BACKGROUND:silencing information regulatory 1(SIRT1)regulates the function of related proteins in chondrocytes in a deacetylated manner and participates in chondrocyte proliferation and differentiation,thereby promoting cartilage defect repair. OBJECTIVE:To screen for signaling pathways with unclear action status after SIRT1 gene knockdown in chondrocytes,as well as diseases or functions that produce changes using high-throughput technology. METHODS:ATDC5 chondrocytes from mice in logarithmic growth phase were divided into two groups:the cells were transfected with SIRT1 gene knockdown negative control lentivirus in control group and SIRT1 gene knockdown lentivirus in experimental group.GeneChip? Mouse Genome 430 2.0 Array was used to detect the mRNA expression at 72 hours after transfection.Applied bioinformatics technology was also used to screen for unclear activation or inhibition signaling pathways and their related factors.Moreover,enrichment of disease or function modules was analyzed. RESULTS AND CONCLUSION:After knocking down the SIRT1 gene,there were 245 signaling pathways with unclear activation or inhibition status in the mouse ATDC5 chondrocytes.According to the ranking of-Log(P-value),we reported the factors in the top 20 signaling pathways with unclear activation or inhibition status,including IGFBP4,TGFBR1,CTGF,COL4A5,LHX2,IL1RL1,and KLF6.According to the ranking of-Log(P-value),there were significant changes in 14 disease or function modules,including cellular growth and proliferation,organism survival,cell death and survival.According to the number of differentially expressed genes,there were significant changes in three disease or function modules,including organismal injury and abnormalities,cancer,and cell death and survival.According to the comprehensive ranking of-Log(P-value)and the number of differentially expressed genes,the disease or function module related to intrinsic immune response was significantly activated.

The ICR(Institute of Cancer Research)mouse infection model was constructed to study the pathogenicity of Sal-monella Telelkebir serotype,and the pathogenic identification of mouse isolates was carried out.Observe the bacterial excretion cycle,evaluate the pathogenicity of Salmonella serotype to mice,and calculate the LD50 by the changes in clinical characteris-tics,histopathology and tissue bacterial load of infected mice;by flight mass spectrometry,biochemical identification,serotype identification,molecular typing and other experiments,compared with human isolates;virulence gene analysis was carried out by PCR experiment and whole genome sequencing.The LD50 of Salmonella Telelkebir is 2.67 × 108 CFU/mL;curling and fluffing may occur 0.5 h after infection;autopsy of dead mice showed that the small intestine was severely congested,with more bubbles and fluid accumulation,cecal necrosis,liver apical degeneration and necrosis,necrotic foci on the surface of the kidney and spleen atrophy;the bacterial load of spleen,kidney,lung,liver and jejunum in mice reached its peak at 3 days after infection,while that of heart at 6 days;the bacterial excretion time of the high-dose group exceeded 100 days;The level of CD3 in tissues increased with increasing dose,with inflammatory cell infiltration,myocardial capillary dilation and hyperemia,large area of vacuoles,degeneration and necrosis of hepatocytes,obvious enlargement of splenic sinus,blurred zoning,thickening of glomerular basement membrane,partial exfoliation of ciliated epithelium,atrophy and exfoliation of jejunal villi;PCR and whole genome sequencing revealed Salmonella-related virulence genes such as cdtB,plt A and pltB.This study was the first to successfully establish the ICR mouse model of Salmonella Telelkebir,demonstrating that this serotype of Salmonella has some pathogenicity.

Objective To observe the clinical efficacy of compound Wufengcao liquid combined with negative pressure wound therapy with instillation(NPWTi)for the treatment of stage Ⅲ-Ⅳ pressure injury(PI),and to preliminarily explore its action mechanism.Methods(1)Clinical research:from January 2019 to October 2022,60 PI patients who were admitted to the Scrofula Department and Wound Care Clinic at Nanjing Municipal Hospital of Traditional Chinese and Western Medicine were randomly divided into normal saline NPWTi group and compound Wufengcao liquid NPWTi group,with 30 cases in each group.Both groups underwent NPWTi under the premise of systemic basic treatment,before treatment,after removing the negative pressure device in the 1st,2nd and 3rd weeks of treatment,the pressure ulcer scale for healing(PUSH)score,the wound bacterial culture detection rate and the wound healing time were counted,and the vascular endothelial growth factor(VEGF)content of wound tissue was detected by ELISA method.(2)Animal experiments:24 SD rats were randomly divided into blank group,model group,normal saline NPWTi group and compound Wufengcao liquid NPWTi group,6 rats in each group.PI rat model was established by local tissue ischemia/reperfusion injury method,and the negative pressure device was removed at the end of each day of treatment.Before treatment and 3,7 and 10 days after treatment,the wound morphology of each group of rats was observed,the wound histopathology was observed by HE staining,the CD34 positive cells rate of wound tissue was detected by immunohistochemistry,and the expressions of p38 mitogen-activated protein kinase(p38 MAPK),nuclear factor-κB p65(NF-κB p65),inducible nitric oxide synthase(iNOS),tumor necrosis factor-α(TNF-α),arginase-1(Arg-1)and transforming growth factor-β(TGF-β)in rat blood and wound tissue were detected by ELISA and RT-qPCR.Results(1)Clinical research:Both groups could effectively reduce the PUSH score and the wound bacterial culture detection rate,shorten the wound healing time,and promote the expression of VEGF in wound tissue,the compound Wufengcao liquid NPWTi group was better than the normal saline NPWTi group(P<0.05).(2)Animal experiments:Compared with blank group,the rats in the model group showed obvious wound inflammatory response and tissue damage,and the CD34 positive cells rate,blood and wound tissue p38 MAPK,NF-κB p65,iNOS and TNF-α levels were significantly increased,Arg-1 and TGF-β level was significantly reduced(P<0.05);Compared with model group,after 7 days of treatment,the normal saline NPWTi group and the compound Wufengcao liquid NPWTi group significantly decreased the wound morphology score,the histopathological morphology was significantly improved,the CD34 positive cells rate was significantly increased(P<0.05),the levels of blood and wound tissue p38 MAPK,NF-κB p65,iNOS,and TNF-α were significantly reduced,and the levels of Arg-1 and TGF-β were significantly increased(P<0.05),and the compound Wufengcao liquid NPWTi group was better than that of the normal saline NPWTi group(P<0.05).Conclusion Compound Wufengcao liquid combined with NPWTi can effectively promote the healing of PI wounds,and its mechanism of action may be by inhibiting the activation and expression of p38 MAPK/NF-κB signaling pathway,thereby regulating the polarization balance of M1/M2 macrophages.

MiR-138-5p is a microRNA that plays an important regulatory role in the pathogenesis of osteoarthritis.MiR-138-5p regulates various biological processes,including inflammation,cell apoptosis and proliferation,and matrix degradation in osteoarthritis,by modulating signaling pathways including nuclear factor-κB,Wnt/β-catenin,and phosphoinositide 3-kinase/AKT.This review summarizes the research progress regarding the mechanism of miR-138-5p in osteoarthritis.

Objective: To analyze the efficacy and safety of the sodium channel blockers (SCB) antiseizure medication in the treatment of focal epilepsy in infants under 6 months of age. Methods: This was a case series study. Infants with focal epilepsy with onset within 6 months of age and treated with SCB attending the Department of Neurology of Beijing Children's Hospital from June 2016 to April 2022 were collected. The clinical data, auxiliary examinations, SCB application, efficacy, adverse reactions, and prognosis were analyzed retrospectively. Patients were grouped according to type of seizure and epileptic syndrome, age of onset and etiology. Chi square test and Fisher exact test were used to analyze the differences between groups statistically. Results: A total of 118 infants were enrolled, 65 males and 53 females, with an age of epilepsy onset of 56 (4, 114) days. Developmental and epileptic encephalopathy was diagnosed in 60 infants, 39 had self-limited neonatal and (or) infantile epilepsy, and 19 had non-syndromic focal epilepsy. Application of SCB: 106 used oxcarbazepine, 2 used lacosamide, 9 switched from oxcarbazepine to lacosamide or a combination of 2 SCB, and 1 used oxcarbazepine, lacosamide, and lamotrigine successively; oxcarbazepine was the first choice in 46 cases. The age at which SCB was applied was 103 (53, 144) days. The children were followed up for 6 months to 6 years. SCB was effective in 89 cases (75.4%), including 70 cases (59.3%) who achieved seizure freedom. The seizure-free rate was higher in the focal epilepsy only group than in the group with other seizure types (64.4% (65/101) vs. 4/17, χ²=9.99, P<0.05). The responder and seizure-free rates were all higher in the group with the onset age of >3-6 months than the group >1-3 months (84.4% (38/45) vs. 62.5% (20/32), 73.3% (33/45) vs. 46.9% (15/32), χ²=4.85 and 5.58, both P<0.05). With the exception of variants in the PRRT2 gene, those with variants in sodium or potassium channels had higher responder and seizure-free rates than those with variants in other genes(86.2% (25/29) vs. 45.5% (10/22), 62.1% (18/29) vs. 22.7% (5/22), χ²=9.65 and 7.82,both P<0.05). The most common adverse event was transient hyponatremia, which happened in 66 cases (55.9%). There were 9 cases of rash, which subsided in 6 cases after discontinuing oxcarbazepine and switching to lacosamide, and 7 cases of electrocardiogram abnormalities, which improved after withdrawing oxcarbazepine and changing to lacosamide in 1 case. Conclusion: SCB are effective and tolerable in the treatment of focal epilepsy in infants under 6 months of age, with better efficacy in patients with genetic variants of the sodium or potassium channel, focal seizures only, and seizure onset >3-6 months of age.
Child ; Female ; Male ; Infant, Newborn ; Humans ; Infant ; Sodium Channel Blockers/adverse effects* ; Oxcarbazepine ; Lacosamide ; Retrospective Studies ; Epilepsies, Partial/drug therapy* ; Seizures ; Sodium ; Anticonvulsants/adverse effects*

Objective To preliminarily verify the effectiveness and safety of bloodletting combined with drug bamboo cups in intervention of degenerative lumbar spinal stenosis,and to explore the prognostic factors that affect the efficacy of TCM regimens in the treatment of DLSS.Methods 64 consecutive patients with degenerative lumbar spinal stenosis were enrolled.Bloodletting combined with drug bamboo cup intervention was used.Acupoints were selected and treated with the same length of the governor channel of the lumbar spine,the first and second side lines of the bladder meridian and Ashi point,weekly 2 times,8 times per course,2 consecutive courses of treatment.Before treatment,after treatment,and 1 month follow-up,the changes of the patient's lumbar spinal stenosis specific scale(SSM),modified Oswestry dysfunction index(ODI),and 12 health survey summary scores(SF-12)were observed.Using SSM symptom or function score≥0.5,the criteria for grouping were first single-factor analysis,and then logistic regression was used to analyze the prognostic factors of the treatment.Results After 2 courses of treatment,the patient's SSM symptom score(2.25±0.56),SSM function score(2.06±0.67),ODI index(15.49±8.72),and SF-12 physiological score(36.31±7.35)were more significant than before treatment Improved,the difference was statistically significant(P<0.05),the SF-12 psychological score(49.70±9.47),the difference was not statistically significant compared with before treatment(P>0.05);the patient's SSM symptom score(2.22±0.54)was followed up for one month,SSM function score(2.09±0.66),ODI index(15.53±8.23),SF-12 physiological score(36.55±7.25),SF-12 psychological score(50.62±9.17),which are significantly better than before treatment,and the difference is statistically significant(P<0.05),the difference was not statistically significant(P>0.05)after 2 courses of treatment.The univariate logistic regression analysis of each influencing factor showed that:BMI,baseline symptom dimension,baseline functional dimension,foraminal stenosis,lateral recess stenosis,and two-stage stenosis had statistically significant differences between the effective and ineffective groups(P<0.05).Conclusion Bloodletting combined with drug bamboo cups has a certain clinical effect on degenerative lumbar spinal stenosis.

Acupuncture and Tuina are the main non-drug therapies for low back pain, which are recommended by the guidelines. Acupuncture and Tuina can alleviate pain, which is regarded as conditional specific outcome, and improve mental, emotional problems, as non-conditional specific outcomes. There are some problems of the outcome assessment of acupuncture and Tuina treatment for pain such as insufficient evaluation of specific effect and unclear evaluation of characteristic outcome. Therefore, the key to above problems is to construct a Specific ouTcomE Assessment Modal of acupuncture and Tuina treatment for pain (STEAM-A&T) based on the qualitive and quantitative methods. By describing the experience, narrative expression, feelings and needs of patients who receiving acupuncture and Tuina treatment, the item banks of acupuncture and Tuina treatment effect are constructed, and the characteristic outcome of acupuncture and Tuina for pain will be screened, and then the relationship model among outcomes is constructed and optimized, which reflected the characteristics of acupuncture and Tuina for pain from multiple dimensions, multiple levels and multiple views. We reveal the relationship between the outcome of acupuncture and Tuina for pain. It will provide a new theory and methods for the construction of specific outcome assessment modal of Traditional Chinese Medicine.

Objective:To compare the effects of different anesthesia methods on perioperative lung injury in pediatric patients with biliary atresia undergoing living donor liver transplantation.Methods:Ninety-one American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ pediatric patients with biliary atresia, regardless of gender, aged 0-36 months, with cardiac function grade of Ⅰ or Ⅱ and Child-Pugh grade of B or C, undergoing elective living donor liver transplantation, were selected. According to the anesthesia method, the pediatric patients were divided into 3 groups: propofol-based anesthesia group (P group, n=30), sevoflurane-based anesthesia group (S group, n=30) and propofol-sevoflurane-based anesthesia group (PS group, n=31). Group P received intravenous infusion of 1% propofol 9-15 mg·kg -1·h -1. In group S, sevoflurane was inhaled and the end-tidal concentration was maintained at 2.6%-4.0%.In PS group, 1% propofol 9-15 mg·kg -1·h -1 was intravenously infused and sevoflurane was inhaled, maintaining an end-tidal concentration at 1.0%-2.5%. Remifentanil 0.1-1.0 μg·kg -1·min -1 was intravenously infused during operation for analgesia, and cisatracurium besylate 1-2 μg·kg -1·min -1 was intravenously infused to maintain muscle relaxation in three groups. Immediately after anesthesia induction (T 0), at 60 min after start of surgery (T 1), at 10 min of anhepatic phase (T 2), at 60 min after portal vein opening (T 3), and immediately after abdominal closure (T 4), the concentrations of serum Clara cell secretory protein 16 (CC16), surfactant protein (SP-D), soluble receptors for advanced glycation end products (s-RAGE), high mobility group protein B1 (HMGB1), tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) were measured using enzyme-linked immunosorbent assay method, and lung compliance (Cdyn) was simultaneously recorded. At T 0-T 4 and 24 h after surgery (T 5), the arterial blood gas analysis was performed to calculate the oxygenation index (OI) and respiratory index (RI). Lung ultrasound scores (LUS scores) were assessed at 24 h before surgery and T 5. The occurrence of pulmonary complications was recorded within 7 days after surgery. The survival was observed for 6 months after surgery. Results:There were no statistically significant differences in serum concentrations of CC16, SP-D and s-RAGE concentrations and LUS scores at different time points between group S and group P ( P>0.05). Compared with S group and P group, the serum CC16 concentrations at T 3 and s-RAGE concentrations at T 3, 4 were significantly decreased, and the C and B scores were decreased at T 5 in PS group ( P<0.05). There were no statistically significant differences in the concentrations of serum HMGB1, IL-1β and TNF-α, Cydn and incidence of ALI/ARDS, pulmonary infection, pleural effusion, and atelectasis within 7 days after surgery among the three groups( P>0.05). The 6-month survival rate was 100% in the three groups. Conclusions:Propofol-sevoflurane-based anesthesia has a better efficacy in reducing perioperative lung injury than propofol-based anesthesia and sevoflurane-based anesthesia in the perioperative period of liver transplantation.

In this study, chronic emotional stress-induced H1N1 influenza susceptibility model was employed to simulate the states of "emotional stagnation" and "liver fire invading lung", and the protective effect of Qinggan Xiefei Fang on viral pneumonia was investigated. Survival rate and morbidity rate of mice were observed within 21 days after H1N1 infection, the symptoms of viral pneumonia and the level of phospholipid peroxidation were detected in lungs of mice after 6-day infection. The experimental results showed that Qinggan Xiefei Fang could alleviate the decline of survival rate and morbidity rate of mice caused by chronic constraint stress loaded with H1N1, inhibit the replication of H1N1 and the production of inflammatory factors, reduce the level of phospholipid peroxidation, and improve the symptoms of pneumonia in mice. The results also showed that compound-target network of Qinggan Xiefei Fang contained 171 compounds and 260 corresponding targets involved in the signaling pathway of oxidative stress, inflammation and immunity. All the above results indicate that Qinggan Xiefei Fang protecting influenza virus pneumonia was related to the regulation of oxidative stress. The animal experimental protocol has been reviewed and approved by Laboratory Animal Ethics Committee of Jinan University, in compliance with the Institutional Animal Care Guidelines.

The discovery of regulatory cell death has led to new breakthroughs in the field of disease treatment. As a novel discovered regulatory cell death in the past decade, ferroptosis is characterized by abnormal increase of intracellular iron ions and peroxidative damage of cell membrane lipids, morphological features of mitochondrial volume reduction, increased mitochondrial membrane density, as well as mitochondria decrease or disappear. The mechanism of ferroptosis is mainly associated with factors such as iron metabolism disorder, lipid metabolism abnormality, amino acid antioxidant system imbalance and oxidative stress. Since the liver is the main organ of human body for storing iron ions, it is necessary to deeply investigate the mechanism of ferroptosis in liver diseases. Relevant studies have shown that ferroptosis plays different roles in various liver diseases and is closely related to the process of liver diseases, including drug-induced liver injury, alcoholic fatty liver disease, non-alcoholic fatty liver diseases, viral hepatitis, liver fibrosis and hepatocellular carcinoma. The aim of this review is to link ferroptosis and liver diseases, concentrating on the iron metabolism disorder, accumulation of lipid peroxides in cell membranes, imbalance of amino acid antioxidant system, hyperpolarization of mitochondrial membrane potential and its accumulation of lipid peroxides, oxidative stress-related transcription factors and other aspects. This review summarizes the regulatory mechanism, current situation and the roles of ferroptosis in liver diseases, in order to provide a new theoretical basis and ideas for the in-depth study of ferroptosis and the treatment of liver diseases.