Objective To investigate the effect and mechanism of naringin on acute lung injury(ALI)in septic mice.Methods The acute lung injury mouse model of sepsis was established by intraperitoneal injection of 10 mg·kg-1 lipopolysaccharide.The mice were randomly divided into control group(injected with equal amounts of saline and phosphate buffer),model group(mouse model of sepsis acute lung injury),naringin group(50 mg·kg-1 naringin injected intraperitoneally 1 hour prior to lipopolysaccharide modeling)and BzATP group(50 mg·kg-1 naringin+5 mg·kg-1 BzATP injected intraperitoneally 1 hour prior to lipopolysaccharide modeling).After modeling,lung tissues were taken 24 h later,lung coefficients were calculated;lung tissue interleukin(-ILβ-1 β),interleukin-10(IL-10)and tumor necrosis factor-α(TNF-α)levels were detected by enzyme-linked immunosorbent assay;the expression of purinergic 2X7 receptor(P2X7R),nucleotide-binding oligomerization structural domain-like receptor protein 3(NLRP3)and nuclear factor-κB(NF-κB)proteins were detected by Western blotting.Results The lung coefficients in the control,model,naringin and BzATP groups were(6.26±0.31),(9.09±1.02),(7.02±0.45)and(8.79±0.55)mg·g-1;the contents of TNF-α were(56.41±0.35),(174.68±1.58),(85.23±1.68)and(162.97±3.42)pg·mL-1;the contents of IL-1β were(44.18±7.37),(119.91±17.16),(85.41±2.14)and(104.57±3.39)pg·mL-1;the contents of IL-10 were(50.82±2.89),(28.31±1.86),(42.82±1.98)and(25.19±1.69)pg·mL-1;P2X7 protein expression levels were 0.45±0.16,1.33±0.10,0.64±0.09 and 1.05±0.18;NF-κB protein expression levels were 0.38±0.19,1.29±0.09,0.57±0.11 and 0.92±0.07;NLRP3 protein expression levels were 0.72±0.14,1.28±0.23,0.75±0.09 and 1.27±0.23.Compared with the model group in the control group and naringin group,compared with the naringin group in the BzATP group,the differences of the above indexes were statistically significant(P＜0.01,P＜0.05).Conclusion Naringin attenuates acute lung injury in septic mice by inhibiting the P2X7 receptor-mediated NF-κB/NLRP3 signaling pathway.

Micro vesicles(MVs)are the membrane structures produced by the direct outgrowth of the cell membrane,which can be involved in the pathogenesis of many diseases;MVs can also be used in the diagnosis of diseases and the prediction of prognosis.In recent years,there are more and more researches related to MVs in the field of sepsis,and the mechanism of MVs in sepsis is now reviewed.

AIM:To investigate the effects of cannabinoid receptor agonist WIN55212-2(WIN)on acute lung injury(ALI)in septic mice,and to explore its potential mechanisms through glycolysis.METHODS:A mouse model of septic ALI was established by intraperitoneal injections of lipopolysaccharide(LPS).Male C57BL/6J mice were randomly divided into 4 groups(n=6):(1)control group;(2)LPS group,receiving intraperitoneal injections of LPS at 10 mg/kg;(3)LPS+WIN group,receiving 1 mg/kg WIN intraperitoneally 30 min prior to LPS injection;(4)LPS+WIN+MHY1485[mammalian target of rapamycin(mTOR)activator]group,receiving 10 mg/kg MHY1485 intraperitoneally 1 d before LPS injection and 1 mg/kg WIN plus 10 mg/kg MHY1485 30 min before LPS injection.Tissues were collected 24 h after modeling for analysis.Lung indexes were calculated,and histopathological changes of lung tissues were observed via he-matoxylin-eosin(HE)staining.Inflammatory cytokines interleukin-1β(IL-1β)and IL-10 in lung tissues,and lactic acid and lactate dehydrogenase A(LDHA)in serum were quantified using ELISA.The levels of mTOR/hypoxia-inducible fac-tor-1α(HIF-1α)/6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3(PFKFB3)signaling pathway-related proteins were assessed by Western blot.RESULTS:Compared with control group,the LPS group exhibited an increased lung in-dex,significant lung tissue damage,an increase in IL-1β levels(P＜0.05),a decrease in IL-10 levels(P＜0.05),and el-evated expressions of lactate and LDHA(P＜0.05),along with increased levels of phosphorylated mTOR(p-mTOR),HIF-1α and PFKFB3 proteins(P＜0.05).The LPS+WIN group showed improvements with a reduced lung index(P＜0.05),lessened lung injury,decreased IL-1β levels(P＜0.05),increased IL-10 levels(P＜0.05),and lower levels of lactic acid,LDHA,p-mTOR,HIF-1α,and PFKFB3(P＜0.05).Conversely,the LPS+WIN+MHY1485 group displayed increased lung indexes and lung tissue damage,elevated IL-1β levels(P＜0.05),reduced IL-10 levels(P＜0.05),and higher expressions of lactic acid,LDHA,p-mTOR,HIF-1α and PFKFB3(P＜0.05)compared to the LPS+WIN group.CONCLUSION:WIN55212-2 mitigates sepsis-induced ALI,potentially by modulating the mTOR/HIF-1α/PFKFB3 sig-naling pathway,thereby inhibiting glycolysis and alleviating inflammatory responses.

Objective To investigate the effects of cannabinoid receptor agonist,WIN55212-2(WIN),on acute kidney injury(AKI)in mice with sepsis and its underlying mechanism.Methods Twenty-four healthy male mice were divided into(n=6):Control group,sepsis group(LPS group),sepsis+WIN55212-2 group(LPS+WIN group)and sepsis+WIN55212-2+mTOR activator MHY1485 group(LPS+WIN+MHY group).The sepsis model was constructed by intraperitoneal injection of LPS.After the tissue and blood samples were harvested in 24 h after modeling,ELISA was used to determine the contents of IL-1β,IL-18 and lactate dehydrogenase A(LDHA)in the renal tissues,as well as Scr,kidney injury molecule-1(KIM-1)and lactic acid(LA)in the serum.HE staining was employed to observe the pathological changes of kidney tissue and Paller score was calculated.The expression of p-AKT,p-Mtor and 6-phosphofructokinase-2/fructose-2,6-biphosphatase 3(PFKFB3)in the renal tissues was detected by Western blotting.Results Compared with the Control group,the LPS group had obvious kidney tissue damage,increased Paller score(P＜0.05),increased serum contents of lactic acid,Scr and KIM-1(P＜0.05),up-regulated contents of LDHA,IL-1β and IL-18 in the renal tissues(P＜0.05),and elevated expression levels of p-AKT,p-Mtor and PFKFB3 in the renal tissues(P＜0.05).Milder pathological injury in kidney tissue,decreased Paller score(P＜0.05),reduced contents of lactic acid,Scr and KIM-1(P＜0.05),decreased contents of LDHA,IL-1β and IL-18(P＜0.05),and lower expression of p-AKT,p-Mtor and PFKFB3 were observed in the LPS+WIN group than the LPS group(P＜0.05).The LPS+WIN+MHY group had notably higher Paller score(P＜0.05),raised contents of lactic acid,Scr and KIM-1(P＜0.05),increased contents of LDHA,IL-1β and IL-18(P＜0.05),and up-regulated expression of p-AKT,p-Mtor and PFKFB3(P＜0.05)when compared with the LPS+WIN group.Conclusion WIN can alleviate AKI in sepsis,and it may reduce the level of glycolysis in renal tissue,and alleviate inflammation through inhibiting AKT/Mtor/PFKFB3 signaling pathway.

Chronic refractory wound (CRW) is one of the most challengeable issues in clinic due to complex pathogenesis, long course of disease and poor prognosis. Experts need to conduct systematic summary for the diagnosis and treatment of CRW due to complex pathogenesis and poor prognosis, and standard guidelines for the diagnosis and treatment of CRW should be created. The Guideline forthe diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients ( version 2023) was created by the expert group organized by the Chinese Association of Orthopedic Surgeons, Chinese Orthopedic Association, Chinese Society of Traumatology, and Trauma Orthopedics and Multiple Traumatology Group of Emergency Resuscitation Committee of Chinese Medical Doctor Association after the clinical problems were chosen based on demand-driven principles and principles of evidence-based medicine. The guideline systematically elaborated CRW from aspects of the epidemiology, diagnosis, treatment, postoperative management, complication prevention and comorbidity management, and rehabilitation and health education, and 9 recommendations were finally proposed to provide a reliable clinical reference for the diagnosis and treatment of CRW.

OBJECTIVE: To investigate the mechanism of Tojapride, a Chinese herbal formula extract, on strengthening the barrier function of esophageal epithelium in rats with reflux esophagitis (RE). METHODS: Ten out of 85 SD rats were randomly selected as the sham group (n10), and 75 rats were developed a reflux esophagitis model (RE) by the esophageal and duodenal side-to-side anastomosis. Fifty successful modeling rats were divided into different medicated groups through a random number table including the model, low-, medium-, and high-dose of Tojapride as well as omeprazole groups (n10). Three doses of Tojapride [5.73, 11.46, 22.92 g/(kg•d)] and omeprazole [4.17 mg/(kg•d)] were administrated intragastrically twice daily for 3 weeks. And the rats in the sham and model groups were administered 10 mL/kg distilled water. Gastric fluid was collected and the supernatant was kept to measure for volume, pH value and acidity. Esophageal tissues were isolated to monitor the morphological changes through hematoxylin-eosin (HE) staining, and esophageal epithelial ultrastructure was observed by transmission electron microscopy. The expressions of nuclear factor kappa-light-chain-enhancer of activated B cells p65 (NF-KBp65), κB kinase beta (IKKß), occludin, and zonula occludens-1 (ZO-1) in the esophageal tissues were measured by immunohistochemistry and Western blot, respectively. RESULTS: The gastric pH value in the model group was significantly lower than the sham group (P<0.05). Compared with the model group, gastric pH value in the omeprazole and medium-dose of Tojapride groups were significantly higher (P<0.05). A large area of ulceration was found on the esophageal mucosa from the model rats, while varying degrees of congestion and partially visible erosion was observed in the remaining groups. Remarkable increase in cell gap width and decrease in desmosome count was seen in RE rats and the effect was reversed by Tojapride treatment. Compared with the sham group, the IKKß levels were significantly higher in the model group (P<0.05). However, the IKKß levels were down-regulated after treatment by all doses of Tojapride (P<0.01 or P<0.05). The occluding and ZO-1 levels decreased in the model group compared with the sham group (Ps0.01 or Ps0.05), while both indices were significantly up-regulated in the Tojapride-treated groups (P<0.01 or P<0.05). CONCLUSIONS Tojapride could improve the pathological conditions of esophageal epithelium in RE rats. The underlying mechanisms may involve in down-regulating the IKKß expression and elevating ZO-1 and occludin expression, thereby alleviating the inflammation of the esophagus and strengthening the barrier function of the esophageal epithelium.

Objective:To investigate the present situation of unintended pregnancy within two years postpartum and its influencing factors in China.Methods:Participants who delivered a live birth at 60 hospitals in 15 provinces in the eastern, central and western regions of China during July 2015 to June 2016 were interviewed by using structured questionnaire. Information on occurrence of unintended pregnancy within 2 years after delivery, postpartum contraceptive use, sexual resumption, breastfeeding, and women′s socio-demographic characteristics, and so on, were collected. Life-table analysis, cluster log-rank tests and a 2-level Cox regression model were used for data analysis.Results:A total of 18 045 postpartum women were investigated. The cumulative 1- and 2-year unintended pregnancy rates after delivery were 5.3% (95% CI: 4.5%－6.1%) and 13.1% (95% CI: 11.3%－14.8%), respectively. Cox regression model analysis showed that the risk of unintended pregnancy within 2 years postpartum were increased in younger women, ethnic minorities, women with abortion history, and those who had a vaginal delivery with short lactation time and late postpartum contraceptive initiation (all P<0.01). The risk of postpartum unintended pregnancy was not associated with geographic regions and hospitals where women gave a birth (all P>0.05). Conclusions:In China, the risk of unintended pregnancy within 2 years after delivery is relatively high. Service institutions and service providers should improve the quality of postpartum family planning services, promote the use of high effect contraceptive methods, and educate women to use a method at the time of their sexual resumption or even before.

OBJECTIVE: To explore the screening value of osteoporosis self-assessment tool for Asians (OSTA) and the optimal cut-off value in Chinese healthy physical examination population. METHODS: We selected a healthy physical examination population for bone mineral density screening at the Health Examination Center in Peking University Third Hospital from 2013 to 2016. Quantitative ultrasound (QUS) results were used as the gold standard, and T value ≤-2.5 was defined as osteoporosis patients. Diagnostic test methods were used to analyze the sensitivity, specificity, likelihood ratio and area under curve (AUC) of different cut points of OSTA. The screening accuracy of OSTA at different cut points was compared and the optimal cut-point value determined. RESULTS: A total of 5 833 subjects were included in the study, with an average age of (48.3±17.5) years and 2 594 women (44.5%). The QUS test showed 403 patients with osteoporosis (6.9% of the total population), 343 female osteoporosis patients (13.22% of the female population). In the whole age group, AUC at the international routine cut-off value (OSTA ≤-1) screening for osteoporosis was 0.815 (95%CI: 0.804-0.825), and screening accuracy was higher in the women (AUC=0.837, 95%CI: 0.823-0.851) than that in the men (AUC=0.767, 95%CI: 0.752-0.781; P<0.05). In the whole age group, when the optimal cut-off value was 0, its AUC 0.842 (95%CI: 0.832-0.851) was significantly higher than that when the cut-off value was -1 (P<0.01), and net reclassification improvement (NRI) increased by 5.5%. In the 40 to 65-year-old group, when OSTA cut-off value ≤0, the screening accuracy was significantly higher (NRI=19.5%, P=0.003) than that when it was -1. CONCLUSION The OSTA screening tool had good osteoporosis screening value in healthy people, and the screening accuracy in women is higher than that in men. Increasing the screening cut-off value of OSTA would be helpful to improve the screening accuracy in the whole and 40 to 65-year-old population. There may be different optimal cut-off values for different age group population.
Absorptiometry, Photon ; Adult ; Aged ; Asians ; Bone Density ; Female ; Humans ; Male ; Middle Aged ; Osteoporosis ; Physical Examination ; Risk Assessment ; Self-Assessment ; Sensitivity and Specificity

OBJECTIVETo evaluate chest radiographic findings of children with 2009 influenza (H1N1) virus infection.

METHODData of 235 patients who had microbiologically confirmed H1N1 infection and available chest radiograph obtained between May 1(st) 2009 and Jan. 31(st) 2010 were retrospectively analyzed. The final study group was divided on the basis of clinical course [group 1 mild, outpatients without hospitalization (n = 172); group 2 moderate, inpatients with brief hospitalization (n = 49); group 3 severe, ICU admission (n = 14)]. Four pediatric radiologists reviewed all the chest radiographs of lung parenchyma, airway, pleural abnormalities and also anatomic distribution of the disease.

RESULTNo significant sex or age differences were found among the study groups (P > 0.05). The mean interval between the onset of clinical symptom and the initial chest radiography was (5.91 ± 1.64) days (group 1), (3.60 ± 1.43) days (group 2) and (1.21 ± 0.41) days (group 3), respectively. The differences among the three groups were significant statistically (χ(2) = 13.368, P < 0.01). The ratio of abnormality presented at initial chest X-ray was 79.7% in group 1, 91.8% in group 2 and 100% in group 3. Radiographically, there were prominent peribronchial markings (group 1, 55.2%; group 2, 83.7%; and group 3, 78.6%), consolidation (group 1, 34.3%; group 2, 69.4%; and group 3, 100.0%), hyperinflation (group 1, 22.1%; group 2, 44.9%; and group 3, 50.0%) and ground glass opacity (group 1, 0.6%; group 2, 2.0%; and group 3, 14.3%) in the chest radiographs. The differences of presenting were statistically significant (P < 0.01). In the severe group, the lesions distributed diffusely and asymmetrically with multi-lobe involvements.

CONCLUSIONIn children with 2009 influenza A H1N1 viral infection, the interval between the onset of clinical symptom and initial chest radiography, the ratio of abnormality presented at initial chest X-ray film and the severity of chest film are parallel to their clinical situation.

Child ; Child, Preschool ; Female ; Humans ; Infant ; Infant, Newborn ; Influenza A Virus, H1N1 Subtype ; Influenza, Human ; diagnostic imaging ; virology ; Male ; Retrospective Studies ; Tomography, X-Ray Computed

Objective To study the clinical characteristics and genetic features of SPG4 gene in a family with hereditary spastic paraplegia (HSP). Methods The four patients from one LinYi family were clinically diagnosed as having HSP according to Harding's criteria and their peripheral blood samples were collected. We typed the short tandem repeat (STR) loci closely connected with the known HSP cause gane locus at physical distance and genetic linkage analysis was performed on them. Their haplotypes were structured and then screening of gene mutations was performed. Results Non-elimination of linkage was found between D2S2351 and D2S2255 and cause gene, and the LOD scores in other locus were negative value and eliminated the linkage, which implied that the location was in the ADHSP locus of chromosome 2p22 (SPG4) and the candidate gene was spastin gene. Screening of gene mutations found that the mutation loci lied in heterozygous A and G at nucleotide 1168 in spostin gene. The symptoms of the patients manifested as stiffness, instability or weakness of the legs. Conclusions The patients in this family have typical clinical symptoms of HSP, mainly resulting from the novel mutation (spastin: c1168 A>G).