ; Treatment Outcome

Objective:To explore the factors affecting curative effect of motor imagery brain-computer interface (MI-BCI) training on upper limb paralysis for subacute stroke patients. Methods:From January, 2018 to July, 2019, 23 inpatients with post-stroke upper limb paralysis accepting MI-BCI training were reviewed. The gender, age, course of disease, aphasia, location and nature of lesion, history of Botulinum toxin, hemisphere injured and modified Ashworth Scale (MAS) score of affected fingers were recorded, and they were assessed with Fugl-Meyer Assessment-Upper Extremities (FMA-UE) before and four weeks after MI-BCI training. According to improvement of FMA-UE wrist and hand scores (≥ 2), the patients were divided into effective group (n = 11) and inefficacy group (n = 12). Results:The MAS scores before MI-BCI training (t = 2.677, P < 0.05) and history of botulinum toxin (Z = 0.000, P < 0.05) were more in the inefficacy group than in the efficacy group. FMA-UE scores (total and dimensions) after training were correlated to their baseline levels (r > 0.831, P < 0.01), FMA-UE total scores (Eta = 0.453, P < 0.05) and upper arms scores (Eta = 0.506, P < 0.05) were correlated to aphasia, FMA-UE scores of hands were correlated with MAS (r = -0.521, P < 0.05). Conclusion:Poor baseline motor function, spasticity and complication with aphasia were the factors unfavorable to MI-BCI training for subacute stroke patients with upper limb paralysis.

BACKGROUND: Studies have reported that low bone mineral density (BMD) is prevalent in human immunodeficiency virus (HIV)-infected patients; however, the factors that contribute to HIV-related BMD changes are yet to be fully understood. Due to the application of dual X-ray absorptiometry (DXA) among a select group of hospitals only, the prevalence and risk factors of low BMD in HIV-infected populations have not been intensively investigated in China. Thus, the aim of our study was to investigate the prevalence of and risk factors associated with BMD changes among antiretroviral therapy (ART)-naive HIV-positive patients in China. METHODS: The assessment of the prevalence of and risk factors associated with BMD changes was conducted among 156 ART-naive HIV-infected patients. Demographic and clinical data, as well as results of fasting blood tests were obtained from patients. Further, all patients underwent DXA scans to determine BMD, which was then used to classify patients with osteopenia/osteoporosis. The risk factors of reduced BMD were then evaluated using binary logistic regression. RESULTS: Among the 156 ART-naive HIV-infected participants, osteopenia and osteoporosis were diagnosed in 48.7% (76/156) and 4.5% (7/156) of patients, respectively. The lumbar spine was most likely to have reduced BMD (49.4% [77/156]), and the proportion of osteopenia in the left hip (32.7% [51/156]) was higher than in the right hip (24.4% [38/156]). In the lumbar spine, bone loss rate in the L1 section (60.9% [95/156]) was the most significant (L2, 53.2% [83/156]; L3, 45.5% [71/156]; L4, 52.6% [82/156]). Further analysis showed that, compared with the neck (26.9% [42/156] in the left, 18.6% [29/156] in the right) and the interior (15.4% [24/156] in the left, 13.5% [21/156] in the right), the trochanter had the greatest probability of reduced BMD (46.2% [72/156] in the left, 28.8% [45/156] in the right). In the risk factor analysis, low body mass index (BMI: <18.5 kg/m2) was positively associated with reduced BMD (Exp (B) = 39.743, 95% confidence interval: 3.234-488.399, P = 0.004), and was specifically positively correlated with BMD values at three sites (r = 0.335 at right hip, r = 0.327 at left hip, r = 0.311 at lumbar spine). CONCLUSION Reduced BMD was found in the majority of ART-naive HIV-infected patients and BMI was identified as an additional risk factor for reduced BMD. Our results show that BMD reduction was simultaneously present in the left hip, right hip, and lumbar spine among nearly one fifth of patients. Our work highlights the importance of closely monitoring BMD in ART-naive patients and provides a foundation for the clinical intervention of bone demineralization in them.
Absorptiometry, Photon ; Adult ; Bone Density ; China/epidemiology* ; Cohort Studies ; HIV ; HIV Infections/drug therapy* ; Humans ; Lumbar Vertebrae ; Prevalence ; Risk Factors

ObjectiveThere are few studies on the correlation between the concentration of oncoembryonic antigen associated cell adhesion molecule 1(CEACAM1) and osteonecrosis of the femoral head (ONFH). The purpose of this study was to investigate the value of CEACAM1 in the early diagnosis of ONFH and the monitoring of the disease by detecting the CEACAM1 concentration in the serum of patients with ONFH and healthy subjects respectively.Methods95 patients, who were hospitalized and diagnosed as ONFH in the Department of No.3 Orthopaedic Ward, the First Affiliated Hospital of Guangzhou University of Chinese Medicine from May 2016 to November 2016, were selected as the experimental group. In addition, 56 genders and age-matched healthy subjects in our hospital were selected as the control group. The peripheral venous blood was taken and separated by a centrifuge. Their CEACAM1 concentrations were measured by enzyme linked immunosorbent assay (ELISA). The differences in CEACAM1 concentrations were analyzed between the two groups, and between patients with ONFH before (ARCO stage I or II) and after (ARCO stage III or IV) collapse as well.Results①The concentration of CEACAM1 in the experimental group was significantly lower than that in the control group [(6.11±2.07)ng/mL vs (7.21±3.76)ng/mL, P=0.022]. ②The concentration of CEACAM1 in Arco stage II[(7.33±1.90) ng/mL] was significantly higher than that in stage III [(6.08±2.26) ng/mL], P=0.037.③The difference of CEACAM1 concentration between before(stage II) and after collapse (stage III or stage IV) was statistically different [(7.33±1.90)ng/mL vs (5.86±2.02)ng/mL, P=0.007].④ROC curve analysis showed that the area under the curve was 0.710 (0.608-0.798), the sensitivity was 71.79%, the specificity was 58.82%, and the cut off value was ≤ 6.757ng/mL in the diagnosis of collapse of ONFH.ConclusionThe concentration of serum CEACAM1 can be used as a biochemical marker to assist in the diagnosis and monitoring of ONFH, which can provide reference for early diagnosis and monitoring of ONFH.

Objective To investigate the protective effect of recombinant adult serine protease inhibitor from Trichinella spiralis (TsadSPI) on sepsis-associated acute kidney injury in mice. Methods A total of 18 male BALB/c mice were randomly divided into the sham-operation group, the model group, and the TsadSPI treatment group, of 6 mice in each group. Sepsis-associated acute kidney injury was modeled in the model group and TsadSPI treatment group by cecal ligation puncture (CLP), while mice in the sham-operation group were only given exploratory laparotomy without ligation or perforation of the cecum. After 30 min of CLP, mice in the sham-operation group and the model group were intraperitoneally injected with PBS (100 μL), and mice in the TsadSPI treatment group were intraperitoneally injected with PBS (100 μL) containing TsadSPI (2 μg). At 12 h following modeling, the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (Cr) and urea nitrogen (BUN) were measured to assess the liver and kidney functions, and the changes of the mouse kidney structure were observed using HE staining. In addition, the serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10 and transforming growth factor (TGF)-β were measured using an enzyme-linked immunosorbent assay (ELISA), and the myeloid differentiation factor 88 (MyD88) and nuclear factor kappa-B (NF-κB) p65 expression was determined in kidney tissues using immunohistochemical staining. Results At 12 h following CLP, there were significant differences in the serum levels of ALT (F = 41.031, P < 0.001), AST (F = 54.757, P < 0.001), Cr (F = 24.142, P < 0.001) and BUN (F = 214.849, P < 0.001) among the three groups, and higher levels of ALT, AST, Cr and BUN were measured in model group than in the sham-operation group (P < 0.001), while lower ALT, AST, Cr and BUN levels were found in the TsadSPI treatment group than in the model group (P < 0.001). HE staining showed severe mouse kidney injuries following CLP, and TsadSPI treatment resulted in remarkable alleviation of the injury. ELISA measured significant differences in the TNF-α (F = 47.502, P < 0.001) and IL-6 levels (F = 222.061, P < 0.001) among the three groups, and showed a remarkable reduction in the TNF-α and IL-6 levels in the TsadSPI treatment group as compared to those in the model group (P < 0.001). In addition, there were significant differences in serum IL-10 (F = 16.227, P < 0.001) and TGF-β levels (F = 52.092, P < 0.001) among the three groups, and higher IL-10 and TGF-β levels were seen in the TsadSPI treatment group than in the model group (P < 0.001). Immunohistochemical staining showed greater MyD88 expression and a higher nuclear positive rate of NF-κB p65 in kidney tissues in the model group than in the TsadSPI treatment group. Conclusions TsadSPI may reduce the MyD88 expression and nuclear positive rate of NF-κB p65 in mouse kidney tissues to up-regulate the expression of immunomodulatory factors and down-regulate the expression of pro-inflammatory cytokines, thereby protecting sepsis-associated acute kidney injury.