ObjectiveTo observe the effect of bee acupuncture therapy on clinical symptoms and signs， as well as the level of inflammatory cytokine interleukin-6 （IL-6） in synovial fluid of patients with knee osteoarthritis. MethodsThe 94 patients with knee osteoarthritis were divided into the control group and the trial group by the random number table method， with 47 cases in each group. Both groups were given one tablet （60 mg） of etoricoxib orally every morning for 2 weeks. The control group also received microneedle shallow acupuncture therapy， once a day for 5 consecutive times followed 2-day pause， and continued 5 consecutive times， as a course of treatment； the trial group was treated with bee acupuncture therapy once every 2 days， 2 times a week， and 4 times as a course of treatment. Both groups have a course of treatment for 2 weeks. The changes in clinical symptoms and signs of patients in the two groups were observed and evaluated before treatment， after 1- and 2-week treatment， and 12-week follow-up and the differences in Lequesne index scores， HSS scores， Visual Analogue Scale （VAS） scores and IL-6 levels in knee synovial fluid between the two groups of patients were also compared. ResultsNo patients lost to follow up in either group. The Lequesne index scores and VAS scores were lower， and the HSS scores were higher in both groups at all time points after treatment compared with those before treatment （P＜0.05）. Compared at the same time after treatment， the Lequesne index scores and VAS scores of the trial group were lower than those of the control group， and the HSS scores were higher than those of the control group （P＜0.05）. IL-6 in synovial fluid was lower in the trial group at the 12-week follow-up than before treatment （P＜0.05）， but there was no significant difference between two groups at each time point（P＞0.05）. ConclusionBee acupuncture therapy for knee osteoarthritis can significantly improve clinical signs and symptoms， but has no significant effect on the level of IL-6 in knee synovial fluid.

Objective:To investigate alterations in the glymphatic system of spinocerebellar ataxia type 3 (SCA3) patients based on quantitative MRI, and its association with genetic information and motor dysfunction.Methods:The study was a cross-sectional study. This prospective study recruited 39 confirmed SCA3 patients (SCA3 group) and 40 matched healthy controls (HC group) who were seen at the Southwest Hospital of Army Medical University from May 2017 to June 2023. All subjects underwent cranial MRI scanning. Clinical assessments were conducted on all participants using the scale for the assessment and rating of ataxia (SARA) and the international cooperative ataxia rating scale (ICARS). The automatic segmentation and volume measurement of the choroid plexus based on Freesurfer 6.0; the perivascular interstitial space (PVS) was automatically segmented based on the deep-learning model VB-Net, and the volume of the PVS in each brain region was quantified after manual correction. Independent samples t-test and Mann-Whitney U-test were used to analyze the changes in the class lymphatic system in the SCA3 group and the HC group. Pearson partial correlation analysis was used to explore the relationship between CAG repeats, the glymphatic system, and motor dysfunction. Results:The standardized choroid plexus volume in the SCA3 group was (1.24±0.36)×10 3 mm 3, and that in the HC group was (0.96±0.34)×10 3 mm 3, with a statistically significant difference ( t=4.01, P<0.001). PVS volumes in the frontal lobe, temporal lobe, parietal lobe, basal ganglia, cerebellum, thalamus, and brainstem regions in the SCA3 group were significantly higher than those of HC group ( P<0.05). Partial correlation analysis revealed that CAG repeats in SCA3 group were positively correlated with SARA, ICARS, and basal ganglia PVS volumes ( r=0.65, 0.58, 0.29; P=0.001, 0.001, 0.042). Cerebellar and temporal lobe PVS volumes were positively correlated with SARA ( r=0.59, 0.47; P=0.001, 0.003), and positively correlated with ICARS scores ( r=0.61, 0.40; P=0.001, 0.011). Choroid plexus volume was positively correlated with cerebellar and basal ganglia PVS volumes ( r=0.41, 0.31; P=0.009, 0.043). Conclusions:The glymphatic system of SCA3 patients have significant alteration and have association with CAG repeats and motor dysfunction.

OBJECTIVE To study the effect and potential mechanism of eriodictyol on non-alcoholic fatty liver disease （NAFLD）. METHODS Sixteen C57BL/6J mice were randomly divided into control group， NAFLD model group， and eriodictyol low-dose and high-dose groups （50， 100 mg/kg）， with 4 mice in each group. Except for control group， the other groups were fed with high fat diet to induce NAFLD model. After four weeks of preprocessing， they were given relevant medicine intraperitoneally （0.01 mL/g）， once a day， for 6 consecutive weeks. The body weight and liver weight of mice were measured， and the pathological damage of liver tissue in mice was observed. The levels of aspartate aminotransferase （AST）， alanine aminotransferase（ALT）， and triglycerides （TG） in serum， as well as the protein expressions of nuclear factor-erythroid 2-related factor 2 （Nrf2） and heme oxygenase-1 （HO-1） in liver tissue were determined. In vitro NAFLD model was established by using 0.5 mmol/L oleic acid （OA） in HepG2 cells. Normal control group， NAFLD model group and eriodictyol low-， medium- and high-concentration groups （50， 100， 150 μmol/L） were set up. HepG2 cells in drug groups were treated with eriodictyol for 24 h at the time of modeling. The lipid deposition was observed in cells， and the levels of TG， malondialdehyde （MDA） and reactive oxygen species （ROS） as well as the phosphorylation levels of the mitogen-activated protein kinase （MAPK） signal pathway related proteins [extracellular signal-regulated kinase （ERK）， c- Jun N-terminal kinase （JNK）] and the protein expressions of Nrf2 and HO-1 were all determined. RESULTS In the in vivo experiment， compared with the NAFLD model group， the body weight， liver weight， the serum levels of AST， ALT and TG were all decreased significantly in eriodictyol low- and high-dose groups （except for serum level of AST in eriodictyol low-dose group） （P＜0.01）； liver lipid deposition was reduced significantly and the protein expressions of Nrf2 and HO-1 in liver tissues were further up-regulated （P＜0.01）. In the in vitro experiment， compared with the NAFLD model group， the lipid deposition in hepatocytes was reduced in eriodictyol low-， medium- and high-concentration groups （P＜0.01）， and the levels of ROS， MDA and TG were down-regulated （P＜0.05 or P＜0.01）； the phosphorylation levels of ERK and JNK were significantly down-regulated （P＜0.01）， while the protein expressions of Nrf2 and HO-1 were up-regulated significantly （P＜0.01）. CONCLUSIONS Eriodictyol can inhibit MAPK signaling pathway and activate Nrf2/HO-1 signaling pathway to alleviate NAFLD.

Although somatic cells can be reprogrammed to pluripotent stem cells (PSCs) with pure chemicals, authentic pluripotency of chemically induced pluripotent stem cells (CiPSCs) has never been achieved through tetraploid complementation assay. Spontaneous reprogramming of spermatogonial stem cells (SSCs) was another non-transgenic way to obtain PSCs, but this process lacks mechanistic explanation. Here, we reconstructed the trajectory of mouse SSC reprogramming and developed a five-chemical combination, boosting the reprogramming efficiency by nearly 80- to 100-folds. More importantly, chemical induced germline-derived PSCs (5C-gPSCs), but not gPSCs and chemical induced pluripotent stem cells, had authentic pluripotency, as determined by tetraploid complementation. Mechanistically, SSCs traversed through an inverted pathway of in vivo germ cell development, exhibiting the expression signatures and DNA methylation dynamics from spermatogonia to primordial germ cells and further to epiblasts. Besides, SSC-specific imprinting control regions switched from biallelic methylated states to monoallelic methylated states by imprinting demethylation and then re-methylation on one of the two alleles in 5C-gPSCs, which was apparently distinct with the imprinting reprogramming in vivo as DNA methylation simultaneously occurred on both alleles. Our work sheds light on the unique regulatory network underpinning SSC reprogramming, providing insights to understand generic mechanisms for cell-fate decision and epigenetic-related disorders in regenerative medicine.
Male ; Mice ; Animals ; Cellular Reprogramming/genetics* ; Tetraploidy ; Pluripotent Stem Cells/metabolism* ; Induced Pluripotent Stem Cells/metabolism* ; DNA Methylation ; Spermatogonia/metabolism* ; Germ Cells/metabolism*

Objective:To analyze risk factors for duration of small or medium-sized coronary artery aneurysms (CAA) in children with Kawasaki disease (KD) so as to provide clinical guidance for early and full course treatment.Methods:The clinical data of 68 children diagnosed with KD in the Department of Pediatrics, the First Affiliated Hospital of Xinxiang Medical University from January 2018 to January 2021 were retrospectively analyzed.According to duration of CAA, all cases were divided into 2 groups, duration of CAA ≥ 8 weeks group and duration of CAA <8 weeks group.Risk factors associated with CAA duration were screened using univariate analysis, and then independent risk factors for CAA duration in children with KD were analysed using multiple Logistic regression analysis. Results:A total of 68 cases were enrolled in this study.Among these cases, 45 cases (66.18%) were male and 23 cases (33.82%) were female.The onset age was from 3 months to 10 years old, and the median onset age was 1.59 (1.02-3.19). There were 31 cases in the group with CAA duration ≥8 weeks and 37 cases in the group with CAA duration <8 weeks.Univariate analysis showed that patients with the total fever course >10 days[45.16%(14/31 cases) vs.21.62%(8/37 cases)], time of treatment with intravenous immunoglobulin (IVIG)>10 days[54.84%(17/31 cases) vs.16.22%(6/37 cases)], platelet (PLT)>600×10 9/L[32.26%(10/31 cases) vs.10.81%(4/37 cases)], hypersensitive C-reactive protein (HsCRP) >100 mg/L[38.71%(12/31 cases) vs.13.51%(5/37 cases)] (all P<0.05 ) in the group with CAA duration ≥8 weeks were significantly more than those in the group with CAA duration <8 weeks.However, there were no significant differences in gender, age, type of KD, etiology evidence, hormone application, duration of fever before IVIG application, IVIG sensitivity, IVIG application way, urine leukocytes, white blood cells, hemoglobin, percent of neutrophilic granulocyte, erythrocyte sedimentation rate, glutamic-pyruvic transaminase between the 2 groups (all P>0.05). Multivariate Logistic regression analysis showed that the course of IVIG before application >10 days ( OR=6.589, 95% CI: 1.678-25.867, P=0.007)and HsCRP >100 mg/L ( OR=7.949, 95% CI: 1.947-32.461, P=0.004)were independent risk factors for predicting the duration of KD complicated with small and medium-sized CAA ≥8 weeks. Conclusions:The course of IVIG before application >10 days and HsCRP>100 mg/L are independent risk factors for KD complicated with small and medium-sized CAA lasting ≥8 weeks.

Objective To investigate the clinicopathological characteristics and independent risk factors of hepatocellular carcinoma (HCC) differentiation.  Methods A total of 108 HCC patients who underwent operation and treatment were reviewed and classified into low differentiation group (n= 29, 26.85%), medium differentiation group (n=53, 49.07%) and high differentiation group (n=26, 24.07%) according to pathological diagnosis. The clinicopathological characteristics and the expression levels of Ki67 and P53 in each group were compared and analyzed. Logistic regression model was used to analyze the risk factors for low differentiation of HCC.  Results The proportion of cirrhosis, the positive rate of P53 and Ki67 expression level in different degrees of HCC differentiation were statistically significant (P<0.05). However, there were no significant differences in age, sex, tumor diameter, and hepatitis virus infection or tumor involvement of liver capsule between groups (P>0.05). Multivariate logistic analysis showed that cirrhosis (OR=3.408), high expression of Ki67 (OR=11.113) and positive P53 (OR=9.711) were the main risk factors for poorly differentiated HCC.  Conclusion There are differences in clinical characteristics and expressions of Ki67 and P53 in HCC patients with different degrees of differentiation. Logistic regression analysis can identify clinicopathological risk factors affecting the degree of differentiation of HCC, which can provide criterion support for accurate diagnosis and prognostic treatment.

【Objective】 To investigate the effect of sinomenine hydrochloride （SH） on angiogenesis and the underlying mechanism in breast cancer. 【Methods】 The 4T1 orthotopic tumor model of breast cancer was utilized， and mice were treated with different dosage of SH to investigate the effect of SH on tumor growth. IHC staining of CD31 was used to evaluate angiogenesis within tumors under different treatment. ELISA was performed to measure the bFGF level within tumor extracellular fluid （TEF） and tumor cells to analyze the effect of SH on bFGF secretion and production. RT-qPCR was utilized to evaluate the effect of SH on the mRNA expression of bFGF in tumor cells. Kaplan-Meier Plotter was analyzed online to investigate the relationship between bFGF expression and the survival of patients with breast cancer. 【Results】 SH at 100 mg/kg could inhibit 4T1 orthotopic tumor growth compared with saline （P<0.05）， but SH showed little cytotoxicity in vitro under the tested concentrations. SH at 100 mg/kg suppressed the vessel area compared with saline （P<0.01）， and the concentration of angiogenic factor bFGF in TEF and tumor cells was decreased by SH treatment （P<0.05）， while the mRNA expression of bFGF in tumor cells was also downregulated by SH treatment （P<0.05）. Kaplan-Meier Plotter online analysis showed that elevated mRNA expression of bFGF in the primary tumor was associated with poorer OS， RFS and DMFS in patients with breast cancer （P<0.01）. 【Conclusion】 SH inhibits breast cancer growth by suppressing bFGF-induced angiogenesis， which enriches the pharmacological effects of this traditional Chinese medicine.

Objective:To detect the levels of cytokines in peripheral blood of patients with chronic immune thrombocytopenia (ITP) and analyze their significance in the clinical prognosis of children with chronic ITP.Methods:Thirty patients with chronic ITP who were treated in the Department of Pediatrics, the First Affiliated Hospital of Xinxiang Medical Univercity from October 2015 to October 2018 were followed and enrolled in the experimental group and 40 healthy children in the same hospital were enrolled in the healthy control group.The levels of interleukin-2(IL-2), interferon-γ(IFN-γ), tumor necrosis factor(TNF), interleukin-4(IL-4), interleukin-6(IL-6), interleukin-10(IL-10) and interleukin-17A(IL-17A) in the experimental group and the healthy control group were detected by flow cytometry (CBA). The relationship between cytokines and prognosis of children with chronic ITP were analyzed.Results:Thirty patients with ITP were enrolled. The expressions of IL-2 and IL-17A in the experimental group before treatment were (7.86±3.90) ng/L and (10.45±12.35) ng/L, while those of IL-2 and IL-17A in the healthy control group were (3.11±2.41) ng/L and (2.97±7.04) ng/L. The levels of IL-2 and IL-17A in the experimental group were significantly higher than those in the healthy control group, and the differences were statistically significant ( t=-7.123, -5.582, all P<0.01). The expressions of IL-4 and IL-10 in the experimental group before treatment were (0.38±0.25) ng/L and (1.80±1.25) ng/L, while those of IL-4 and IL-10 in the healthy control group were (3.08±0.26) ng/L and (4.55±3.44) ng/L. The levels of IL-4 and IL-10 in the experimental group were significantly lower than those in the healthy control group, and the differences were statistically significant ( t=8.400, 5.653, all P<0.01). The expressions of IL-6, TNF and IFN-γ in the experimental group before treatment were (7.30±9.16) ng/L, (4.85±7.60) ng/L and (7.68±20.41) ng/L, while those of IL-6, TNF and IFN-γ in the healthy control group were (5.44±4.18) ng/L, (1.97±0.37) ng/L, (4.81±17.71) ng/L. There was no significant difference between the two groups ( P>0.05), and no significant difference in the levels of cytokines between the patients with chronic ITP before and 12 months after treatment ( P>0.05). Conclusions:The changes of T lymphocyte related cytokines are closely related to the pathogenesis and development of chronic ITP in children. There may be persistent immune dysfunction in children with chronic ITP. Dynamic monitoring of cytokines IL-2, IL-4, IL-10, IL-17A, especially IL-17A, is helpful to judge the prognosis of ITP in children, and may be of guiding significance in evaluating clinical prognosis.

Objective: To investigate the physical properties of Ti-6Al-4V clasps generated by selective laser melting (SLM) with different construction directions and to compare these clasps with cast clasps, which could provide a basis for fabricating SLM clasps with high precision and excellent mechanical properties. Methods: Ti-6Al-4V clasps were fabricated by SLM at 0 degrees (SLM0 group), 45 degrees (SLM45 group) and 90 degrees (SLM90 group) (n = 12). Twelve clasps were cast by the casting method as the control group. Meanwhile, four metal abutments were cast randomly as the abutments of the four groups. X-ray was used to detect cracks in the clasps of each group. The roughness of the clasps was measured by confocal microscopy, the fitness tests between clasps and abutment were processed by stereomicroscopy, and the microstructure of clasps in each group was observed under a metallographic microscope to evaluate the physical properties. Results : There were 0-8 visible cracks in the casting group but no obvious defects in the SLM groups. The maximum surface roughness was observed in the cast group (18.102 ± 3.762) μm, while the minimum roughness was observed in the SLM90 group (5.942 ± 1.486) μm (P < 0.05). There was no statistically significant difference in surface roughness between the SLM0 group [(8.711 ± 2.378) μm] and the SLM45 group [(8.513 ± 1.161) μm]. Fitness was worst in the casting group [(68.445 ± 14.876) μm] and best in the SLM90 group [(33.417 ± 5.880) μm] (P < 0.05). There was no statistically significant difference in fitness between the SLM0 group [(52.917 ± 12.102) μm] and the SLM45 group [(50.889 ± 7.011) μm]. In addition, the growth direction of the β grains was roughly parallel to the build direction, and acicular α grains were present between β grains. SLM was composed of fine grains, while the cast group had large grains. Conclusions Specimens generated by SLM had finer grains than cast specimens. In addition, SLM90 clasps had the highest fitness and the lowest surface roughness.

Brexanolone, also known as 3a, 5a-tetrahydroprogesterone, is a metabolite of progesterone and an important neuroactive steroid with a wide range of biological activities.Recently, the most exciting thing is that 2019 year the FDA has approved its treatment of postpartum depression, which is also the only drug to obtain indications for postpartum depression.It is expected to officially enter the market by the end of June 2019 year.This article reviews the research progress of its pharmacological action.