Rabdosichuanin C inhibits productions of pro-inflammatory mediators regulated by NF-κB signaling in LPS-stimulated RAW264.7 cells.

Chronic pharyngitis (CP) is an inflammatory disease of the pharyngeal mucosa and its lymphatic tissues that is difficult to treat clinically. However, research on the exact therapeutic agents and molecular mechanisms of CP is still unclear. In this study, we investigated Rabdosichuanin C (RC) to attenuate lipopolysaccharide (LPS)-induced inflammatory damage in RAW264.7 cells by a combination of targeted virtual screening and in vitro activity assay and further clarified its molecular mechanism of action centering on the IκB/nuclear factor kappa B (NF-κB) pathway. Molecular docking and pharmacophore simulation methods were used to screen compounds with IκB inhibitory effects. Expression of genes and proteins related to the IκB/NF-κB signaling pathway by RC in LPS-induced inflammatory injury model of RAW264.7 cells was detected by PCR, enzyme-linked immunosorbent assay, and Western blot. The docking of RC with IκB protein showed good binding energy, and pharmacophore simulations further confirmed the active effect of RC in inhibiting IκB protein. RC intervention in LPS-induced RAW264.7 cells significantly reduced the expression levels of inflammatory factors tumor necrosis factor-α, interleukins-6, iNOS, and CD-86 at the messenger RNA and protein levels, downregulated IκB, p65 protein phosphorylation levels, and significantly inhibited IκB/NF-κB signaling pathway activation. Virtual screening provided us with an effective method to rapidly identify compounds RC that target inhibit the action of IκB, and the activity results showed that RC inhibits NF-κB signaling pathway activation. It is suggested that RC may play a role in the treatment of CP by inhibiting the IκB/NF-κB signaling pathway.

Protective effects of tanshinone â ¡A on sepsis-induced multiple organ dysfunction: a literature review.

TanshinoneⅡA (TanⅡA) is a noteworthy lipophilic diterpene compound derived from the dried roots of the Traditional Chinese Medicine Danshen () that has various pharmacological properties, including anti-inflammatory, antibacterial, and antioxidative effects. Sepsis is a life-threatening organ dysfunction induced by a dysregulated host response to infection. Recently, increasing attention has been paid to sepsis-induced dysfunction of the intestine, car-diovascular system, lungs, kidneys, liver, and other organs. Experimental studies have shown that TanⅡA has therapeutic potential for sepsis-induced organ dysfunction owing to its anti-inflammatory, anti-apoptotic and regulatory effects on multiple signalling pathways. The purpose of this article is to evaluate the potential multiorgan protective effects of TanⅡA in sepsis.

A preliminary study on the relationship between peripheral blood CD19 +CD27 +B cells, CD4 -CD8 -double-negative T cells, related cytokines and recurrence in patients with neuromyelitis optica spectrum disorders / 中华神经科杂志

Objective:To preliminarily analyze the relationship between peripheral blood CD19 +CD27 +B cells, CD4 -CD8 -double-negative T cells, related cytokines and recurrence in patients with neuromyelitis optica spectrum disorders (NMOSD). Methods:A retrospective analysis was performed on the clinical data of 72 patients with NMOSD admitted to Henan Provincial People′s Hospital between January 2019 and January 2021. According to presence or absence of recurrence within 1 year after treatment, they were divided into non-recurrence group ( n=30) and recurrence group ( n=42). The data such as gender, age and score of Extended Disability Status Scale (EDSS) at admission were collected. The levels of serum triglyceride (TG), total cholesterol (CHO), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A (ApoA) 1 and apolipoprotein B (ApoB) were detected by full-automatic biochemical analyzer. The level of total protein in cerebrospinal fluid was detected by full-automatic programmed protein analyzer. The levels of immunoglobulin (Ig) G and IgM in cerebrospinal fluid were detected by immunoturbidimetry. The counts of peripheral blood CD19 +CD27 +B cells and CD4 -CD8 -double-negative T cells were detected by flow cytometry. The levels of serum interleukin (IL)-6, IL-10 and IL-2 were detected by enzyme-linked immunosorbent assay. Results:EDSS score, neutrophils, proportions of cases with positive aquaporin 4 (AQP4) antibody and autoimmune antibody in the recurrence group were significantly higher than those in the non-recurrence group (all P<0.05). There was no statistically significant difference in serum TG, HDL-C, LDH-C, ApoB, ApoA1, total protein in cerebrospinal fluid, IgG or IgM between the non-recurrence group and the recurrence group (all P>0.05). The proportions of CD19 +B cells, CD19 +CD27 +B cells and CD4 -CD8 -double-negative T cells in the recurrence group were (1.21±0.12)%, (1.61±0.17)% and (1.39±0.25)%, significantly higher than those in the non-recurrence group [(0.85±0.07)%, (1.25±0.12)%, (0.89±0.22)%, t=15.51, 3.89, 12.06, all P<0.05]. The counts of CD19 +B cells, CD19 +CD27 +B cells and CD4 -CD8 -double-negative T cells in the recurrence group were (289.50±17.64) ×10 6/L, (4.67±0.03) ×10 6/L and (64.78±6.53) ×10 6/L, significantly higher than those in the non-recurrence group [(254.56±15.34) ×10 6/L, (3.18±0.03) ×10 6/L, (47.82±4.83) ×10 6/L, t=14.27, 4.26, 12.06, all P<0.05]. The level of serum IL-10 in the recurrence group was lower than that in the non-recurrence group [(18.56±1.97) ng/ml vs (24.72±2.52) ng/ml, t=11.64, P<0.05], while levels of IL-6 and IL-2 were significantly higher than those in the non-recurrence group [(15.12±1.54) pg/ml vs (11.47±1.23) pg/ml, (28.34±2.94) pg/ml vs (22.57±2.36) pg/ml, t=10.75, 8.89, both P<0.05]. Conclusion:The levels of peripheral blood CD19 +CD27 +B cells, CD4 -CD8 -double-negative T cells and related cytokines are abnormal in NMOSD patients, which may be related to the recurrence of NMOSD.

Research progress on the relationship between social isolation and cognitive ability in the elderly / 中华老年医学杂志

Social isolation represents the development of a certain level, either partial or complete, of deprivation of socialization and may have adverse effects in many aspects for the elderly, which can be physiological, psychological and social.Meanwhile, during the course of human life, aging becomes an inevitable process and brings about changes in cognitive ability, which become an important focus of our attention.This paper reviews the research progress on the relationship between social isolation and cognitive ability in the elderly, in order to provide a new perspective for future research on social isolation and cognitive ability in the elderly and also to offer new insight on how to construct a model of intervention and health management for the elderly population with social isolation.

Ilizarov bone transport assisted by a 3D printed patient-specific guide plate for treatment of tibial bone defects / 中华创伤骨科杂志

Objective:To evaluate the efficacy of 3D printed patients-specific guide plates in assisting Ilizarov bone transport in the treatment of tibial bone defects.Methods:A retrospective study was conducted to analyze the clinical data of 24 patients with tibial bone defects who had been admitted to Institute of Trauma Orthopedics, The 80th Army Group Hospital of PLA from January 2018 to March 2022. There were 9 males and 15 females with an age of (49.8±6.5) years, and 4 upper tibial defects, 5 middle tibial defects, and 15 lower tibial defects. According to the methods of repairing bone defects, the patients were divided into 2 groups: a 3D printing group of 10 cases where a 3D printed patient-specific guide plate was used to assist Ilizarov bone transport in the treatment of tibial bone defects, and a traditional group of 14 cases where Ilizarov bone transport was performed in a traditional manner. The 2 groups were compared in terms of operation time, frequency of intraoperative fluoroscopy, axial angulation of the tibia at postoperation and the last follow-up, external fixation time (EFT) and external fixation index (EFI). At the last follow-up, healing of bone defects was evaluated according to the criteria of The Association for the Study and Application of the Method of Ilizarov (ASAMI), functional outcomes were evaluated according to the Paley criteria, and needle infection was recorded according to the Paley classification for complications.Results:There was no statistically significant difference in the preoperative general data between the 2 groups, indicating comparability ( P>0.05). All patients were followed up for (11.3±2.0) months on average after operation. The 3D printing group had significantly shorter operation time [(19.9±2.6) min] and significantly lower frequency of intraoperative fluoroscopy [(3.0±0.8) times] than the traditional group [(38.1±2.2) min and (8.9±1.3) times] (P<0.05), and had significantly better axial angulation of the tibia at postoperation and the last follow-up than the traditional group ( P<0.05). There was no significant difference in EFT or EFI between the 2 groups ( P>0.05), and the last follow-up revealed no significant difference either in bone healing, functional outcomes, or needle infection between the 2 groups ( P>0.05). Conclusion:In the treatment of tibial bone defects, compared with conventional Ilizarov bone transport, the Ilizarov bone transport assisted by a 3D printed patient-specific guide plate demonstrates advantages of shorter operation time, lower intraoperative fluoroscopy, and higher reduction accuracy.

Inhibition and Mechanism of Imatinib on A549 Xenograft Tumor in Nude Mice via PDGF/PDGFR Pathway / 肿瘤防治研究

Objective To investigate the effect of imatinib on the growth of A549 non-small cell lung cancer transplanted tumors and the expression of PDGFB and PDGFRβ proteins in tumor tissues and stroma in nude mice and to explore the underlying tumor suppression mechanism. Methods A transplantation tumor model of A549 non-small cell lung cancer was established in nude mice. The mice were then randomly divided into four groups: control group (0.9%NaCl), low-dose imatinib group (50 mg/(kg·d)), medium-dose imatinib group (100 mg/(kg·d)), and high-dose imatinib group (200 mg/(kg·d)). The effect of different concentrations of imatinib administered by continuous gavage on tumor growth was observed for 28 days. HE staining was performed to observe the pathological changes of tumor tissues. The expression of PDGF/PDGFR pathway-related proteins and the phosphorylation levels of AKT and ERK1/2 proteins in tumor tissues were detected by Western blot analysis. Double immunofluorescence staining was used to detect the expression of PDGFB and PDGFRβ proteins in the tumor stroma. Results Imatinib inhibited the growth of A549 non-small cell lung cancer cells in nude mice, suppressed the expression of PDGFB in tumor tissues, and decreased the phosphorylation levels of PDGFRβ, AKT, and ERK1/2. The expression of PDGFB and PDGFRβ in tumor stromal fibroblasts of the administered group was significantly lower than that of the control group. Conclusion Imatinib exhibits a pronounced inhibitory effect on A549 xenografts of nude mice with non-small cell lung cancer, and its antitumor mechanism may involve the downregulation of PDGFB and PDGFRβ expression in tumor stromal fibroblasts.

Influencing factors of red blood cell transfusion volume for premature neonatal pneumonia and its predictive value for feeding intolerance / 中国输血杂志

【Objective】 To investigate the influencing factors of red blood cell transfusion volume for premature neonatal pneumonia and its predictive value for feeding intolerance. 【Methods】 272 infants of premature neonatal pneumonia treated with red blood cell transfusion were collected as the research objects. Red blood cell transfusion volume was investigated and its influencing factors were analyzed by multiple linear regression. Receiver operating curve (ROC) was used to analyze the predictive value of red blood cell transfusion volume on feeding intolerance in infants with premature neonatal pneumonia. 【Results】 The average red blood cell transfusion volume in infants with premature neonatal pneumonia was (76.19±26.03) mL. Multiple linear regression analysis showed that gestational age, birth weight, volume of blood collection and hemoglobin level before blood transfusion were influencing factors of red blood cell transfusion volume in infants with premature neonatal pneumonia (B=-1.930, -6.215, 1.041, -0.249, P<0.05). The incidence of feeding intolerance in infants with premature neonatal pneumonia was 19.5%. The transfusion volume of feeding intolerance group was significantly higher than that of the non-feeding intolerance group(P<0.05). ROC analysis showed that the area under curve (AUC) of red blood cell transfusion volume for predicting feeding intolerance was 0.755. 【Conclusion】 Gestational age, birth weight, volume of blood collection and hemoglobin level before blood transfusion are influencing factors of red blood cell transfusion volume in infants with premature neonatal pneumonia. The incidence of feeding intolerance in premature neonatal pneumonia is high. The red blood cell infusion volume is of good predictive value for the occurrence of feeding intolerance. Latrogenic blood loss and red blood cell transfusion volume should be minimized clinically.

Clinical characteristics of anticoagulant rodenticide poisoning in northern Anhui analysis of the effect of the vitamin K / 中国临床药理学与治疗学

AIM: To analyze the clinical characteristics of anticoagulant rat poisoning and vitamin K

Comparison between the Mycob.T scanner system and manual microscopy in detecting acid-fast bacilli in sputum specimens / 上海预防医学

ObjectiveTo compare the efficacy between the Mycob.T scanner system and manual microscopy for detecting acid-fast bacilli in sputum specimens. MethodsBetween January and November 2020， a total of 1 519 sputum samples from suspected primary tuberculosis patients from 5 designated tuberculosis hospitals in Shanghai were examined by Smear and BACTEC MGIT 960 liquid culture （liquid culture） methods. Each specimen was subiected to 2 direct smear slides. One slide was stained by Z-N method and examined with manual microscopic method. Another slide was stained and scanned by the Mycob.T system. The efficacy of manual microscopy and the Mycob.T scanner system for detecting acid-fast bacilli in sputum specimens was compared based on the result of liquid culture. Results of the repetitive scanning by the Mycob.T scanner system and the recheck of the manual microscopy were analyzed. ResultsThe average positive rate by the Mycob.T scanner system was 14.4% （219/1 519） while the average positive rate by manual microscopy was 16.3% （248/1 519）. No significant difference was observed （χ2=2.13， P=0.145）. Based on liquid culture confirmation results， the sensitivity of manual microscopy （60.36%） was higher than that of the Mycob.T scanner system （52.94%）， and the difference is statistically significant （χ2=4.38， P=0.036）. Both methods had high specificity （98.94%）. The concordance of the Mycob.T scanner system and manual microscopy was 95.46%， with the kappa value of 0.826. The results of repeatability test of the Mycob.T scanner system and the recheck results of the manual microscopy showed that the coincidence rate of scanning by the Mycob.T scanner system was 99.5% （436/438）， and the recheck coincidence rate by the manual microscopy was 98.6% （432/438）. ConclusionThe Mycob.T scanner system have high specificity for detecting acid-fast bacilli in sputum samples and good consistency with the results of manual microscopy. Compared with manual microscopic examination， the Mycob.T scanner system can greatly alleviate the work intensity.

Isolation of a foodborne Bacillus cereus strain and its effect on intestinal mucosal immunity-associated factors and gut microbial community in mice / 生物工程学报

Bacillus cereus is a common foodborne pathogen. Accidently eating food contaminated by B. cereus will cause vomiting or diarrhea, and even death in severe cases. In the present study, a B. cereus strain was isolated from spoiled rice by streak culture. The pathogenicity and drug resistance of the isolated strain were analyzed by drug sensitivity test and PCR amplification of virulence-associated gene respectively. Cultures of the purified strain were injected intraperitoneally into mice to examine their effects on intestinal immunity-associated factors and gut microbial communities, to provide references for the pathogenic mechanism and medication guidance of these spoilage microorganisms. The results showed that the isolated B. cereus strain was sensitive to norfloxacin, nitrofurantoin, tetracycline, minocycline, ciprofloxacin, spectinomycin, clindamycin, erythrocin, clarithromycin, chloramphenicol, levofloxacin, and vancomycin, but resistant to bactrim, oxacillin and penicillin G. The strain carries seven virulence-associated genes including hblA, hblC, hblD, nheA, nheB, nheC and entFM, which are involved in diarrhea-causing toxins production. After infecting mice, the isolated B. cereus strain was found to cause diarrhea in mice, and the expression levels of immunoglobulins and inflammatory factors in the intestinal mucosae of the challenged mice were significantly up-regulated. Gut microbiome analysis showed that the composition of gut microbial community in mice changed after infection with B. cereus. The abundance of the uncultured_bacterium_f_Muribaculaceae in Bacteroidetes, which is a marker of body health, was significantly decreased. On the other hand, the abundance of uncultured_bacterium_f_Enterobacteriaceae, which is an opportunistic pathogen in Proteobacteria and a marker of dysbacteriosis, was significantly increased and was significantly positively correlated with the concentrations of IgM and IgG. These results showed that the pathogenic B. cereus carrying diarrhea type virulence-associated gene can activate the immune system by altering the composition of gut microbiota upon infection.

Establishment and applicability comparison of four models of acute liver ischemia/reperfusion injury in rat / 中华危重病急救医学

OBJECTIVE@#To clarify the preparation methods of four rat models of liver ischemia/reperfusion injury (IRI) and to determine a liver IRI animal model that is consistent with clinical conditions, has stable pathological and physiological injury, and is easy to operate.@*METHODS@#A total of 160 male Sprague-Dawley (SD) rats were randomly divided into four groups using an interval grouping method: 70% IRI (group A), 100% IRI (group B), 70% IRI with 30% hepatectomy (group C), and 100% IRI with 30% hepatectomy (group D), with 40 rats in each group. Each model was further divided into sham operation group (S group) and ischemia groups of 30, 60, and 90 minutes, with 10 rats in each group. After surgery, the survival status and awakening time of the rats were observed, and the liver lobectomy weight, bleeding volume, and hemostasis time of groups C and D were recorded. Blood samples were collected by cardiac puncture after 6 hours of reperfusion for determination the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), blood urea nitrogen (BUN), serum creatinine (SCr), and γ-glutamyl transpeptidase (γ-GT) in the serum to assess liver and kidney function. Hematoxylin-eosin (HE) staining and immunohistochemical staining of macrophages were performed to analyze the liver tissue structure damage from a pathological perspective.@*RESULTS@#Rats in group A exhibited earlier awakening and acceptable mental status, while rats in the other groups showed delayed awakening and poor mental status. The hemostasis time in group D was approximately 1 second longer than that in group C. The mortality of rats subjected to 60 minutes of 70% hepatic ischemia was 0. Compared to the sham operation group, rats in each experimental group showed significant increases in serum levels of AST, ALT, ALP, BUN, SCr, and γ-GT, indicating impaired liver and kidney function in the rat models of liver IRI. In groups A, B, and C, the 90-minute ischemia subgroup exhibited more pronounced elevation in AST, ALT, ALP, BUN, SCr, and γ-GT levels compared to the 30-minute ischemia subgroup [AST (U/L): group A, 834.94±56.73 vs. 258.74±18.33; group B, 547.63±217.40 vs. 277.67±57.92; group C, 930.38±75.48 vs. 640.51±194.20; ALT (U/L): group A, 346.78±25.47 vs. 156.58±13.25; group B, 408.40±138.25 vs. 196.80±58.60; group C, 596.41±193.32 vs. 173.76±72.43; ALP (U/L): group A, 431.21±34.30 vs. 315.95±15.64; group B, 525.88±62.13 vs. 215.63±17.31; group C, 487.53±112.37 vs. 272.46±92.33; BUN (U/L): group A, 18.35±5.63 vs. 14.32±2.30; group B, 30.21±4.55 vs. 17.41±8.14; group C, 20.50±3.64 vs. 15.93±3.22; SCr (U/L): group A, 27.47±8.91 vs. 22.37±5.66; group B, 43.60±15.57 vs. 36.80±7.95; group C, 63.81±20.24 vs. 42.47±7.03; γ-GT (U/L): group A, 15.64±3.57 vs. 6.82±1.48; group B, 9.28±1.91 vs. 5.62±1.21; group C, 10.98±3.18 vs. 5.67±1.10; all P < 0.05]. The 100% IRI 90-minute group and 100% IRI 90-minute group with 30% hepatectomy exhibited more pronounced increases in the above-mentioned indicators compared to the corresponding 70% IRI control group, indicating increased liver and kidney damage in rats subjected to combined blood flow occlusion and hepatectomy. HE staining showed clear liver tissue structure with intact and orderly arranged cells in the sham operation group, while the experimental groups exhibited cell structure damage, including cell rupture or collapse, cell swelling, nuclear pyknosis, deep cytoplasm staining, cell shedding, and necrosis. The interstitium showed infiltration of inflammatory cells. Immunohistochemical staining revealed a higher number of macrophages in the experimental groups compared to the sham operation group.@*CONCLUSIONS@#Four models of liver IRI in rat were successfully established. As the duration and severity of hepatic ischemia increased, liver cell ischemia worsened, leading to increased hepatocellular necrosis and exhibiting characteristic features of liver IRI. These models can effectively simulate liver IRI following liver trauma, with the group subjected to 100% ischemia and 30% hepatectomy showing the most severe liver injury. The designed models are reasonable, easy to perform, and exhibit good reproducibility. They can be used for investigating the mechanisms, therapeutic efficacy, and diagnostic methods related to clinical liver IRI.

Genetic analysis of a child with Meier-Gorlin syndrome due to a variant of ORC6 gene / 中华医学遗传学杂志

OBJECTIVE@#To analyze the genetic characteristics of a child with Meier-Gorlin syndrome (MGS) due to a homozygous variant of the ORC6 gene.@*METHODS@#A child who was admitted to the Children's Hospital Affiliated to Soochow University on March 25, 2019 due to growth retardation was selected as the study subject. Clinical data of the child was collected. Whole exome sequencing was carried out for the child. Candidate variant was validated by Sanger sequencing and bioinformatic analysis.@*RESULTS@#The child, a 8-year-and-3-month-old male, has featured short stature, small ears, bilateral cryptorchidism and patellar dysplasia. His parents were of first cousins. The child was found to harbor a homozygous c.712A>T (p.K238*) missense variant of the ORC6 gene, which may lead to premature termination of protein translation. Sanger sequencing confirmed that both of his parents were heterozygous carriers. Based on the guidelines from the American College of Medical Genetics and Genomics, the variant was classified as pathogenic (PVS1_Moderate+PM2_Supporting+PM3+PP3+PP4).@*CONCLUSION@#The homozygous c.712A>T (p.K238*) variant probably underlay the MGS in this child.

Delay on detection, and diagnosis of pulmonary tuberculosis and the influencing factors in Inner Mongolia students during 2011-2022 / 中国学校卫生

Objective@#To analyze the delay on detection, care seeking, diagnosis and treatment of tuberculosis among students in Inner Mongolia Autonomous Region (Inner Mongolia) from 2011 to 2022 and its influencing factors, so as to provide support for the prevention and treatment of tuberculosis among students.@*Methods@#The general demographic indicators of students with tuberculosis in Inner Mongolia from January 1, 2011 to December 31, 2022 were collected from the infectious disease monitoring (new) module of the China Disease Prevention and Control Information System. General characteristics and trend of four types of delayed pulmonary tuberculosis patients in students were analyzed. The influencing factors were analyzed using univariate and multivariate Logistic regressions.@*Results@#From 2011 to 2022, there were 6 032 cases of pulmonary tuberculosis among students in Inner Mongolia. The rates of delayed detection, delayed care seeking, delayed diagnosis, and delayed treatment were 51.71%, 64.01%, 7.82 %, and 2.30%, respectively. The results of multivariate Logistic regression analysis showed that tracking ( OR =1.51) in the patient source,league level diagnosis ( OR =3.16) in the diagnostic institution level,and county level diagnosis ( OR =2.41) were positively associated with delayed discovery ( P <0.05). At the level of diagnostic unit, league city level diagnosis ( OR =2.69), and county level diagnosis ( OR =3.67) associated with more delayed care seeking ( P <0.05). Referral ( OR =1.58) and follow up ( OR =2.55), floating population ( OR =2.05), further consultation with a doctor ( OR =2.11), and no results in imaging manifestations ( OR =2.19) were positively associated with delayed diagnosis( P <0.05). The factors contributing to delayed treatment were referral ( OR =1.84), follow up ( OR =4.91), active screening ( OR =5.46), and floating population( OR =1.95)( P <0.05).@*Conclusions@#From 2011 to 2022, the delay on detection and care seeking for tuberculosis patients among students in Inner Mongolia is at a relatively high level, while the delay in diagnosis and treatment is at a relatively low level but shows an increasing trend. It is necessary to focus on the factors associated with delays in identification, diagnosis and treatment in tuberculosis outbreak in the context of school to prevent or reduce school tuberculosis outbreak.

Mechanism of Osteoking in Improving Energy Metabolism in Rats with Myofascial Pain Syndrome Based on cAMP/PKA/PGC1α Signaling Pathway / 中国实验方剂学杂志

ObjectiveFrom the perspective of energy metabolism， the mechanism of Osteoking （OK） in the treatment of myofascial pain syndrome （MPS） was revealed through systems biology prediction combined with holistic animal experimental validation methods. MethodFirstly， the key targets of MPS and their related molecular mechanisms were predicted by the systems biology method， and the core network targets were screened. Then， the network-predicted targets were verified by animal experiments. Specifically， 60 SD rats were randomly divided into normal group， model group， low， medium， and high dose OK groups （0.66， 1.31， 2.63 mL·kg-1）， and positive celecoxib group （21 mg·kg-1）. The MPS model was established by beating combined with a centrifugal exercise method for eight weeks. Except for two days after modeling， the intervention of OK or celecoxib was performed. After the completion of the model， the drug was administered for two weeks. The histopathological changes of trigger point muscle tissue were observed by hematoxylin-eosin staining. The content/activity of Na-K-ATP enzyme （Na+-K+-ATPase）， Ca2+ pump （Ca2+ATPase）， Ca2+， lactate dehydrogenase （LDH）， glutathione （GSH）， malondialal （MDA）， superoxide dismutase （SOD）， cyclic adenosine phosphate （cAMP）， and protein kinase A （PKA） in serum and/or trigger point muscle tissue in MPS rats was detected by enzyme-linked immunosorbent assay. Protein expression levels of PKA and the peroxisome proliferator-activated receptor γ coactivator 1α （PGC1α） in MPS rats were detected by immunohistochemistry. The protein expression levels of PKA， PGC1α， and mitochondrial transcription factor A （TFAM） in MPS rats were detected by Western blot. ResultThe network prediction results suggest that OK acts on the key target of energy metabolism related to the occurrence and development of MPS and may participate in the activation of the cAMP/PKA/PGC1α signaling pathway. The experimental validation results show that compared with the normal group， contracture nodules and disordered arrangement of muscle fibers appear in the trigger point muscle tissue of MPS rats. Na+-K+-ATPase， Ca2+ATPase， SOD activity， Ca2+， and GSH contents in serum and/or trigger point muscle tissue are significantly decreased （P<0.01）. Both LDH activity and MDA contents are significantly increased （P<0.01）， and the protein expression levels of cAMP， PKA， PGC1α， and TFAM are significantly decreased （P<0.01）. Compared with the model group， OK improves the histopathological morphology of trigger point muscle fibers in MPS rats， and after the intervention of OK， Na+-K+-ATPase， Ca2+ATPase， SOD activity， Ca2+， and GSH contents in serum and/or trigger point muscle tissue in MPS rats are significantly increased （P<0.05， P<0.01）. LDH activity and MDA contents are significantly reduced （P<0.05， P<0.01）. The protein expression levels of cAMP， PKA， PGC1α， and TFAM are significantly increased （P<0.05， P<0.01）. ConclusionThe mechanism of OK's intervention in MPS rats may be related to its effective activation of the cAMP/PKA/PGC1α signaling pathway， thus promoting mitochondrial energy metabolism and trigger point muscle fiber damage repair in muscle cells.

Intervention of Osteoking in Rats with Myofascial Pain Syndrome / 中国实验方剂学杂志

ObjectiveTo clarify the intervention effect of Osteoking （OK） in rats with myofascial pain syndrome （MPS） and preliminarily explore the pharmacological mechanism of OK in relieving chronic pain from the perspective of anti-inflammatory disease. MethodThe 60 SD rats were divided into normal group， model group， low， medium， and high dose OK groups （0.66， 1.31， 2.63 mL·kg-1）， and positive celecoxib group （21 mg·kg-1）. The MPS rat model was established by beating combined with the centrifugal exercise method， and the OK and celecoxib were given at the same time. SMALGO paw pressure pain manometer detected the shock pain point tenderness threshold of rats， and the Von-Frey needle and acetone stimulation method detected the mechanical hyperalgesia threshold and cold hyperalgesia stimulation response respectively. Eight weeks and 10 weeks after modeling， the spontaneous discharge state and convulsion response of MPS rats were determined by electromyograph （EMG） instrument. The gait changes of MPS rats were detected using a CatWalk gait analyzer. The expression levels of interleukin-1 β （IL-1β）， tumor necrosis factor-α （TNF-α）， substance P （SP）， and bradykinin （BK） were measured by enzyme-linked immunosorbent assay （ELISA）. The protein expression levels of nuclear transcription factor-κB （NF-κB） inhibiting protein α （IκBα）， phosphorylates （p）- IκBα， NF-κB p65， and p-NF-κB p65 were detected in MPS rats by Western blot. The positive expression of p-NF-κB p65 was detected by immunofluorescence. ResultCompared with the normal group， the model group shows 100% positive rates for EMG signal and local convulsions response at both the 8th and 10th weeks. The tenderness threshold and mechanical hyperalgesia threshold are significantly reduced. Cold hyperalgesia score is significantly increased， and gait is abnormal. The expression levels of serum and trigger points IL-1β， TNF-α， SP， BK， p-IκBα， and p-NF-κB p65， as well as the positive expression intensity of p-NF-κB p65 are significantly increased （P<0.01）. Compared with the model group， the positive rate of EMG detection and local convulsion response is significantly reduced in the medium and high dose OK groups （P<0.05）. The tenderness threshold and mechanical hyperalgesia threshold increase significantly in the medium and high dose OK groups， and the cold hyperalgesia score is significantly reduced in the high dose OK group （P<0.01）. The standing time， swing time， and walking period are significantly increased. The swing speed， maximum contact area， and maximum contact intensity are significantly decreased in the high dose OK group （P<0.05）. Moreover， the protein expression levels of p-IκBα/IκBα and p-NF-κB p65/NF-κB p65 are significantly reduced in the medium and high dose OK groups （P<0.05，P<0.01）. The positive expression intensity of p-NF-κB p65 is significantly decreased in the high dose OK group （P<0.01）. ConclusionThe mechanism of OK in relieving the pain in trigger points of MPS and improving gait abnormalities is related to the downregulation of the NF-κB p65 inflammatory signaling pathway to reduce the expression of inflammatory factors and pain mediators in blood and trigger point tissue.

Safety and immunogenicity of heterologous boost immunization with an adenovirus type-5-vectored and protein-subunit-based COVID-19 vaccine (Convidecia/ZF2001): a randomized, observer-blinded, placebo-controlled trial

BackgroundHeterologous boost vaccination has been proposed as an option to elicit stronger and broader, or longer-lasting immunity. We assessed the safety and immunogenicity of heterologous immunization with a recombinant adenovirus type-5-vectored COVID-19 vaccine (Convidecia) and a protein-subunit-based COVID-19 vaccine (ZF2001). Methods and FindingsWe did a randomized, observer-blinded, placebo-controlled trial in healthy adults previously received one dose of Convidecia. Participants were randomly assigned (2:1) to receive either ZF2001 (vaccine group) or a trivalent inactivated influenza vaccine (TIV) (placebo group) at either 28-day or 56-day intervals. For both regimens, all participants received the 2nd injection with ZF2001 at 4 months after a dose of ZF2001 or TIV, with three-dose schedules of Convidecia/Convidecia/ZF2001 at day 0, day 28 and month 5 (referred to as CV/ZF/ZF (D0-D28-M5)) and CV/ZF/ZF (D0-D56-M6), and two-dose schedules of CV/ZF (D0-M5) and CV/ZF (D0-M6). The primary outcome was the geometric mean titer (GMT) of the neutralizing antibodies against live SARS-CoV-2 virus 14 days after each boost vaccination. The safety outcome was 7-day reactogenicity, measured as solicited local or systemic adverse reactions after each vaccination. Between April 7, 2021, and May 6, 2021, 120 participants were enrolled, among whom 60 were randomly assigned to receive ZF2001 (n=40) or TIV (n=20) at a 28-day interval, and 60 were randomly assigned to receive ZF2001 (n=40) or TIV (n=20) at a 56-day interval. 113 (94.2%) participants received the 2nd injection with ZF2001 4 months after a dose of ZF2001 or TIV. A total of 26 participants (21.7%) reported solicited adverse events within 7 days post boost vaccinations, and all the reported adverse reactions were mild. Among participants receiving ZF001 as second dose, the GMTs of neutralizing antibodies increased to 58.4 IU/ml (42.8-79.8) in 0-28 regimen, and to 80.8 IU/ml (53.1-122.9) in 0-56 regimen at 14 days post first boost dose. The GMTs of neutralizing antibodies increased to 334.9 IU/ml (95% CI 230.4, 486.9) in C/Z/Z (D0-D28-M5) regimen, and 441.2 IU/ml (260.8, 746.4) in C/Z/Z (D0-D56-M6) regimen at 14 days after the third dose. Two-dose schedules of CV/ZF (D0-M5) and CV/ZF (D0-M6) induced comparable antibody level comparable with that elicited by three-dose schedules, with the GMTs of 282.9 IU/ml (142.5, 561.8) and 293.9 IU/ml (137.6, 627.9), respectively. Study limitations include the absence of vaccine effectiveness in real-world, and current lack of immune persistence data and the neutralizing antibodies to Omicron. ConclusionsHeterologous boosting with ZF001 following primary vaccination of Convidecia is safe and more immunogenic than a single dose of Convidecia. These results support flexibility in cooperating viral vectored vaccines and recombinant protein vaccine. Trial RegistrationClinicalTrial.gov NCT04833101

Analysis of related factors of pleural effusion in children with Mycoplasma pneumoniae pneumonia / 中国小儿急救医学

Objective:To explore the related factors of pleural effusion in children with Mycoplasma pneumoniae pneumonia.Methods:The children with Mycoplasma pneumoniae pneumonia hospitalized in the Department of Pediatrics at Hebei General Hospital from October 2016 to February 2020 were divided into pleural effusion group and non-pleural effusion group according to the occurrence of pleural effusion.The general conditions and related examination results of two groups were compared, and the related indexes were further analyzed by multi-factor Logistic regression analysis, and the receiver operating characteristic curve was drawn to evaluate the predictive ability of Logistic regression model.Results:All of 174 children, there were 34 cases in pleural effusion group and 140 cases in non-pleural effusion group.There was no significant difference in sex and age between two groups( P<0.05). Univariate analysis showed significant differences in the presence or absence of mediastinal lymphadenopathy, C-reactive protein, procalcitonin, lactate dehydrogenase, serum ferritin and D-dimer between two groups( P<0.05). Multivariate Logistic regression analysis showed that mediastinal lymphadenopathy, lactate dehydrogenase level(>400 U/L), serum ferritin level(>100 ng/mL) and D-dimer level(>1.65 mg/L) were independent risk factors for pleural effusion in children with Mycoplasma pneumoniae pneumonia( OR=3.850, 4.393, 4.930, 6.790, P<0.05). The area under the receiver operating characteristic curve of Logistic regression model was 0.847, with medium to high diagnostic accuracy( P<0.001). Conclusion:When the children with Mycoplasma pneumoniae pneumonia have mediastinal lymphadenopathy, lactate dehydrogenase level >400 U/L, serum ferritin level >100 μg/L, D-dimer level >1.65 mg/L, we should be highly alert to the occurrence of pleural effusion.

Thoracoumbilical flap combined with random abdominal flap in repair of large-area soft tissue defects of calf in children / 中华显微外科杂志

Objective:To investigate the clinical effect of thoracoumbilical flap combined with random abdominal flap in repair of large-area soft tissue defects of calf in children.Methods:The clinical data of 16 children with large-area soft tissue defects of calf treated with thoracoumbilical flap combined with abdominal random flap from January 2004 to December 2007 in PLA Trauma Orthopaedic Research Institute, 80th Group Military Hospital of the PLA were retrospectively analysed. There were 7 boys and 9 girls aged 8 to 14(11.3 in average) years old. Six cases were crushed by heavy objects, 6 crushed by wheels, 3 by thermal press and 1 by machine strangulation. After thorough debridement, the wound area ranged from 16.0 cm×9.0 cm to 38.0 cm×15.0 cm. Four cases were treated after 3-10 hours of injury by emergency surgery. Twelve cases received surgeries 0-11 days after hospital admission and wound being stabilised. Doppler ultrasound was used to locate the perforating vessels according to the location, size and shape of the wound. Thoracoumbilical flap combined with abdominal random flap were designed and harvested to repair the wound. The sizes of flaps were 18.0 cm×11.0 cm-40.0 cm×16.0 cm. All patients entered follow-up at the outpatient clinic or through WeChat interviews. The appearance, texture of the flap and limb recovery were checked and recorded.Results:After surgery, all of 16 flaps survived, of which 12 flaps had phase-one healing, 3 flaps had small area of necrosis at the edge, which healed after repeated dressing changes and 1 flap developed vascular comproise, and survived after surgical exploration. The donor sites healed in phase-one. All 16 children had 6 months to16 years of follow-up, with an average of 20.7 months. The colour of the flaps was normal with soft texture. The motor function of calf was satisfactory. According to Punor functional evaluation criteria, 12 cases were in excellent and 4 in good.Conclusion:The thoracoumbilical flap combined with abdominal random flap features a reasonable design, strong blood supply and repair of a large area. It is a reliable method for repairing large area soft tissue defects in the calf of children.

Risk score for predicting upper gastrointestinal bleeding after intravenous thrombolysis in elderly patients with acute cerebral infarction / 中华老年医学杂志

Objective:The purpose of this study was to develop a risk score for predicting upper gastrointestinal hemorrhage(UGIH)in acute ischemic stroke(AIS)patients following intravenous thrombolysis.Methods:A retrospective analysis of 203 elderly AIS patients treated with intravenous thrombolysis was conducted in this study.Patients were divided into an UGIH group and a non-NUGIH group, with 40 in the former group and 163 in the latter group.Baseline data at admission were collected to predict UGIH after intravenous thrombolysis.Logistic regression analysis was used to examine independent risk factors affecting UGIH.The score was developed according to regression coefficients.The area under the receiver operating characteristic curve(AUROC)was used to evaluate the sensitivity and specificity of the risk score.The maximum value of the Youden index was used to determine the cutoff value for predicting UGIH.Results:Univariate analysis showed smoking( χ2=4.825, P=0.037), age( χ2=16.927, P<0.001), atrial fibrillation( χ2=14.176, P<0.001), NIHSS score( χ2=29.075, P<0.001), nasogastric intubation( χ2=47.339, P<0.001)and antiplatelet therapy( χ2=56.585, P<0.001)were associated with UGIH.Multivariate analysis found that NIHSS score( OR=2.902, 95% CI: 1.053-8.003)and nasogastric intubation( OR=6.300, 95% CI: 2.281-17.404)were independent risk factors affecting UGIH.The scoring system was named N2, and the total score was 3 points.The N2 scoring system had a good predictive ability(AUROC: 0.828, 95% CI: 0.758-0.899). The cut-off value was 2, the sensitivity was 0.775, and the specificity was 0.791.AIS patients with an N2 score ≥2 were at risk of UGIH after intravenous thrombolysis. Conclusions:The N2 score may be a valid predictive model for AIS patients at high-risk for UGIH after intravenous thrombolysis.Patients with an N2 score≥2 need preventive measures against UGIH.

The effects of deep-learning image reconstruction algorithm on image quality of lower extremity CT angiography with low kV and reverse flow direction scanning / 中华放射学杂志

Objective:To investigate impacts of a deep learning image reconstruction (DLIR) algorithm on image quality of lower extremity CTA with low kVp and reverse flow direction scanning.Methods:From January 2021 to March 2021, fifty patients with suspected lower extremities diseases and received lower extremity CTA with low kVp and reverse flow direction scanning in Union Hospital affiliated to Fujian Medical University were retrospectively collected in this study. Six groups of CT images were reconstructed at the thickness of 0.625 mm using two algorithms including ASIR-V of three blending ratios (ASIR-V 20%, ASIR-V 50% and ASIR-V 80%) and DLIR of three strengths (DLIR-H, DLIR-M and DLIR-L). Regions of interest (ROIs) were placed on proximal abdominal aorta (AA), distal AA, left and right common iliac arteries, left and right femoral arteries (upper segment), left and right superficial femoral arteries (middle segment), left and right popliteal arteries. The CT value and SD value were measured for each group; the signal-noise ratio (SNR) and contrast-noise ratio (CNR) were calculated. The lower extremity CTA was divided into four segments, and the subjective evaluation was independently performed on noise and sharpness using 4 points scales by two radiologists. One-way analysis of variance was utilized to evaluate the differences in subjective scoring and objective parameters among the six groups.Results:For all arteries segments, with the increase of blending ratios for ASIR-V and reconstruction strength of DLIR, the SD values were reduced while SNR and CNR were increased (all P<0.05). Among the six groups, DLIR-H and ASIR-V80% images had lowest SD as well as highest SNR and CNR (all P<0.05). In comparison to ASIR-V20% and ASIR-V50% images, DLIR-H images showed lower SD, higher SNR and CNR values (all P<0.05). There were no statistical differences between ASIR-V80% and DLIR-H images in SD, SNR and CNR values (all P>0.05). Subjective scoring results showed that the DLIR-H images displayed the best noise performance for the entire lower extremity arteries from AA to the foot artery, and the sharpness scores of DLIR-H images were also significantly higher than ASIR-V80% (all P<0.05). Conclusion:DLIR can significantly reduce the image noise and improve the image quality in CTA for abdominal aorta to lower extremity arteries. DLIR-H showed the greatest noise reduction ability and the best effect balancing noise and sharpness, providing highest image quality.