To summarize the distribution characteristics of human papillomavirus(HPV) infection types in patients with cervical squamous intraepithelial lesion(SIL) and cervical cancer(CC), and to explore the impact of HPV vaccination, HPV infection types, and general clinical data on different grades of cervical lesions.

Objective:To analyze the influence factors of urinary tract infection after transurethral bipolar plasma enucleation of the prostate (TUPEP) in patients with benign prostatic hyperplasia(BPH), and the early predictive value of serum inflammatory indicators for postoperative urinary tract infection.Methods:A total of 300 patients with BPH who received TUPEP treatment in the Department of Urology, Kailuan General Hospital from January 2021 to August 2023 were selected, according to whether they had urinary tract infections after the operation, they were divided into infection group ( n=117) and non-infection group ( n=183). The clinical data of the two groups were collected, and the serum inflammatory indexes of the two groups were recorded within 24 hours after the operation, including white blood cell count (WBC), neutrophil granulocyte (NE%), high-sensitivity C-reactive protein (hs-CRP), serum amyloid A (SAA), procalcitonin (PCT), heparin-binding protein (HBP), interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and serum ferritin (SF). The differences of clinical data and serum inflammatory indexes between the two groups were analyzed. The measurement data of normal distribution were expressed as mean ± standard deviation ( ± s), and independent sample t-test was used for inter-group comparisons. The measurement data of non- normal distribution were represented by median (interquartile range) [ M ( Q1, Q3)], and the Mann-Whitney U test was used for inter-group comparison. The count data were expressed as cases and percentage, and inter-group comparisons were conducted using the Chi-test. Multivariate Logistic regression analysis was used to explored the influencing factors of urinary tract infections in BPH patients after TUPEP surgery. The receiver operating characteristic (ROC) curve was plotted using GraphPad Prism 8.0.1 medical plotting softwar to evaluate the predictive value of serum inflammatory markers and combined detection of multiple markers for early postoperative urinary tract infections. Results:The duration of disease, history of diabetes, international prostate symptom score (IPSS), prostate volume, preoperative serum prostate-specific antigen (PSA) level, preoperative urine residual volume, operation time, intraoperative blood loss, postoperative catheter indwelling time, and hospitalization time in the infection group were higher than those in the non-infection group ( P<0.05). The preoperative 25-hydroxyvitamin D (25OHD) level and maximum urinary flow rate were lower in the infection group than those in the non- infection group ( P<0.05). Multivariate Logistic regression analysis showed that the course of the disease, history of diabetes, IPSS score, prostate volume, preoperative PSA level, preoperative urine residual volume, operation time, intraoperative blood loss, postoperative catheter indwelling time was positively correlated with urinary tract infection after TUPEP ( B=0.660, 0.242, 0.164, 0.125, 0.230, 0.066, 0.382, 0.022, 0.436, P<0.01), and preoperative 25OHD level and preoperative maximum urinary flow rate were negatively correlated with urinary tract infection after TUPEP ( B=-0.216, -0.372, P<0.01). The levels of hs-CRP, SAA, PCT, HBP, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, IFN-γ, SF in the infection group were higher than those in the non-infection group ( P<0.001). The ROC curve analysis showed that the area under the curve (AUC) of hs-CRP, SAA, PCT, HBP, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, IFN-γ, SF in early predicting urinary tract infection after TUPEP in BPH patients were 0.697, 0.775, 0.902, 0.873, 0.884, 0.904, 0.917, 0.823, 0.906, 0.852, 0.807, 0.787. The AUC of the combined detection of multiple serum inflammatory markers was 0.972, the sensitivity and specificity were 93.18% and 96.63%, and the sensitivity and specificity of the combined detection of multiple serum inflammatory markers were higher than those of separate detection. Conclusion:The course of BPH, whether to combine history of diabetes, preoperative IPSS score, prostate volume, preoperative PSA level, preoperative 25OHD level, preoperative maximum urinary flow rate, operation time, intraoperative blood loss, and postoperative catheter indwelling time are influencing factors of urinary tract infection after TUPEP, hs-CRP, SAA, PCT, HBP, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, IFN-γ, SF had certain value in the early prediction of urinary tract infection after TUPEP in patients with BPH, the combination of multiple indicators can improve the predictive value of early urinary tract infection.

Objective To explore the characteristics and mechanism of phase separation between TAR DNA binding protein-43(TDP-43)and ubiquitin.Methods The TARDBP gene and its truncated genes were inserted into vectors to construct recombinant plasmids for expression and protein purification.The phase separation system of ubiquitin and TDP-43 was constructed in vitro.The characteristics of the droplets formed via liquid-liquid phase separation were observed by fluorescence microscopy.The plasmids of ubiquitin and TDP-43 were co-transfected into HEK293T cells to observe aggregates containing TDP-43 and ubiquitin and find out whether TDP-43 could be ubiquitinated.Results The GFP-8Ub,TDP-43 full-length(FL)and truncated proteins were purified.TDP-43 FL and C-terminal domain(CTD)proteins were able to form droplets via phase separation with ubiquitin.The droplets changed into solid-like aggregates after prolonged incubation.Insolvable aggregates containing TDP-43 and ubiquitin were formed.TDP-43 was ubiquitinated under stress conditions in HEK293T cells after being co-transfected with ubiquitin and TDP-43 recombinant plasmids.Conclusion TDP-43 undergoes co-phase separation with ubiquitin,mainly driven by the multivalent interaction between TDP-43′s CTD structural domain and ubiquitin.The droplets finally form aggregates with solid-like properties.Under stress conditions,especially when the protein homeostasis is disrupted,TDP-43 and ubiquitin form aggregates while TDP-43 is ubiquitinated.This study reveals the basic mechanism of TDP-43 co-phase separation with ubiquitin and liquid-solid transformation.

Objective:To explore the expression relationship and significance of long chain non-coding RNA nuclear-enriched abundant transcript 1(LncRNA NEAT1)and miR-27a-3p in serum and cerebro-spinal fluid of patients with Alzheimer disease(AD).Methods:Sixty-six AD patients received by the department of neurology of our hospital from October 2019 to September 2021 were gathered,according to the clinical dementia rating scale score,they were grouped into mild group(≤ 1 point,n=41)and moderate-to-severe group(＞1 point,n=25).Another 66 cases of serum and cerebrospinal fluid sam-ples from outpatient physical examination personnel were regarded as the control group.The general infor-mation on all subjects was recorded and cognition was assessed;real-time quantitative PCR was performed to measure the expression levels of miR-27a-3p and NEAT1 in serum and cerebrospinal fluid;enzyme-linked immunosorbent assay was performed to measure the protein levels of β-amyloid precursor protein cleaving enzyme 1(BACE1),β-amyloid(Aβ)40 and Aβ42 in cerebrospinal fluid;Spearman's method was performed to analyze the correlation of serum miR-27a-3p and NEAT1 levels with mini-mental state examination(MMSE)and montreal cognitive assessment(MoCA)scores;Pearson method was per-formed to analyze the correlation between serum miR-27a-3p and NEAT1 levels and Aβ deposition standard uptake value ratio(SUVR)and cerebrospinal fluid miR-27a-3p,NEAT1,BACE1,Aβ42 and Aβ40 levels.Results:The MMSE score[21(17,25),9(7,11)vs.27(21,34)],MoCA score[17(12,21),10(7,13)vs.27(21,31)],serum miR-27a-3p level(0.55±0.13,0.46±0.06 vs.0.97± 0.22),cerebrospinal fluid miR-27a-3p(0.48±0.10,0.35±0.10 vs.1.03±0.31),Aβ42 levels[(303.55±36.77)ng/L,(231.45±34.14)ng/L vs.(499.99±53.63)ng/L]and Aβ42/Aβ40 ra-tio(0.030±0.008,0.022±0.007 vs.0.048±0.010)of AD patients in mild group and moderate-to-severe group were all lower than those in the control group,and the moderate-to-severe group were lower than the mild group(all P＜0.05);the serum NEAT1 level(2.31±0.64,3.13±0.76 vs.1.05± 0.20),SUVR(1.50±0.29,1.76±0.52 vs.0.74±0.15),and cerebrospinal fluid NEAT1(3.51± 1.24,4.30±1.65 vs.1.01±0.23)and B ACE 1 levels[(55.78±5.98)μg/L,(72.32±16.08)μg/L vs.(21.39±3.73)μg/L]were higher than those in the control group,and the moderate-to-se-vere group were higher than the mild group(all P＜0.05).Serum NEAT1 level in AD patients was posi-tively correlated with SUVR,cerebrospinal fluid NEAT1 and BACE1(r=0.350,0.606,0.341,P＜0.05),and negatively correlated with MMSE score and MoCA score(r=-0.473,-0.482,all P＜0.05);serum miR-27a-3p level was positively correlated with cerebrospinal fluid miR-27a-3p level,MMSE score and MoCA score(r=0.695,0.424,0.412,all P＜0.05),and negatively correlated with SUVR and cerebrospinal fluid BACE1 level(r=-0.521,-0.447,all P＜0.05).Conclusion:The expression trends of NEAT1 and miR-27a-3p in the serum and cerebrospinal fluid of AD patients are con-sistent,the level of NEAT1 is increased,and the level of miR-27a-3p is decreased.The levels of the two are negatively correlated,which is related to the degree of Aβ deposition in the brain of AD patients and is involved in the progression of AD.

Objective:To compare the effect of a 3D-printed ankle and foot orthosis (AFO) with that of a traditional AFO on the recovery of walking function after a stroke.Methods:Thirty-four hemiplegic stroke survivors were randomly divided into an observation group and a control group, each of 17. Both groups were taught good limb placement and given joint mobility, standing and walking training for 4 weeks wearing either a 3D-printed or a conventional AFO. Walking speed, walking endurance, and dynamic balance were evaluated before and after the experiment using the 10-metre walk test (10MWT), the 6-minute walk test (6MWT), and the timed up and go test (TUGT). Integrated electromyography (iEMG) was also performed on each subject′s bilateral rectus femoris, anterior tibialis, and gastrocnemius muscles during walking, and their healthy and affected side iEMG results were compared to assess the activation of the affected lower limb muscles.Results:After treatment, the 10MWT, 6MWT, and TUGT results of both groups had improved significantly, but the observation group′s average results were then significantly better than those in the control group. The iEMG disparities between the healthy and affected sides had also decreased significantly, but on average the disparities in the observation group were significantly smaller than in the control group.Conclusion:Both types of AFO can effectively improve the walking speed, walking endurance, and dynamic balance of hemiplegic stroke survivors and promote muscle activation in the affected lower limb. A 3D-printed AFO is relatively more effective.

Objective:To explore the effect of cathepsin L (CTSL) inhibitor on apoptosis of retinal pigment epithelial (RPE) cells and mitochondrial oxidative stress.Methods:RPE cells were cultured in vitro and divided into control group, hydrogen peroxide (H 2O 2) group, and H 2O 2+CTSL inhibitor group. The cells of H 2O 2 group and H 2O 2+CTSL inhibitor group were incubated in the medium containing 400 μmol/L H 2O 2 for 24 hours and 10 μmol/L CTSL inhibitor was added in H 2O 2+CTSL inhibitor group at the same time. The cells of normal group were routinely cultured cells. The follow-up experiment was carried out 24 hours after modeling. The rate of apoptosis was detected by flow cytometry. The expression of CTSL was detected by immunofluorescence staining, Western blot and real time-polymerase chain reaction. The level of mitochondrial super oxide was detected by MitoSOX fluorescent probe, and the mitochondrial structure was observed after MitoTracker staining, the average area, form factors, and branch of mitochondria were quantitatively analyzed. The two groups were compared using two-tailed Student t test, while numerous groups were compared using one-way ANOVA. Results:Compared with control group, the rate of apoptosis in H 2O 2 group was significantly higher ( t=3.307, P=0.029 7), the expression level of CTSL was significantly increased ( t=19.950, 6.916, 14.220; P<0.05). Compared with H 2O 2 group, the expression level of CTSL, the rate of apoptosis and the mitochondrial ROS level in H 2O 2+CTSL inhibitor group were significantly lower ( t=11.940, 4.718, 16.680; P<0.05). The mitochondria of H 2O 2+CTSL inhibitor group were elongated, oval-shaped or rod-shaped, while the mitochondria of H 2O 2 group lost their continuous contour shape and complete structure. The differences of the average area, form factors, and brach of mitochondria among 4 groups were statistically significant ( F=251.700, 34.010, 60.500; P<0.000 1). Conclusions:H 2O 2 can significantly induce apoptosis in RPE cells and increase CTSL expression. CTSL inhibitor can inhibit the H 2O 2-induced apoptosis of RPE cells, lower the mitochondrial super oxide level, and successfully repair the mitochondrial structure.

Objective:To explore the efficacy and safety of domestic bortezomib in combination with lenalidomide and dexamethasone in the treatment of newly diagnosed multiple myeloma (NDMM) .Methods:This multicenter, prospective, single-arm clinical study included 126 patients with NDMM admitted to seven hospitals between December 2019 and January 2022. All patients received domestic bortezomib in combination with lenalidomide and dexamethasone (BLD regimen), and the efficacy, prognostic factors, and safety were analyzed.Results:Among the 126 patients with NDMM, 118 completed four cycles of treatment, with an overall response rate (ORR) of 93.22% (110/118) and a ≥very good partial response (VGPR) rate of 68.64% (81/118). Ultimately, 114 patients completed at least eight cycles of treatment, with an ORR of 92.98% (106/114) and a ≥VGPR rate of 77.19% (88/114). Eighteen patients underwent autologous hematopoietic stem cell transplantation after completing 6-8 cycles of the BLD regimen, with an ORR of 100% (18/18) and a ≥VGPR rate of 88.9% (16/18). The proportion of patients achieving ≥VGPR increased with the treatment duration, and factors such as staging and age did not significantly affect efficacy. Single-factor analysis showed that R2-ISS stage Ⅲ/Ⅳ, blood calcium >2.27 mmol/L, and failure to achieve VGPR after six cycles were adverse prognostic factors for progression-free survival (PFS) ( P<0.05), whereas failure to achieve VGPR after six cycles was an adverse prognostic factor for overall survival (OS) ( P<0.001). Multifactor analysis demonstrated that failure to achieve VGPR after six cycles is an independent adverse prognostic factor for PFS ( P=0.002). The incidence of hematologic adverse reactions was 16.7% (19/114), and nonhematologic adverse reactions were mainly mild to moderate, with no significant cardiac or renal adverse reactions observed. Conclusion:The BLD regimen is effective in treating NDMM, in which patients with high-risk genetic features are still achieving a high ≥VGPR rate, and the overall safety is good.

Objective To explore the role of β-1,3-galactosyltransferase 2(B3galt2)in mice with cerebral ischemic injury.Methods Adult male C57BL/6J mice were randomly divided into the sham,suture-occluded middle cerebral artery occlusion(MCAO)model,MCAO model+lentiviral vector control(LV-GFP),and MCAO model+lentiviral vector overexpression B3galt2(LV-B3galt2)groups,with six mice in each group.Neurological deficit scoring and rotating rod experiments were performed 24 h after ischemia in each group,and 2,3,5-triphenyltetrazolium chloride(TTC)staining was used to determine the infarction volume.The number of neurons in the ischemic cerebral cortex was determined in each group using Nissl staining.The levels of oxidative stress-related factors in the brain tissues were detected using the relevant kits.Results Compared with the sham group,the MCAO model group showed increased infarct volume and neurological deficits(P<0.05),significantly decreased number of neurons in the ischemic cerebral cortex and levels of super-oxide dismutase(SOD)and glutathione peroxidase(GSH)(all P<0.05),and significantly increased levels of reactive oxygen species(ROS)and malondialdehyde(MDA)(all P<0.05).Compared with the MCAO model group,the LV-B3galt2 group had reduced volume of cerebral infarction,significantly improved neurological deficits(all P<0.05),significantly increased number of neurons in the ischemic cerebral cortex of mice,significantly decreased levels of ROS and MDA(P<0.05),and significantly elevated levels of SOD and GSH(all P<0.05).Conclusion B3galt2 overexpression can reduce brain injury in an ischemic damage mouse model,and its mechanism may be through the inhibition of oxidative stress reactions.

Objective The purpose of this study was to investigate how miR-200b-3p inhibitors the proliferation and metastasis of endometrial cancer(EC) cells by inducing the expression of FOS-like antigen 2(FOSL2) of activator protein 1(AP1) transcription family. Methods Endometrial cancer cell line HEC-1-A was divided into 12 groups: NC-mimic (transfected with negative control NC mimic), miR-200b-3p mimic (transfected with miR-200b-3p mimic), NC-inhibitor (transfected with negative control NC inhibitor), miR-200b-3p inhibitor group (transfected with miR-200b-3p inhibitor), si-NC (transfected with negative control Si-NC), si-FOSL2 (transfected with si-FOSL2), oe-NC (transfected with negative control oe-NC), oe-FOSL2 group (oe-FOSL2), miR-200b-3p mimic+oe-NC group (co-transfected with miR-200b-3p mimic and oe-NC), miR-200b-3p mimic+oe-FOSL2 group (co-transfected with miR-200b-3p mimic and oe-FOSL2), miR-200b-3p inhibitor+si-NC group (co-transfected with miR-200b-3p inhibitor and si-NC), miR-200b-3p inhibitor+si-FOSL2 group (co-transfected with miR-200b-3p inhibitor and si-FOSL2). Real-time fluorescence quantitative PCR, Western blot, CCK-8 assay, scratch test and Transwell assay were used to detect the expression of miR-200b-3p mRNA, FOSL2 mRNA and protein expression level, cell proliferation, migration and invasion. Results In endometrial cancer cell lines, the expression of miR-200b-3p was significantly down-regulated, while the expression of FOSL2 was significantly up-regulated. Compared with NC-mimic group, the expression of FOSL2, N-cadherin and Vimentin in miR-200b-3p mimic group was significantly decreased, and the expression of E-cadherin was significantly increased. The cell proliferation, migration rate and the number of transmembrane cells were significantly decreased. Compared with the miR-200b-3p mimic+oe-NC group, the expression of FOSL2, N-cadherin and Vimentin in miR-200b-3p mimic+oe-FOSL2 group was significantly increased, and the expression level of E-cadherin was significantly decreased, and the cell proliferation, migration rate and the number of transmembrane cells were significantly increased. Compared with NC-inhibitor group, the expression of FOSL2, N-cadherin and Vimentin in miR-200b-3p inhibitor group was significantly increased, and the expression of E-cadherin was significantly decreased. The cell proliferation, migration rate and the number of transmembrane cells were significantly increased. Compared with the miR-200b-3p inhibitor+si-NC group, the expression of FOSL2, N-cadherin and Vimentin in miR-200b-3p inhibitor+si-FOSL2 group was significantly decreased, and the expression of E-cadherin was significantly increased; the cell proliferation, migration rate and the number of transmembrane cells were significantly decreased. Conclusion The expression of miR-200b-3p in endometrial cancer cells is down-regulated, which can inhibitor the proliferation, migration and invasion of endometrial cancer cells by regulating the EMT process, and its mechanism is related to its targeted negative regulation of FOSL2 expression.
Humans ; Female ; Cell Proliferation/drug effects* ; MicroRNAs/genetics* ; Cell Line, Tumor ; Fos-Related Antigen-2/metabolism* ; Endometrial Neoplasms/metabolism* ; Neoplasm Metastasis/genetics* ; Cell Movement/drug effects* ; Gene Expression Regulation, Neoplastic ; Cadherins/metabolism*