BACKGROUND:The extracellular-regulated protein kinase 5(ERK5)signaling protein is essential for the survival of organisms,and resveratrol can promote osteoblast proliferation through various pathways.However,whether resveratrol can regulate osteoblast function through the ERK5 signaling protein needs further verification. OBJECTIVE:To explore the regulatory effect of ERK5 on the proliferation of MC3T3-E1 cells and related secreted proteins,and to further verify whether resveratrol can complete the above process by activating ERK5. METHODS:Mouse MC3T3-E1 preosteoblasts were treated with complete culture medium,XMD8-92(an ERK5 inhibitor),epidermal growth factor(an ERK5 activator),resveratrol alone,XMD8-92+EGF,and resveratrol+XMD8-92,respectively.Western blot assay was used to detect the expression of ERK5 and p-ERK5 proteins,proliferation-related proteins Cyclin D1,CDK4 and PCNA,and osteoblast-secreted proteins osteoprotegerin and receptor activator of nuclear factor-κB ligand in MC3T3-E1 cells of each group.The fluorescence intensity of ERK5,osteoprotegerin and receptor activator of nuclear factor-κB ligand in each group was detected by cell immunofluorescence staining,and cell proliferation was detected by EdU staining,respectively.The appropriate concentration and time of resveratrol intervention in MC3T3-E1 cells were determined by cell morphology observation and cell counting kit-8 assay. RESULTS AND CONCLUSION:The activation of ERK5 signaling protein could effectively promote the proliferation of MC3T3-E1 cells,up-regulate the osteoprotegerin/receptor activator of nuclear factor-κB ligand ratio.The appropriate concentration and time for resveratrol intervention in MC3T3-E1 cells was 5 μmol/L and 24 hours,respectively.Resveratrol could activate ERK5 signaling protein,thereby promoting osteoblast proliferation and up-regulating the osteoprotegerin/RANKL ratio.All these results indicate that resveratrol can promote the proliferation of MC3T3-E1 cells and up-regulate the osteoprotegerin/RANKL ratio by activating the ERK5 signaling protein.

Alzheimer's disease (AD) is the major form of dementia in the elderly and is closely related to the toxic effects of microglia sustained activation. In AD, sustained microglial activation triggers impaired synaptic pruning, neuroinflammation, neurotoxicity, and cognitive deficits. Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with regulating microglia function. Here, we use RNA sequencing to identify a deubiquitinase YOD1 as a regulator of microglial function and AD pathology. Further study showed that YOD1 knockout significantly improved the migration, phagocytosis, and inflammatory response of microglia, thereby improving the cognitive impairment of AD model mice. Through LC-MS/MS analysis combined with Co-IP, we found that Myosin heavy chain 9 (MYH9), a key regulator maintaining microglia homeostasis, is an interacting protein of YOD1. Mechanistically, YOD1 binds to MYH9 and maintains its stability by removing the K48 ubiquitin chain from MYH9, thereby mediating the microglia polarization signaling pathway to mediate microglia homeostasis. Taken together, our study reveals a specific role of microglial YOD1 in mediating microglia homeostasis and AD pathology, which provides a potential strategy for targeting microglia to treat AD.

BACKGROUND:Fluid shear stress plays an important role in osteoblast proliferation and apoptosis.However,whether Caveolin-1 is involved in the process of fluid shear stress-induced proliferation and apoptosis in osteoblasts is unknown. OBJECTIVE:To explore the role of Caveolin-1 in fluid shear stress-regulated osteoblast proliferation and apoptosis. METHODS:The MC3T3-E1 osteoblasts in good growth status were selected and loaded with fluid shear stress at an intensity of 1.2 Pa for different times(0,30,60,90 minutes).The expression of Caveolin-1 protein was observed and conditions with a time of 60 minutes were screened for the experiment.MC3T3-E1 cells were divided into control group,fluid shear stress group,fluid shear stress+pcDNA 3.1 group(control),fluid shear stress+pcDNA Cav-1 group(plasmid overexpression),and intervened with fluid shear stress and overexpression of Cav-1,respectively.The expression of molecules related to proliferation and apoptosis in MC3T3-E1 cells was detected by qRT-PCR and western blot.In addition,the proliferative activity of MC3T3-E1 cells was detected by cell counting kit-8 and EdU assay;and cell apoptosis was detected by Hoechst 33258 and flow cytometry. RESULTS AND CONCLUSION:The expression of Caveolin-1 in MC3T3-E1 cells was significantly down-regulated after loading fluid shear stress,and the expression level was lowest after 60 minutes.Overexpression of Caveolin-1 attenuated the proliferation-promoting and apoptosis-suppressing effects of fluid shear stress in MC3T3-E1 cells.In conclusion,Caveolin-1 has a vital role in fluid shear stress-regulated osteoblast proliferation and apoptosis,which may offer a potential therapeutic strategy for osteoporosis.

Objective:To explore the clinical features and genetic etiology of a patient with adult-onset globoid cell leukodystrophy/Krabbe disease (KD).Methods:A patient who was admitted to the Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology on February 15, 2022 due to exacerbation of right leg weakness for over 4 years was selected as the study subject. Clinical data and results of medical imaging and genetic analysis were analyzed. Candidate variants were verified by family analysis.Results:The patient, a 36-year-old woman, had spasmodic gait as the primary presentation. Cranial magnetic resonance imaging (MRI) revealed symmetrical abnormalities in the bilateral corticospinal tracts, and the activity of β-galactocerebrosidase (GALC) in her white blood cells was significantly decreased. The patient was found to harbor compound heterozygous variants of the GALC gene, namely c.461C>A (p.Pro154His) and c. 1901T>C (p.Leu634Ser). Her mother, sister and nephew were heterozygous carriers of the c. 461C>A (p.Pro154His) variant, whilst her father was heterozygous for the c.1901T>C (p.Leu634Ser) variant. Conclusion:The patient was ultimately diagnosed with adult-onset KD, for which the compound heterozygous variants of the GALC gene may be accountable.

The main function of anterior cruciate ligament (ACL) is to maintain stability of the knee joint and prevent anterior displacement of the tibial plateau. ACL injury accounts for more than 50% of the knee joint injuries. If not timely handled, it will increase the risk of secondary injuries to structures such as the meniscus and cartilage, causing chronic pain and degeneration of the knee joint. Although most ACL injuries can be determined by their direct signs on MRI, the identification of complex situations and partial tears of ACL are still not satisfactory, which subsequently affects treatment strategies. After ACL injury, changes in anatomical relationship of the knee joint can also lead to morphological changes in other structures such as the posterior cruciate ligament (PCL) on MRI, and these indirect signs can assist in the diagnosis of ACL injury. The authors reviewed the application of MRI-related indicators of PCL in diagnosing ACL injury, hoping to provide references and new ideas for clinical decision-making.

Objective:To investigate the value of ultrasonography in diagnosis of transposition of great arteries of the fetus at 11-13 + 6 weeks gestation. Methods:A prospective study was conducted on fetuses screened by ultrasound in the first trimester in Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region between January 2015 and March 2022. Fetal heart structure was screened by three-section screening method. Fetuses with suspected transposition of the great arteries at 11-13 + 6 weeks gestation underwent followed-up ultrasound examination, chromosome and gene test results. The ultrasound characteristics and prognosis pregnancy outcomes were summarized. Results:Twenty-one cases of transposition of the great arteries were detected by ultrasonography, including complete transposition of great arteries (20 cases) and congenitaly corrected transposition of the great arteries (1 case). Two cases were miss diagnosed. Twenty-one cases showed parallel signs of two major arteries on grayscale outflow section at 11-13 + 6 weeks gestation. There were 6 cases with aneuploid ultrasonographic soft markers abnormality, 2 cases with extracardiac malformation. Chromosome and microarray analysis were performed in 13 cases. 4 cases with chromosomal abnormality. Four cases of chromosomal abnormalities were associated with ultrasonographic soft markers abnormality, and 1 case with extracardiac malformation.In the 23 cases, 20 cases were induced, 1 miscarried, and 2 delivered to term. Among the fetuses delivered at term, 1 case died before neonatal operation and 1 case survived. Conclusions:Standardized ultrasound scan at 11-13 + 6 weeks has high accuracy in diagnosis of transposition of the great arteries. And the incidence of chromosomal abnormality is high with ultrasonographic soft markers abnormality or extracardiac malformation.

Objective:To investigate the effect of visceral obesity on the short-term curative effect of Da Vinci robotic-assisted radical resec-tion for rectal cancers.Methods:Clinical and pathological data of patients with rectal cancer undergoing Da Vinci robotic-assisted surgery,admitted to People's Hospital of Zhengzhou University and Cancer Hospital of Zhengzhou University from November 2019 to June 2022 were retrospectively analyzed.Visceral fat area(VFA)≥100 cm2 was used as the standard to define visceral obesity.Patients were categorized in-to visceral and non-visceral obesity groups.The short-term efficacy of the two groups was evaluated,and the influencing factors of post-operative complications were analyzed using univariate and multivariate Logistic regression.Results:Among a total of 169 patients,93 were included in the visceral obesity group and 76 in the non-visceral obesity group.There was no significant difference in the baseline data between the two groups(P>0.05).There was no conversion to laparotomy in the non-visceral obesity group,and the conversion rate was 1.1%(1/93)in the visceral obesity group.The second operation rate was 2.2%(2/93)in the visceral obesity group and 1.3%(1/76)in the non-visceral obesity group with no statistical difference between the two groups.There were no significant differences in the operation dur-ation,intraoperative blood loss,number of lymph node dissections,and total postoperative complication rate between the two groups(P>0.05).Multivariate Logistic regression analysis revealed that an NRS≥3 independently contributed as a risk factor for postoperative com-plications(OR=3.190,95%CI:1.240-8.210,P=0.016).Conclusions:An NRS≥3 is an independent risk factor for complications post-robotic rad-ical rectal cancer surgery.The robotic surgical platform can overcome obesity-related limitations and is equally safe and effective for pa-tients with visceral obesity presenting with rectal cancer.

Objective : To analyze the epidemiological characteristics and pathogen spectrum of hand，foot mouth disease (HFMD) in Anhui province from 2015 to 2022，and to provide scientific evidence for prevention and control measures of HFMD． Methods : The surveillance data of hand，foot and mouth disease in Anhui province from 2015 to 2022 were analyzed by descriptive epidemiology. Real-time PCR was used to detect and classify HFMD samples. Results : A total of 650 590 HFMD cases were reported in Anhui province from 2015 to 2022，including 1 406 se- vere cases and 17 deaths．The annual reported incidence was 131. 45 /100 000．The epidemic features of“low incidence in odd years and high incidence in even years”were presented from 2015 to 2019．The incidence showed a continuous decline from 2020 to 2022．The monthly distribution showed the characteristics of bimodal epidemic，and the main peak was not obvious in 2020．Hefei，Fuyang，Bozhou，Chuzhou and Suzhou ranked the top five cities in terms of cumulative incidence．The age of onset was mainly distributed in children aged 5 years and below，accounting for 89. 26% of the total cases．The male to female ratio was 1. 48 ∶ 1．A total of 28 657 laboratory-confirmed cases had been reported from 2015 to 2022．EV71 cases accounted for 10. 57% ，Cox A16 cases accounted for 24. 90% ，and other enterovirus cases accounted for 64. 53%．The dominant pathogens showed dynamic changes in different years．Since 2018，the proportion of EV71 decreased significantly，and the proportion of other enteroviruses gradually increased to become the dominant pathogens．Among other enteroviruses，Cox A6 strain was dominant (80. 48% ) ． Conclusion This study suggests that the prevention and control of HFMD in Anhui province should be paid more attention from April to July and from October to December．The focus areas are the cities in northern Anhui and Hefei where the floating population is large．The focus of prevention and control is on children aged 5 years and below．Other enteroviruses have become the dominant pathogens of hand-foot-mouth disease in Anhui province，Cox A6 strain is dominant.

Objective:To investigate the effect of low molecular weight heparin (LMWH) on the inflammatory response of PC12 cells induced by oxygen glucose deprivation (OGD) and its related mechanism.Methods:The PC12 cells were cultured in vitro were randomly divided into sham(control) group, OGD group, LMWH group and blocking agent group. The latter group was divided into six groups: Eritoran+ OGD group, LMWH+ Eritoran+ OGD group, ST2825+ OGD group, LMWH+ ST2825+ OGD group, pyrrolidinedithiocarbamate (PDTC)+ OGD group and LMWH+ PDTC+ OGD group. OGD cell model was established. Cell counting kit-8 (CCK-8) assay was used to detect cell activity. The expressions of toll-like receptor 4 (TLR4), MyD88 and nuclear factor κB (NF-κB) mRNA and protein were detected by real time polymerase chain reaction (qRT-PCR) and Western blot. The concentration of interleukin (IL)-1β, IL-6, tumor necrosis factor-α(TNF-α) and S100β were determined by enzyme linked immunosorbent assay (ELISA). Results:The cell activity of OGD group was significantly lower than that of control group on the first, second, third day ( P<0.05). Compared with OGD group, the activity of LMWH group was increased on the second, third day ( P<0.05), but lower than that of control group ( P<0.01). The mRNA expression of TLR4, MyD88 and NF-κB was significantly increased in OGD group compared with the control group ( F=144.9, F=710.5, 79.51, P<0.01). Compared with OGD group, the mRNA expression of TLR4, MyD88 and NF-κB were significantly decreased after treatment with LMWH ( P<0.01), and the specific inhibitor of TLR4, MyD88 and NF-κB enhanced the anti-inflammatory effect of LMWH. The protein expression of this pathway was consistent with that of the gene. The concentration of IL-1β, IL-6, TNF-α and S100β in OGD group was significantly higher than control group ( P<0.05). After treatment with LMWH, the concentrations of inflammatory factors and S100β were significantly decreased compared with OGD group ( P<0.01). When hinder TLR4, MyD88 and NF-κB respectively by Eritoran, ST2825 and PDTC, the concentrations of inflammatory factors and S100β were significantly decreased, but it was still higher than control group ( P<0.05). Conclusions:OGD can cause pathological damage of PC12 cells, including high expression level of S100β and aggravation of inflammatory reaction. LMWH can improve cell activity, down-regulate inflammatory reaction degree and protect the cells. Using inhibitors of TLR4/MyD88/NF-κB pathway to inhibit the corresponding target, the up-regulation of inflammatory factors by OGD can be inhibited in varying degrees. These suggested that LMWH may regulate inflammatory reaction of PC12 cells induced by OGD through TLR4/MyD88/NF-κB pathway.

Objective To explore the influence of modified radical gastrectomy on glycometabolism in patients with gastric carcinoma and non-obese T2DM.Methods The retrospective study was carried out to analyze the changes of glycometabolism between preoperative and postoperative follow-up in 25 patients with gastric carcinoma and non-obese T2DM.The above parameters included fasting plasma glucose (FPG),2-hour postprandial blood glucose (2 h PBG),glycosylated hemoglobin A1c (HbA1c),fasting insulin (FINS),homeostasis model assessment-insulin resistance (HOMA-IR),fasting glucagon-like peptide-1 (GLP-1),and glucose-dependent insulinotropic polypeptide (GIP).Results At the 6th and 12th month after operation,the related parameters such as FPG,2 h PBG,HbA1c,FINS and HOMA-IR were (7.54±1.44) mmo]/L and (7.17±1.35) mmol/L,(9.97±1.59)mmol/L and (9.47±1.23) mmol/L,(6.46±0.74)％ and (6.31±0.97)％,(7.73±0.98) μIU/ml and (7.44±0.96) μIU/ml,1.10±0.15 and 1.04±0.14 respectively.The above indexes were significantly improved compared with those before operation (P＜O.05).The levels of fasting GLP-1 at 6th and 12th month after operation were (2.27±0.25) pmol/ml and (2.33±0.27) pmol/ml respectively,and there was no significant change compared with those before operation (P＞0.05).On the contrary,the levels of GIP at 6th and 12th month after operation are significantly decreased compared with that before operation,which were (7.23±1.33) pmol/ml and (6.40±1.20) pmol/ml respectively.Conclusion The modified radical gastrectomy can improve T2DM in patients with gastric carcinoma markedly,even curing some patients,which may be related to the decrease of fasting GIP after operation.