A novel assisted reduction method in extra-articular fractures of the distal tibia treated with intramedullary nail.

Background: To explore the clinical efficacy and safety of Kirschner wires (KWs) as a blocking screw technique for extra-articular fractures of the distal tibia treated with intramedullary nails (IMNs). Methods: Fifty-three patients were treated with KW-assisted IMN for extra-articular fractures of the distal tibia via the blocking screw technique or Poller screw (PS) technique. The operation time, number of fluoroscopies, number of blocking screws used, blood loss and time to union were compared between the two groups. Additionally, the functional outcomes of the two groups were compared using range of motion (ROM), visual analog scale (VAS), American Orthopedic Foot and Ankle Society (AOFAS), and Lysholm scores. Results: Compared with those in the PS group, the operation time in the KW group was significantly shorter, and the number of fluoroscopy procedures and amount of blood loss during KW surgery were also significantly lower (p = 0.014, 0.001, and 0.036, respectively). Regarding the functional outcomes, there were no significant differences in the ROM, VAS score, AOFAS score or Lysholm score between the two groups (p > 0.05). Conclusion: In the treatment of extra-articular fractures of the distal tibia with nails, the use of KW as a blocking screw technique is safe and reliable.

A paired measles-rubella catch-up campaign in Sichuan China to stop an outbreak and strengthen local immunization programs.

BACKGROUND: China has been working towards measles elimination, but in 2017, measles outbreaks occurred in Ganzi and Aba prefectures of Sichuan province, representing 95% of all provincial cases and jeopardizing measles elimination. METHODS: During March and April 2017, high-performing prefectures were paired with outbreak and other interested counties to jointly conduct a measles-rubella (MR) catch-up campaign, build population immunity, and strengthen the counties' programs. RESULTS: House-to-house search identified 88,383 children in Ganzi that lacked MCV vaccination; 85,144 (96.34%) were vaccinated. Search identified 33,683 children in Aba who were not vaccinated against measles; 33,074 (98.19%) were vaccinated. The supporting prefectures helped install Immunization Information Systems and enroll unvaccinated children into the immunization program.The outbreak ended within a month and incidence has remained low for the subsequent six years. CONCLUSION: A paired catch-up campaign represents an effective model of using measles elimination strategies to strengthen local immunization programs for long-term program effectiveness.

Study on the mechanism of action of Saposhnikovia divaricata and its key phytochemical on rheumatoid arthritis based on network pharmacology and bioinformatics.

ETHNOPHARMACOLOGICAL RELEVANCE: Saposhnikovia divaricata (Turcz.) Schischk (SD; called "fangfeng" in China) has been widely used in the clinical treatment of rheumatoid arthritis (RA) and has shown well therapeutic effects, but the specific mechanisms of action of its bioactive phytochemicals remain unclear. AIM OF THE STUDY: This study aimed to investigate the molecular biological mechanism of SD in treating RA through a pharmacology-based strategy. The SD-specific core ingredient Prangenidin was screened for further in-depth study. MATERIALS AND METHODS: The bioactive phytochemicals of SD and potential targets for the treatment of RA were screened by network pharmacology, and phytochemicals-related parameters such as pharmacology, and toxicology were evaluated. The protein interaction network was established to screen the core targets, and the correlation between the core targets and RA was further validated by bioinformatics strategy. Finally, molecular docking of core components and corresponding targets was performed. The in vitro experiments were performed to elucidate the regulation of Prangenidin on MH7A cells and on the PI3K/AKT pathway, and the in vivo therapeutic effect of Prangenidin was validated in collagen-induced arthritis (CIA) mice. RESULTS: A total of 18 bioactive phytochemicals and 66 potential target genes intersecting with the screened RA disease target genes were identified from SD. Finally, core ingredients such as wogonin, beta-sitosterol, 5-O-Methylvisamminol, and prangenidin and core targets such as PTGS2, RELA, and AKT1 were obtained. The underlying mechanism of SD in treating RA might be achieved by regulating pathways such as PI3K/AKT, IL-17 pathway, apoptosis, and multiple biological processes to exert anti-inflammatory and immunomodulatory effects. Molecular docking confirmed that all core ingredients and key targets had great docking activity. Prangenidin inhibited viability, migration, and invasion, and induced apoptosis in MH7A cells. Prangenidin also reduced the production of IL-1ß, IL-6, IL-8, MMP-1, and MMP-3. Molecular analysis showed that Prangenidin exerts its regulatory effect on MH7A cells by inhibiting PI3K/AKT pathway. Treatment with Prangenidin ameliorated synovial inflammation in the joints of mice with CIA. CONCLUSION: Our findings provide insights into the therapeutic effects of SD on RA, successfully predicting the effective ingredients and potential targets, which could suggest a novel theoretical basis for further exploration of its molecular mechanisms. It also revealed that Prangenidin inhibited viability, migration, invasion, cytokine, and MMPs expression, and induced apoptosis in RA FLSs via the PI3K/AKT pathway.

Biomarkers (mRNAs and non-coding RNAs) for the diagnosis and prognosis of rheumatoid arthritis.

In recent years, diagnostic and therapeutic approaches for rheumatoid arthritis (RA) have continued to improve. However, in the advanced stages of the disease, patients are unable to achieve long-term clinical remission and often suffer from systemic multi-organ damage and severe complications. Patients with RA usually have no overt clinical manifestations in the early stages, and by the time a definitive diagnosis is made, the disease is already at an advanced stage. RA is diagnosed clinically and with laboratory tests, including the blood markers C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) and the autoantibodies rheumatoid factor (RF) and anticitrullinated protein antibodies (ACPA). However, the presence of RF and ACPA autoantibodies is associated with aggravated disease, joint damage, and increased mortality, and these autoantibodies have low specificity and sensitivity. The etiology of RA is unknown, with the pathogenesis involving multiple factors and clinical heterogeneity. The early diagnosis, subtype classification, and prognosis of RA remain challenging, and studies to develop minimally invasive or non-invasive biomarkers in the form of biofluid biopsies are becoming more common. Non-coding RNA (ncRNA) molecules are composed of long non-coding RNAs, small nucleolar RNAs, microRNAs, and circular RNAs, which play an essential role in disease onset and progression and can be used in the early diagnosis and prognosis of RA. In this review of the diagnostic and prognostic approaches to RA disease, we provide an overview of the current knowledge on the subject, focusing on recent advances in mRNA-ncRNA as diagnostic and prognostic biomarkers from the biofluid to the tissue level.

Lateralized brain activities in subcortical vascular mild cognitive impairment with differential Chinese medicine patterns: A resting-state functional magnetic resonance imaging study.

Background: Subcortical vascular mild cognitive impairment (svMCI) is one of the most treatable cognitive impairments, but could be hampered by the high clinical heterogeneities. Further classification by Chinese Medicine (CM) patterns has been proved to stratify its clinical heterogeneities. It remains largely unknown of the spontaneous brain activities regarding deficiency patterns (DPs) and excess patterns (EPs) of svMCI patients based on fMRI data. Objective: We aim to provide neuroimaging evidence of altered resting-state brain activities associated with DPs and EPs in svMCI patients. Methods: Thirty-seven svMCI patients (PAs) and 23 healthy controls (CNs) were consecutively enrolled. All patients were categorized into either the EP group (n = 16) and the DP group (n = 21) based on a quantitative CM scale. The fractional amplitude of low-frequency fluctuation (fALFF) value was used to make comparisons between different subgroups. Results: The DP group showed significant differences of fALFF values in the right middle frontal gyrus and the right cerebellum, while the EP group showed significant differences in the left orbitofrontal gyrus and the left cerebellum, when compared with the CN group. When compared with the EP group, the DP group had markedly increased fALFF values in the left superior temporal gyrus, right middle temporal gyrus and brainstem. The decreased fALFF values was shown in the right anterior cingulate and paracingulate gyri. Among the extensive areas of frontotemporal lobe, the Montreal Cognitive Assessment (MoCA) scores were significantly correlated with the reduced fALFF value of the right middle frontal gyrus and the left orbitofrontal gyrus. Conclusion: Our results indicated that the DPs and EPs presented the lateralization pattern in the bilateral frontal gyrus, which will probably benefit the future investigation of the pathogenesis of svMCI patients.

The Neuroprotective Effects of Danggui-Shaoyao San on Vascular Cognitive Impairment: Involvement of the Role of the Low-Density Lipoprotein Receptor-Related Protein.

Effective drugs for treating dementia are still rare. Danggui-Shaoyao San (DSS), a traditional Chinese medicine, has been widely used in oriental countries for the treatment of various gynecological diseases. Many studies reported that DSS could ameliorate cognitive impairment. In this study, we aimed to investigate the underlying mechanism of DSS on vascular cognitive impairment (VCI) rats. Chronic cerebral hypoperfusion (CCH) is one of the main causes of VCI. CCH resulted in a chain of pathological process, including neuroinflammation, neuronal apoptosis, and oxidative stress. The most widely used animal model of VCI is permanent bilateral common carotid artery occlusion in rats. In this research, we determined whether DSS attenuated cognitive impairment by targeting I kappa B kinase (IKK)/nuclear factor of kappa B (NF-κB) signal pathway in VCI rats. Morris water maze and fear conditioning tests results indicated that DSS [7.2 g/(kg·d)] could improve learning and memory ability in VCI rats. We also found DSS significantly elevated the levels of low-density lipoprotein receptor-related protein 1 (LRP1) in the brain of VCI rats and this might indirectly target the IKK/NF-κB signal pathway to exert inhibitory effect on neuroinflammation, neuronal apoptosis, and oxidative stress in VCI rats. The present researches indicated that DSS might attenuate cognitive impairment by targeting IKK/NF-κB signal pathway in VCI rats and DSS might be a promising agent on VCI.

A Comparative Study on the Effects of Quinic Acid and Shikimic Acid on Cellular Functions of Staphylococcus aureus.

Quinic acid (QA) and shikimic acid (SA), two kinds of natural organic acids, have been reported to exhibit potent antibacterial activity against Staphylococcus aureus. In this study, the effects of QA and SA on the cellular functions of S. aureus were investigated by measuring the intracellular pH, intracellular and extracellular ATP concentrations, succinate dehydrogenase activity, DNA content, and interactions between SA and QA with S. aureus DNA. Studies of the cellular functions demonstrated that QA could significantly decrease the intracellular pH, whereas SA had no effect on intracellular pH. QA and SA reduced succinate dehydrogenase activity and caused a significant decrease in intracellular ATP concentration but no proportional increase in extracellular ATP. Moreover, QA and SA both could remarkably reduce the DNA content of S. aureus and directly interact with genomic DNA. The results suggested that the effects of QA and SA on cellular functions were distinguishable, although the chemical structures of these two compounds were similar. In conclusion, the results of the present research suggested that SA and QA could be used as antibacterial agents in food preservation.

Inhibitory Effect of 2R,3R-Dihydromyricetin on Biofilm Formation by Staphylococcus aureus.

The adherence and biofilm formation of Staphylococcus aureus on food contact surfaces are a major concern for the food industry. Development of antibiofilm agents from polyphenols has drawn much attention due to their potent activity. The present study explored the antibacterial and antibiofilm activities of 2R,3R-dihydromyricetin (DMY) against S. aureus ATCC 29213. It was found that DMY exerted excellent antibacterial and bactericidal properties against S. aureus with minimum inhibitory concentration and minimum bactericidal concentration values of 0.125 and 0.25 mg/mL, respectively. Crystal violet staining and 2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide sodium salt reduction assay demonstrated that DMY significantly reduced the biofilm biomass of S. aureus and decreased the metabolic activity of biofilm cells. Micrographs of light microscope and scanning electron microscope confirmed that DMY inhibited the biofilm formation and caused a disintegration of the complex biofilm architecture. Moreover, DMY was highly efficient in reducing the number of sessile S. aureus cells adhered to stainless steel. These results suggested that DMY could have potential application to control S. aureus contamination in a food processing environment.

Antibacterial effect of 3-p-trans-coumaroyl-2-hydroxyquinic acid, a phenolic compound from needles of Cedrus deodara, on cellular functions of Staphylococcus aureus.

A natural phenolic compound, 3-p-trans-coumaroyl-2-hydroxyquinic acid (CHQA) from needles of Cedrus deodara, has been reported to exhibit strong antibacterial activity. In this study, the molecular structural requirements of CHQA for the antibacterial activity and its effect on the cellular functions of Staphylococcus aureus were investigated. The structure-activity relationship analysis revealed that the p-coumaric acid moiety of CHQA was critical for the antibacterial activity, while the esterification between p-coumaric acid and 2-hydroxyquinic acid was unfavorable. Studies of the cellular metabolism demonstrated that CHQA induced a significant decrease in the intracellular ATP concentration but no proportional increase in the extracellular ATP. It was also found that CHQA slightly increased the respiratory activity and succinate dehydrogenase activity of S. aureus. Meanwhile, CHQA decreased the DNA synthesis of S. aureus and directly interacted with DNA through the groove binding mode.

Establishment of an ex Vivo Model of Nonalcoholic Fatty Liver Disease Using a Tissue-Engineered Liver.

The prevalence of nonalcoholic fatty liver disease (NAFLD), a common cause of chronic liver disease, continues to increase in parallel with that of obesity. Currently, there are no preclinical models to study its complex pathogenesis nor to assess candidate therapies. We have established a tissue-engineered (TE) liver by seeding cells into liver-derived matrix scaffolds and then perfusing the scaffolds with a medium that dynamically provides requisite nutrients, vitamins, minerals, and hormones. Liver-specific biomatrix scaffolds, comprised of almost all of the liver's known extracellular matrix (ECM) components and matrix-bound soluble signals (e.g., growth factors/cytokines), were recellularized with human hepatic cell line HepG2 and perfused with a complete medium enabling the cells to form functioning liver tissue. By perfusing the system with medium with a high fat content, the cells established a TE fatty (TEF) liver model paralleling that of livers in NAFLD patients. The high fat medium containing 500 µM of free fatty acids (FFAs) (oleic acid:palmitic acid = 2:1) caused the TEF livers to accumulate 2-times more fat than those in the control medium over an 8 day culture period and significantly influenced the capacity of fatty acid synthesis and metabolism. PDK4, CYP2E1, and CYP7A1 genes associated with NAFLD and other liver diseases were all up-regulated, and the metabolic activity of CYP3A4 was significantly impaired. Excess FFAs also induced alterations in transporters and key enzymes in the lipid biosynthesis pathway. The TEF liver was used to test if an antisteatotic drug, Metformin, used in patients with NAFLD, would be able to provide effects paralleling those observed in some patients. Metformin treatment of the TEF liver model caused reduced cellular triglycerides, activated AMPK molecule, inhibited mTORC1 signaling pathway, which thus affected the synthesis and metabolism of FFAs. Overall, the TEF liver offers a stable and reproducible model to study the NAFLD development process and antisteatotic drug effects.

Clinical characteristics of patients with chronic obstructive pulmonary disease overlapped with bronchial asthma.

BACKGROUND: The clinical characteristics of patients with chronic obstructive pulmonary disease overlapped with bronchial asthma (COPD-BA) have not been discussed thoroughly. OBJECTIVE: To reveal the clinical features of patients with COPD-BA, to evaluate the risk factors of COPD-BA, and to provide suggestions for COPD individualized therapy. METHODS: A retrospective observational study was performed. A total of 182 patients with COPD (90 with COPD-BA and 92 with pure COPD) were recruited in the study. Information on the following items was collected: demographics, clinical manifestations, complications, laboratory findings, other histories, and inpatient treatments during exacerbation. RESULTS: A total of 182 patients were diagnosed with COPD, with 90 (49.45%) being classified as having COPD-BA. Patients with COPD-BA were more likely to be female (P = .004) and experienced more severe respiratory exacerbations (P = .04) despite being younger (P = .008). Those patients at onset of recurrent cough and sputum production were younger (P = .001). Significantly, a positive asthmatic family history (P = .03) was observed. Patients with COPD-BA usually had higher level of total serum IgE (although no differences were observed), had higher positive rates of the serum specific IgE (P = .004), and were more like to have an allergic history (P = .003). Allergic factor was the risk factor of COPD-BA (odds ratio, 4.477). During hospitalization, patients with COPD-BA tended to be treated with systemic corticosteroids (P = .008). CONCLUSION: Patients with COPD-BA were characterized by persistent airflow limitation with unique clinical features. Allergic factor was associated with the presence of asthmatic characteristics in patients with COPD. When hospitalized for exacerbation, the individualized therapy for COPD-BA might include the use of corticosteroids systemically.

[PROMOTION EFFECT OF CHONDROITIN SULFATE ON PROLIFERATION OF MYOBLASTS].

OBJECTIVE: To research the effect of chondroitin sulfate (CS) on the proliferation of myoblasts and the formation of myotube. METHODS: The myoblasts at passage 5 were used to prepare the cells suspension (1×108 cells/mL), and the experiment was divided into 4 groups based on CS concentration in the medium:group A (0 µg/mL), group B (50 µg/mL), group C (100 µg/mL), and group D (200 µg/mL). The cell morphology and myotube formation were observed by inverted microscope at 4, 5, and 8 days after treatment; MTT was used to detect the cell proliferation at 6 days, and the number of myotube was calculated by HE staining at 8 days. RESULTS: Cells showed spindle shape after adherent, with ovoid nuclei and dense cytoplasm under inverted microscope. When the cell adherent rate was 90%, cells arranged in whorls swirled and showed long fusiform adherent growth; and then nuclei fusion resulted in formation of multincleated myotubes. At 8 days, most myoblasts fused to form myotube in group A, but less myotube was observed in groups B and C, and the least myotube in group D. The absorbance (A) values of groups A, B, C, and D were 0.045 2±0.004 4, 0.540 4±0.096 7, 0.660 9±0.143 4, and 1.069 0±0.039 0 respectively, showing significant difference between other groups (P<0.05) except between groups B and C P>0.05). HE staining observation showed that most myoblasts fused to form myotube in group A, but less myotube in groups B and C, and the least myotube in group D. The number of myotube of groups A, B, C, and D were 222.01±30.02, 193.13±42.46, 170.26±11.96, and 136.88±16.78 respectively, showing no significant difference among groups (F=1.658, P=0.252). CONCLUSIONS: CS can significantly promote the proliferation of myoblast, the promotion is the biggest when CS concentration is 200 µg/mL.