BACKGROUND:Rev-erbα is involved in the regulation of inflammation,but pharmacological activation of Rev-erbα increases the risk for cardiovascular diseases.To reduce the relevant risk,an exploration on SR9009,a Rev-erbα agonist,combined with other drugs to relieve inflammation in skeletal myoblasts was conducted,laying the theoretical foundation for the treatment of inflammation-associated skeletal muscle atrophy. OBJECTIVE:To investigate the relationship of SR9009,indolepropionic acid and nuclear factor-κB signaling pathways in lipopolysaccharide-induced C2C12 myoblasts. METHODS:(1)C2C12 myoblasts were induced to differentiate in the presence of lipopolysaccharide(1 μg/mL).RNA-seq and KEGG pathway analysis were used to study signaling pathways.(2)C2C12 myoblast viability was assessed using the cell counting kit-8 assay to determine optimal concentrations of indolepropionic acid.Subsequently,cells were categorized into control group,lipopolysaccharide(1 μg/mL)group,SR9009(10 μmol/L)+lipopolysaccharide group,indolepropionic acid(80μmol/L)+lipopolysaccharide group,and SR9009+indolepropionic acid+lipopolysaccharide group.ELISA was employed to measure protein expression levels of interleukin-6 in the cultured supernatant.Real-time quantitative PCR were employed to measure mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Western blot assay were employed to measure protein expression levels of NF-κB p65 and p-NF-κB p65.(3)After Rev-erbα was knocked down by siRNA,knockdown efficiency was assessed by RT-qPCR.And mRNA levels of interleukin-6 and tumor necrosis factor α were also measured. RESULTS AND CONCLUSION:Compared with the blank control group,lipopolysaccharide time-dependently inhibited myofibroblast fusion to form myotubes,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were elevated,and the level of interleukin-6 in the cell supernatant was significantly increased.The results of KEGG pathway showed that the nuclear factor-κB signaling pathway was activated by lipopolysaccharide.Indolepropionic acid exhibited significant suppression of C2C12 myoblasts viability when its concentration exceeded 80 μmol/L.Indolepropionic acid and SR9009 inhibited the activation of NF-κB signaling pathway,thereby played an anti-inflammatory role,and suppressed the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Compared with the lipopolysaccharide group,the ratio of p-NF-κB p65/NF-κB p65 protein expression were downregulated.SR9009 combined with indolepropionic acid notably reduced lipopolysaccharide-induced inflammation,further downregulated the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.The ratio of p-NF-κB p65/NF-κB p65 protein expression was significantly lower than that in the SR9009+lipopolysaccharide group or indolepropionic acid+lipopolysaccharide group.Rev-erbα increases time-dependently with lipopolysaccharide induction.The knockdown efficiency of Rev-erbα by siRNA reached over 58%,and lipopolysaccharide was added after Rev-erbα was successfully knocked down.Compared with the lipopolysaccharide group,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were significantly up-regulated.These results conclude that Rev-erbα may act as a promising pharmacological target to reduce inflammation.SR9009 targeted activation of Rev-erbα combined with indolepropionic acid significantly inhibits the nuclear factor-κB signaling pathway and attenuates the inflammatory response of C2C12 myofibroblasts.Moreover,the combined anti-inflammatory effect is superior to that of the intervention alone.

A major impedance to neuronal regeneration after peripheral nerve injury(PNI)is the activation of various programmed cell death mechanisms in the dorsal root ganglion.Ferroptosis is a form of pro-grammed cell death distinguished by imbalance in iron and thiol metabolism,leading to lethal lipid peroxidation.However,the molecular mechanisms of ferroptosis in the context of PNI and nerve regeneration remain unclear.Ferroportin(Fpn),the only known mammalian nonheme iron export protein,plays a pivotal part in inhibiting ferroptosis by maintaining intracellular iron homeostasis.Here,we explored in vitro and in vivo the involvement of Fpn in neuronal ferroptosis.We first delineated that reactive oxygen species at the injury site induces neuronal ferroptosis by increasing intracellular iron via accelerated UBA52-driven ubiquitination and degradation of Fpn,and stimulation of lipid peroxidation.Early administration of the potent arterial vasodilator,hydralazine(HYD),decreases the ubiquitination of Fpn after PNI by binding to UBA52,leading to suppression of neuronal cell death and significant ac-celeration of axon regeneration and motor function recovery.HYD targeting of ferroptosis is a promising strategy for clinical management of PNI.

Objective:To explore the acupoint selection law in acupuncture and moxibustion in treating postpartum incontinence by using data mining technology.Methods:The clinical research literature on acupuncture and moxibustion treatment for postpartum incontinence was retrieved from CNKI, Wanfang Data, VIP, CBM, China Medical Journal Full-text Database, PubMed, Embase, Web of Science from the establishment of the databases to February 1, 2023. The acupoint prescription database was established using Excel 2016 and conducting frequency statistics of acupoints, meridians and specific acupoints. Clustering analysis was performed using SPSS Statistics 25.0, and association rule analysis was performed using SPSS Modeler 18.0.Results:A total of 70 articles were included, involving 70 acupuncture prescriptions and including 31 acupoints with a total frequency of 384 times. The top five acupoints were Sanyinjiao (SP6, 46 times), Guanyuan (CV4, 45 times), Zusanli (ST36, 43 times), Zhongji (RN3, 41 times), and Qihai (CV6, 38 times). The commonly used meridians were Conception Vessel, bladder meridian and spleen meridian. The involved acupoints were mostly located in the lower limbs and belly, and most of them were Jiaohui, Mu and Wushu acupoints. Five effective clustering groups were obtained by clustering analysis of high frequency acupoints. The core acupoint combination of association rules was Sanyinjiao (SP6)-Zusanli (ST36)-Guanyuan (CV4)-Qihai (CV6)-Zhongji (RN3).Conclusions:The pathogenesis of postpartum urinary incontinence is mainly characterized by qi deficiency. Acupuncture and moxibustion treatment of postpartum urinary incontinence follows the principles of invigorating qi and tonifying spleen, nourishing lung and tonifying kidney, paying attention to the use of acupoints in abdomen and lower limbs, and using the methods of upper and lower acupoints, anterior and posterior acupoints.

Objective:To investigate the clinical application of multi-oil fat emulsion (SMOF) in preterm infants with necrotizing enterocolitis (NEC).Methods:Preterm infants with NEC admitted to the Neonatal Intensive Care Unit in our hospital between January 2017 and December 2022 were retrospectively included. According to the type of fat emulsion used, they were divided into SMOF group and medium and long chain triglycerides (MCT/LCT) group. The data of two groups were compared and analyzed.Results:A total of 69 preterm infants were included, 34 in the SMOF group and 35 in the MCT/LCT group. There were no significant differences between the two groups in the levels of total bilirubin, indirect bilirubin, direct bilirubin, bile acid and γ-glutamyl transferase ( P>0.05). There were no significant differences between the two groups in triglyceride, low density lipoprotein and total cholesterol ( P>0.05). There were no significant differences between the two groups in the C reactive protein level, procalcitonin level, and the time to normal C reactive protein ( P>0.05). There were no significant differences in incidence of complications between the two groups, including parenteral nutrition-related cholestasis, bronchopulmonary dysplasia, retinopathy of prematurity, and brain injury ( P>0.05). Conclusions:Compared with MCT/LCT, the application of SMOF did not show significant effect on liver function, inflammation, or incidence of complications (parenteral nutrition-related cholestasis, bronchopulmonary dysplasia and retinopathy of prematurity) in preterm infants with NEC. Multi-center studies with larger sample size are needed for further investigation.

Objective:To screen mutations of the adenosine triphosphate(ATP)-binding cassette transporter A3(ABCA3)gene in elderly Chinese individuals with lung interstitial diseases(ILDs)and to analyze the clinical characteristics of ILDs in elderly patients.Methods:A prospective study, After further image analysis of patients diagnosed with interstitial lung diseases between September 2015 and December 2018 at the Department of Respiratory and Critical Care Medicine, the Second Xiangya Hospital of Central South University, 103 patients were willing to provide peripheral blood samples and signed informed consent.DNA samples were extracted and whole exome sequencing was performed to screen ABCA3 gene mutations.Clinical data of patients were summarized and analyzed.Results:Seven rare variants of the ABCA3 gene were identified in 6 patients, with a mean age of 67 years(69-73 years)and an equal sex distribution, and 33.3%(2/6)were smokers.The most notable presentation was diffuse lung lesions.Patients' final diagnoses included idiopathic pulmonary fibrosis(IPF, 3/6), nonspecific interstitial pneumonia(NSIP, 1/6), and IgG4-related lung disease(2/6). Meanwhile, compound heterozygous mutations of the ABCA3 gene responsible for IPF were identified in patient No.39, including p. Asp1465Asn, p.Leu3Vval and p. Val93Ile3, a new finding in patients with ILDs.Conclusions:ABCA3 mutation-related lung interstitial diseases exhibit variable characteristics, with differences in the age of onset, clinical manifestations, imaging features and prognosis between patients.ABCA3 mutations responsible for early-onset ILDs are mostly homozygous or compound heterozygous and usually highly pathogenic nonsense mutations.In contrast, ABCA3 mutations identified in elderly patients with ILDs are often missense mutations, a possible explanation for the variability of ILDs in the elderly.Since patients with ILDs caused by ABCA3 variants respond poorly to currently available treatment options, early genetic diagnosis may benefit patients by enhancing disease awareness.

Objective:To investigate correlations between blood lipid levels and clinical characteristics of patients with psoriasis vulgaris (PsV) in Fujian province.Methods:Totally, 245 PsV patients were enrolled from Department of Dermatology of the First Affiliated Hospital of Fujian Medical University from March 2019 to March 2022, and 250 gender-, age-, and body mass index-matched health checkup examinees served as controls. Their biochemical indicators, such as blood lipids, liver function, and kidney function, were evaluated. Clinical data, such as disease courses, involvement of specific sites, history of smoking and alcohol consumption, and family history of psoriasis, were collected from the PsV patients, and correlations between these clinical data and dyslipidemia were analyzed. Measurement data were compared using t test or Mann-Whitney U test, and enumeration data were compared using chi-square test. Results:There were 122 (50.8%) patients with dyslipidemia in the PsV group and 94 (37.6%) in the control group, and the prevalence of dyslipidemia significantly differed between the two groups ( χ2 = 7.48, P = 0.006). The prevalence of hypo-high-density lipoprotein cholesterolemia was significantly higher in the PsV group (29.8%) than in the control group (18.8%; χ2 = 8.15, P = 0.004). The PsV group showed significantly decreased serum levels of total cholesterol (4.5[3.9, 5.2] mmol/L), high-density-lipoprotein cholesterol (1.1[1.0, 1.3] mmol/L), and apolipoprotein A1 (1.2[1.1, 1.4] g/L) compared with the control group (4.9[4.3, 5.4] mmol/L, 1.3[1.1, 1.5] mmol/L, 1.3[1.2, 1.5] g/L, respectively; all P < 0.001). The proportions of males, patients with a history of alcohol consumption, and patients with involvement of the palmoplantar sites were significantly higher in the PsV patients with dyslipidemia (92.6%, 13.1%, 13.8%, respectively) than in those without dyslipidemia (70.7%, 6.0%, 5.0%, respectively; all P < 0.001). Multifactorial logistic regression analysis showed that "male" and "BMI ≥ 25 kg/m 2" were independent risk factors for dyslipidemia in the PsV patients ( OR [95% CI]: 3.94 [1.74, 9.74], 3.18 [1.71, 6.09], respectively), and "involvement of the palmoplantar sites" was independently associated with increased risk of hyperlipidemia ( OR [95% CI]: 3.38 [1.18, 11.01]) . Conclusion:The prevalence of dyslipidemia was higher in PsV patients than in healthy populations, and PsV patients being males, having BMI ≥ 25 kg/m 2 and with involvement of palmoplantar sites may be prone to develop lipid metabolism disorders.

Objective:To retrospectively evaluate the clinical effect of mitral valve repair for rheumatic mitral stenosis.Methods:We retropectively analyze the clinical datd of 50 rheumatic mitral disease patients undergoing mitral valve repair from January 2016 to March 2019, the clinical outcome was compaired with those of patients undergoing mitral valve replacement. The operation time, cardiopulmonary bypass time, blood loss, ICU time, hospital stay, and postoperative cardiac function were analyzed, and followed up for 2 years to assess mitral regurgitation, cardiac function, and complication rates.Results:The time of cardiopulmonary bypass and ascending aorta occlusion in the valve repair group were longer than those in the valve replacement group ( P<0.05), and the postoperative ventilator assistance time, ICU stay time, and hospital stay were shorter than those in the valve replacement group ( P<0.05). After 2 years of follow-up, no patients died in the two groups. The rehospitalization rate in the valve repair group was lower than that in the replacement group ( P<0.05), and there was no significant difference in the reoperation rate between the groups ( P>0.05); There was 1 case (2%) of moderate mitral valve regurgitation in the mitral valve repair group, no moderate or severe mitral valve stenosis, no paravalvular leakage in the mitral valve replacement group, and no significant difference between the two groups ( P>0.05). The left ventricular end-diastolic diameter and left ventricular ejection fraction in the mitral valve repair group were significantly better than those in the mitral valve replacement group ( P<0.05). Conclusion:Mitral valve repair is effective in treating rheumatic mitral stenosis. It is beneficial to protect heart function, reduce postoperative anticoagulation complications, and does not increase the rate of reoperation. It is a safe, effective and feasible treatment.

Objective:To understand the basic characteristics of COVID-19 cases and the virus carrying status of different samples in Ma′anshan.Methods:Descriptive epidemiological method was used to describe the distribution of 2019-nCoV infections in Ma′anshan. Real-time fluorescence RT-PCR was used to detect 2019-nCoV nucleic acid in sputum and/or throat swabs. Data was analyzed by EXCEL and SPSS 20.0. P<0.05 was considered to be statistically significant by using χ2 test. Results:Until 14 March 2020, 38 confirmed cases and no death had been reported in Ma′anshan, there were also 11 asymptomatic infections. 2019-nCoV infection was first detected on January 23, and the last was on February 20. No new infections have been found for 23 consecutive days until March 14; 77.55%(38/49)of the infections were in He county. Among the 1 447 subjects, the positive rate was 4.50% (27/600) in females and 2.60% (22/847) in males (χ 2=3.886, P=0.049). The minimum age of the infections was 4 years and the maximum was 85. There was no significant difference between age groups ( χ2=10.675, P=0.058). Among the 49 infections, 20 of them (40.82%) were from Wuhan, 24 (48.98%) were locally infected, and 5 (10.20%) were imported from other places. For the first positive infections, the positive rate of sputum (100%, 36/36) was higher than the throat swab (77.78%, 28/36), and the difference was statistically significant (χ 2=6.125, P<0.05). Conclusions:In Ma′anshan, 2019-nCoV infections were concentrated in He county, sputum was beneficial to the detection of 2019-nCoV.

Human immune system(HIS)mice are usually used to evaluate the ability of tumor vaccines to induce cytotoxic T lymphocyte(CTL)effects, but they failed to accurately reflect the ability of cancer vaccines to induce humoral immune responses. In this study, human peripheral blood mononuclear cells were isolated by density gradient centrifugation and co-transplanted into NCG mice with in vitro differentiated dendritic cells(DCs)to establish a DC-HIS mouse model. In DC-HIS mice, co-transplanted antigen-presenting cells(HLA-DR+CD11c+)could colonize the spleen of model mice. Moreover, co-transplantation of DCs significantly increased the proportion of activated human CD4+ T/CD8+ T cells and B cells in HIS mice, indicating that DC-HIS mice could better mimic the human immune responses. The immunogenicity of the targeted HER2 protein vaccine(NitraTh-HER2)was evaluated using the DCs-HIS mice. The results showed that the NitraTh-HER2 vaccine was able to induce the production of HER2-specific human IgG antibodies with a significant antibody-dependent cell-mediated cytotoxicity(ADCC)effect and the lysis rate of target cell SK-BR-3 reached 47. 1%. The NitraTh-HER2 vaccine was able to produce antigen-specific CTL effect, and the lysis rate of target cell SK-BR-3 reached 14. 6%. Taken together, the DC-HIS mouse model provides an effective method for predicting the immunogenicity of human tumor vaccines.
10.11665/j.issn.1000-5048.20190615

Objective To explore the effect of single level lumbar disc herniation on the morphology and diameter of sciatic nerve,and to identify the correlation between the diameter change in sciatic nerve and severity of clinical symptoms,as well as the prognosis of surgical treatment in patients with lumbar disc herniation.Methods From January 1,2017 to December 31,2017,Seventy lumbar disc herniation (LDH) patients who underwent single-level posterior lumbar spine surgery were recruited in this retrospective analysis study.Specific data including age,gender,the level of a disc herniation,the type of disc herniation,symptomatic side,surgical procedure were recorded respectively.In addition the morphological changes and the diameter of bilateral sciatic nerve were recorded preoperatively and postoperatively by B-mode ultrasound.Furthermore,the pain in patients and neurological function were evaluated by visual analogue scale (VAS,back pain and leg pain),Japanese orthopaedic association scores-lumbar (JOA) and Oswestry disability index (ODI).The correlation between the diameter of sciatic nerve and clinical features,as well as clinical prognosis of patients were identified in the present study.Results For patients with acute lumbar disc herniation,the diameter of sciatic nerve in affected side was 5.19±1.03 ram,which is significantly higher than that in the unaffected side (4.57±0.64 mm,t=6.735,P=0.000).In addition,preoperative ratio of the affected side to the healthy side of the sciatic nerve showed strong correlation with the VAS of leg pain (r=0.838,P=0.001),JOA (r=-0.857,P=0.001),and ODI score(r=0.881,P=0.000),but not with the VAS of back pain (r=-0.061,P=0.614).Three months after surgery,the diameter of sciatic nerve in the affected side decreased to 4.58±0.63 mm (t=6.865,P=0.000),while the unaffected side showed no significant change(t=0.300,P=0.765).Clinical improvement was observed in all the patients postoperatively.The changes in the diameter of sciatic nerve postoperatively in affected side showed strong correlation to the rate of improvement in VAS of leg (r=0.624,P=0.003),JOA(r=0.615,P=0.003) and ODI scores (r=0.722,P=0.002),but not to the rate of improvement in VAS of back (r=-0.025,P=0.836).Conclusion Single root compression in patients with single level disc herniation might cause morphological changes such as thickening and edema in sciatic nerve,which were closely related to the severity of clinical symptoms and the prognosis of surgical treatment.