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Background Painful diabetic peripheral neuropathy (PDPN) has a great impact on an individual’s quality of life. The current researchers’ previous trial suggested that acupuncture was a promising adjunctive treatment for PDPN. However, the underlying mechanism of action of acupuncture treatment for PDPN is still unclear, especially its effects at the cerebral level. The aim of this trial will be to explore how acupuncture works in treating PDPN by using multimodal cerebral imaging. Method and design This will be a randomized controlled trial. A total of 150 participants will be recruited and assigned to one of three groups: the healthy group, the DM without PDPN group and the DM with PDPN group. Participants in the DM without PDPN and the DM with PDPN groups will each be further divided between an electroacupuncture group and a sham electroacupuncture group. Participants will receive six treatment sessions per week for 4 weeks. Multimodal cerebral imaging includes resting-state functional magnetic resonance imaging (rs-fMRI), diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS); this neurophysiological testing will be the primary outcome measure. Subjective pain scales and blood analysis will be a secondary outcome measure and will be used to assess the clinical efficacy of the intervention. Multimodal cerebral imaging will be used to detect cerebral activity changes in each treatment group. The clinical data and fMRI data will be analysed for all the groups. Multiple correlation regression analyses will be used to assess the association between changes in cerebral functional activity and the improvement of clinical outcomes after acupuncture treatment. Discussion This study is based on the results of the researchers’ previous study, and using combined clinical and cerebral function changes, it will help evaluate the effects of acupuncture on PDPN. The investigation of acupuncture’s central mechanism of action will further expand the understanding of acupuncture treatment of PDPN. Trial registration Chinese Clinical Trial Registry ChiCTR1900024109. Registered on 26 June 2019.

Background:. Accumulating evidence suggests that lithium influences mesenchymal stem cell (MSC) proliferation and osteogenic differentiation. As decreased bone formation in femoral heads is induced by glucocorticoids (GCs), we hypothesized that lithium has a protective effect on GC-induced osteonecrosis of femoral heads (ONFH). Methods:. A rat ONFH model was induced by methylprednisolone (MP) and the effect of lithium chloride on the models was evaluated. Micro-computed tomography (CT)-based angiography and bone scanning were performed to analyze the vessels and bone structure in the femoral heads. Hematoxylin and eosin and immunohistochemical staining were performed to evaluate the trabecular structure and osteocalcin (OCN) expression, respectively. Bone marrow-derived MSCs were isolated from the models, and their proliferative and osteogenic ability was evaluated. Western blotting and quantitative real-time polymerase chain reaction were performed to detect osteogenic-related proteins including Runx2, alkaline phosphatase, and Collagen I. Results:. Micro-CT analysis showed a high degree of osteonecrotic changes in the rats that received only MP injection. Treatment with lithium reduced this significantly in rats that received lithium (MP + Li group); while 18/20 of the femoral heads in the MP showed severe osteonecrosis, only 5/20 in the MP + Li showed mild osteonecrotic changes. The MP + Li group also displayed a higher vessel volume than the MP group (0.2193 mm3vs. 0.0811 mm3, P

Background Perivascular epithelioid cell tumor (PEComa) is an uncommon tumor of mesenchymal origin. Cases of PEComa in the liver are extremely rare. Aim To analyze the clinicopathological features and treatment of hepatic PEComa and to evaluate the prognosis after different treatments. Methods Clinical and pathological data of 26 patients with hepatic PEComa were collected. All cases were analyzed by immunohistochemistry and clinical follow-up. Results This study included 17 females and 9 males, with a median age of 50 years. Lesions were located in the left hepatic lobe in 13 cases, in the right lobe in 11, and in the caudate lobe in 2. The median tumor diameter was 6.5 cm. Light microscopy revealed that the tumor cells were mainly composed of epithelioid cells. The cytoplasm contained heterogeneous eosinophilic granules. There were thick-walled blood vessels, around which tumor cells were radially arranged. Immunohistochemical analysis of pigment-derived and myogenic markers in PEComas revealed that 25 cases were HMB45 (+), 23 were Melan-A (+), and 22 SMA (+). TFE3 and Desmin were negative in all cases. All the fluorescence in situ hybridization samples were negative for TFE3 gene break-apart probe. Tumor tissues were collected by extended hepatic lobe resection or simple hepatic tumor resection as the main treatments. Median follow-up was 62.5 mo. None of the patients had metastasis or recurrence, and there were no deaths due to the disease. Conclusion Hepatic PEComa highly expresses melanin and smooth muscle markers, and generally exhibits an inert biological behavior. The prognosis after extended hepatic lobe resection and simple hepatic tumor resection is semblable.

Traditional neurosurgical craniotomy primarily uses two‐dimensional cranial medical images to estimate the location of a patient’s intracranial lesions. Such work relies on the experience and skills of the doctor and may result in accidental injury to important intracranial physiological tissues. To help doctors more intuitively determine patient lesion information and improve the accuracy of surgical route formulation and craniotomy safety, an augmented reality method for displaying neurosurgery craniotomy lesions based on feature contour matching is proposed. This method uses threshold segmentation and region growing algorithms to reconstruct a 3‐D Computed tomography image of the patient’s head. The augmented reality engine is used to adjust the reconstruction model’s relevant parameters to meet the doctor’s requirements and determine the augmented reality matching method for feature contour matching. By using the mobile terminal to align the real skull model, the virtual lesion model is displayed. Using the designed user interface, doctors can view the patient’s personal information and can zoom in, zoom out, and rotate the virtual model. Therefore, the patient’s lesions information can be visualized accurately, which provides a visual basis for preoperative preparation.

BACKGROUND Ear molding is a safe and effective way to treat babies born with ear deformities. In this study, the authors explored the long-term effectiveness of ear molding and determined the factors that relate to recurrence. METHODS A retrospective review of 200 consecutive infants treated with the EarWell System from March of 2018 to August of 2019 was performed. Immediate and long-term effectiveness was evaluated and compared. RESULTS A total of 190 children (314 ears) were included. The mean age at presentation was 16.2 days (range, 0 to 100 days). The most common deformity was constricted ear [172 ears (54.8 percent)], and the rarest deformity was cryptotia [four ears (1.3 percent)]. At the completion of treatment, 10 constricted ears were evaluated to be unsuccessful. The immediate success rates of mild and severe constricted ears were 95.7 percent and 93.1 percent, respectively. The average long-term follow-up was 336 days (range, 180 to 660 days) after completion of treatment. Twenty-two ears (7.2 percent) reverted to their original shape. The long-term success rates of severe constricted ears and prominent ears decreased most significantly, 83.3 percent (p = 0.030) and 66.7 percent (p = 0.042), respectively. Family history led to a decrease of long-term effectiveness of prominent ears. Age at application, sex, duration of molding, and retention taping were not correlated to the long-term outcome. CONCLUSIONS Long-term follow-up demonstrated that in a percentage of babies, the ear deformities did recur after an initially successful treatment. Severe constricted ears and prominent ears are most likely to relapse. CLINICAL QUESTION/LEVEL OF EVIDENCE Therapeutic, IV.

Liying Zhang,1,* Xinhua Chen,2,* Haili Wang,1 Haipeng Huang,1 Mengyuan Li,1 Lin Yao,1 Shiqi Ma,1 Zhen Zhong,1 Hongmei Yang,3 Hongfeng Wang4 1School of Acupuncture and Massage, Changchun University of Chinese Medicine, Changchun, Jilin, 130117, People’s Republic of China; 2Department of Acupuncture and Moxibustion, Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, Jilin, 130021, People’s Republic of China; 3Jilin Ginseng Academy, Changchun University of Chinese Medicine, Jilin, 130117, People’s Republic of China; 4Northeast Asia Institute of Chinese Medicine, Changchun University of Chinese Medicine, Jilin, 130117, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongmei Yang; Hongfeng WangJilin Ginseng Academy, Changchun University of Chinese Medicine, 1035 Boshuo Road, Changchun, Jilin, 130117, People’s Republic of ChinaTel/Fax +86 431 86763992Email yanghm@mit.eduHongfeng WangNortheast Asia Institute of Chinese Medicine, Changchun University of Chinese Medicine, 1035 Boshuo Road, Changchun, Jilin, 130117, People’s Republic of ChinaTel/Fax +86 431 89912521Email ccwhf@126.comIntroduction: Traditional Chinese acupuncture has been demonstrated to be beneficial for treatment of type 2 diabetes mellitus (T2DM). The mechanism of acupuncture on T2DM is crucial for their biological activity as well as their usefulness as tools in biology and medicine. However, its mechanism is poorly understood.Methods: In an effort to explore the mechanism, eight db/db mice (a type of spontaneous T2DM mouse) were treated with adjusting internal organs and dredging channel electroacupuncture (AODCEA) for 2 weeks. Another eight db/db mice were fed as T2DM group (T2DMG), and eight db/m mice were set as normal control group (NCG). Lipopolysaccharide (LPS), interleukin-6 (IL-6), and diabetes-related indicators, such as fasting blood glucose (FBG) and triglyceride (TG), were detected by enzyme-linked immune sorbent assay (ELISA). The V4 region of 16S rRNA gene was analyzed by Illumina sequencing to evaluate the effect of AODCEA on intestinal flora. The amount of short-chain fatty acids (SCFAs) in the feces were determined by gas chromatography-mass spectrometry (GC-MS).Results: Our results indicate that AODCEA treatment can reduce diabetes-related indicators. We observed the increased probiotics such as Blautia and Lactobacillus and decreased opportunist pathogens (Alistipes, Helicobacter, Prevotella) by AODCEA interventions. Importantly, the total amount of SCFAs in the feces of T2DM mice was promoted by AODCEA. Finally, obviously alleviated systemic inflammation was exhibited through AODCEA treatment by detection of lipopolysaccharide (LPS) and interleukin-6 (IL-6) in serum.Conclusion: AODCEA can reshape the structure of intestinal flora, which can increase intestinal SCFAs, affect the circulating LPS level, and reduce the inflammatory response.Keywords: gut microbiota, acupuncture, Type 2 diabetes mellitus, short-chain fatty acids, inflammation, insulin resistance

Summary Since the outbreak of the novel corona virus disease 2019 (COVID-19) at the end of 2019, specific antiviral drugs have been lacking. A Chinese patent medicine Toujiequwen granules has been promoted in the treatment of COVID-19. The present study was designed to reveal the molecular mechanism of Toujiequwen granules against COVID-19. A network pharmacological method was applied to screen the main active ingredients of Toujiequwen granules. Network analysis of 149 active ingredients and 330 drug targets showed the most active ingredient interacting with many drug targets is quercetin. Drug targets most affected by the active ingredients were PTGS2, PTGS1, and DPP4. Drug target disease enrichment analysis showed drug targets were significantly enriched in cardiovascular diseases and digestive tract diseases. An “active ingredient-target-disease” network showed that 57 active ingredients from Toujiequwen granules interacted with 15 key targets of COVID-19. There were 53 ingredients that could act on DPP4, suggesting that DPP4 may become a potential new key target for the treatment of COVID-19. GO analysis results showed that key targets were mainly enriched in the cellular response to lipopolysaccharide, cytokine activity and other functions. KEGG analysis showed they were mainly concentrated in viral protein interaction with cytokine and cytokine receptors and endocrine resistance pathway. The evidence suggests that Toujiequwen granules might play an effective role by improving the symptoms of underlying diseases in patients with COVID-19 and multi-target interventions against multiple signaling pathways related to the pathogenesis of COVID-19.

Aviation medical research shows that disuse osteoporosis will occur after long-term space flight. Even with countermeasures such as exercise and drug treatments, this outcome cannot be avoided in flight. In recent years, the application of artificial gravity devices that change the mechanical microenvironment of bone in microgravity have shown promise in mitigating the risk of disuse osteoporosis. Considering the existence of osteocytes, a fluid-solid coupling finite element model for osteons with two-stage pore structure (Haversian canal, lacunar-canalicular system) was established. In order to study the changes in the mechanical behavior of osteocytes under the action of various artificial gravity (AG) devices, including long-arm centrifuge (LAC), short-arm centrifuge (SAC), and a lower body negative pressure (LBNP) chamber. In addition, the difference in pulsating pressure and static pressure stress caused by the gravity gradient under the AG devices was examined. The simulation results showed that the AG devices could effectively improve the stress level of osteocytes in microgravity. The mechanical microenvironment of osteocytes that was provided by the LAC was closest to that of the Earth's gravitational field. The mechanical stimulation on osteocytes was not significantly improved by the SAC, but from a practical viewpoint, it occupied less space than the LAC. The LBNP chamber created a higher level of stress for osteocytes. Therefore, the LAC was an ideal device for replacing Earth's gravitational field, except for the practical limitations of its physical size. In contrast, the LBNP device had the greatest application potential in training for its expansibility and convenience.

Immune checkpoint inhibition is an important strategy in cancer therapy. Blockade of CTLA-4 and PD-1/PD-L1 is well developed in clinical practice. In the last few years, LAG-3 has received much interest as an emerging novel target in immunotherapy. It was recently reported that FGL1 is a major ligand of LAG-3, which is normally secreted by the liver but is upregulated in several human cancers. FGL1 is a crucial biomarker and target for cancer immunotherapy. As the efficacy of immunotherapy is limited to specific types of patients, the subset of patients needs to be selected appropriately to receive precise treatment according to different biomarkers. To date, there is no test to accurately assess FGL1 expression levels. Nanobodies have some outstanding features, such as high stability, solubility and affinity for diagnostic and therapeutic applications. Here, we report the development and validation of a rapid, sensitive, and cost-effective nanobody-based immunoassay for the detection of FGL1 in human serum. In this study, human FGL1 recombinant protein was expressed and purified for the first time as an immunized antigen. Then, we constructed a nanobody phage display library and screened several nanobodies that bind FGL1 with high affinity. We selected two nanobodies targeting different epitopes of FGL1, one as a capture and the other conjugated with HRP as a probe. The double nanobody-based sandwich ELISA to detect the concentration of FGL1 showed a good response relationship in the range of 15.625–2000 ng/mL, and the recoveries from the spiked sample were in the range of 78% and 100%. This assay could be used as a potential approach for evaluating FGL1 expression for patient stratification and for predicting the therapeutic efficacy of targeting the LAG3/FGL1 axis.

Parkinson disease (PD) is a neurodegenerative disease characterized by selective loss of dopaminergic (DA) neurons in the midbrain. The regulatory role of a variety of microRNAs in PD has been confirmed, and our study is the first to demonstrate that miR-3473b is involved in the regulation of PD. In vitro, an miR-3473b inhibitor can inhibit the secretion of inflammatory factors (TNF-α and IL-1β) in moues microglia cell line (BV2) cells induced by lipopolysaccharide (LPS) and promote autophagy in BV2 cells. In vivo, miR-3473b antagomir can inhibit the activation of substantia nigra pars compacta (SNpc) microglia of C57BL/6 mice induced by 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and promote autophagy. Deletion of TREM2, one of the most highly expressed receptors in microglia, leads to the occurrence and development of PD. ULK1 is a component of the Atg1 complex. Deletion of ULK1 aggravates the pathological reaction of PD. TREM2 and ULK1 are predicted potential targets of miR-3473b by Targetscan. Then, the results of our experiments indicate that transfection with a miR-3473b mimic can inhibit the expression of TREM2 and ULK1. Data from a double luciferase experiment indicate that the 3'-UTR of TREM2, but not ULK1, is the direct target of miR-3473b. Then we aim to investigate the regulation of TREM2 and ULK1 in PD. We found that the expression of p-ULK1 was significantly increased via up-regulation of TREM2. The increased expression of p-ULK1 can promote autophagy and inhibit the expression of inflammatory factors. The regulation of ULK1 by miR-3473b may be accomplished indirectly through TREM2. Thus, miR-3473b may regulate the secretion of proinflammatory mediators by targeting TREM2/ULK1 expression to regulate the role of autophagy in the pathogenesis of inflammation in Parkinson's disease, suggesting that mir-3473b may be a potential therapeutic target to regulate the inflammatory response in PD.

What is known and objective To evaluate the clinical efficacy of acupuncture through a review and analysis of systematic reviews of acupuncture for the treatment of diabetic peripheral neuropathy. Methods Systematic reviews of acupuncture treatment for diabetic peripheral neuropathy were collected by searching CNKI, VIP, Wanfang database, Chinese Biomedical Literature Database (CBM), PubMed, Web of Science and the Cochrane Library. The retrieval period was from the establishment of the database to February 14, 2020. After literature selection and extraction, included reports were evaluated in terms of the quality of the methodology and of the report using criteria from the AMSTAR2 scale and the PRISMA statement. Results and discussion Eighty eight reviews were retrieved. The inclusion criteria were a published systematic evaluation/meta‐analysis/systematic review of acupuncture treatment for diabetic peripheral neuropathy, which included subjects meeting the diagnostic criteria for diabetic peripheral neuropathy, and which compared acupuncture treatment with non‐acupuncture treatment. After the inclusion criteria had been applied, 18 reviews were finally included. According to the PRISMA statement, 3 reports were relatively complete, 12 reports had certain defects, 3 reports had considerable information missing, and 18 reports had extremely low methodological quality according to the AMSTAR2 scale. Current evidence shows that acupuncture improves diabetic peripheral neuropathy and increases nerve conduction velocity. However, the methodological quality of the reviews is generally extremely low, and most of the reviews had certain defects, showing that there is still much room for improvement in terms of the methodology and quality of the research reports. What is new and conclusion Acupuncture appears to have an effect on DPN, effectively improving nerve conduction and clinical symptoms. Although the methodological quality of the included studies was generally very low and defects were frequent, our study highlights areas where improvement in methodology is required. There is a need for further study of the pathogenesis of DPN, and for developing a unified standard for methods of acupuncture treatment, acupoint selection, and adverse reactions reporting. Traditional Chinese medical practices such as acupuncture should adopt an evidence‐based approach to provide greater confidence in their use., This review evaluates and verifies the efficacy of acupuncture in the treatment of diabetic peripheral neuropathy by using the quality of report and methodology, in order to provide reference for clinical decision‐making.

MicroRNA 200a (miR-200a) can inhibit the activation and proliferation of hepatic stellate cells (HSCs) through the transforming growth factor-β (TGF-β) signaling pathway, and improve fibrotic lesions. However, to date, there is no study exploring the role of miR-200a in schistosomiasis liver fibrosis (SLF). In this study, 64 healthy female Balb/c mice were selected and randomly divided into four groups: normal control group (non-infected schistosomiasis group), schistosomiasis model group, Lenti-NC group (lentivirus-negative control group), and Lenti-miR-200a group (lentivirus experimental group). Fluorescence quantitative PCR detection was used to measure the expression level of RNA. HE and Masson staining were used to observe the pathological changes of mouse liver tissue. Furthermore, ELISA was used to detect the serum concentrations of inflammation factors. We found that the expression level of miR-200a in liver tissues gradually decreased with the development of SLF. However, fibrosis factors (α-SMA and TGF-β2) and inflammatory cytokines (IL-4 and IFN-γ) in liver tissues and serum increased and the expression level of Colla I reached its peak in the 6th week of infection. Besides, compared with the schistosomiasis group and Lenti-NC group, the Lenti-NC group had lower levels of α-SMA, TGF-β2 and Colla I (P > 0.05). Furthermore, inflammatory cells and blue collagen fibers appeared and they increased with the development of infection in the schistosomiasis group and Lenti-NC group, but these changes reduced significantly in Lenti-miR-200a group. Our study demonstrated that upregulation of miR-200a might contribute to inhibiting schistosomiasis liver fibrosis., Graphical abstract

Berberine (BBR), a well-known alkaloid, exhibits various pharmacological activities, especially hypolipidemic activity, which has attracted much interest from medicinal chemists in the past decade. However, little progress was made on the structural modification of BBR for improving lipid-lowering activity, mainly due to its unclear biological target and low safety. In this study, a new scaffold of 7,9-disulfatetrahydroberberine was discovered unexpectedly, provided with extremely low cytotoxicity. Hence, a novel series of highly safe 7,9-disulfatetrahydroberberines were designed, synthesized, and evaluated for their hypolipidemic activities. In order to investigate the significance of the 9-position substituent, another new series of 7-sulfatetrahydroberberines were designed and synthesized. Lipid-lowering experiments showed that among these compounds, 5f exhibited the best lipid-lowering activity based on two cell models, 3T3-L1 cells and HepG2 cells. Compared with the blank control, the inhibition rate of compound 5f against total cholesterol was over 60%, the inhibition rate against triglyceride was over 70%, the inhibition rate against low-density lipoprotein cholesterol was approximately 75%, and the inhibition rate against high-density lipoprotein cholesterol was close to 50%, which were far superior to the positive control BBR. This result also verified the feasibility of the development of BBR as a lipid-lowering drug via disubstituted modification at the 7- and 9-position.

Doxorubicin (DOX) acts as the cornerstone in multiple tumour chemotherapy regimens, however, its clinical application is often impeded due to the induction of a severe cardiotoxicity that eventually provokes left ventricular dysfunction and congestive heart failure. Coumestrol (CMT) is a common dietary phytoestrogen with pleiotropic pharmacological effects. The present study aims to investigate the role and mechanism of CMT on DOX-induced cardiotoxicity. Mice were intragastrically administrated with CMT (5 mg/kg/day) for consecutive 2 weeks and then received a single intraperitoneal injection of DOX (15 mg/kg) to mimic the clinical toxic effects after 8-day additional feeding. To verify the role of 5' AMP-activated protein kinase alpha (AMPKα), AMPKα2 global knockout mice were used. H9C2 cells were cultured to further validate the beneficial role of CMT

OBJECTIVES: Conservative treatments are usually the preferred choices for newly diagnosed adult otitis media with effusion (OME). This study was performed to explore the efficacy of conservative treatments, including medication and eustachian tube auto-inflation (ETA), for treating OME in adults and to analyze its predictors. MATERIALS AND METHODS: A total of 107 adult patients with OME were included. All patients completed two weeks of conservative treatments including medication alone or the combination of medication and ETA. RESULTS: The numbers of patients with only one and both ears affected were 79 and 28, respectively, and therefore, 135 affected ears were included. After treatment, 75 affected ears were classified as responders (55.6%), while 60 ears were classified as nonresponders (44.4%). Four predictive factors, including age, air-bone gap (ABG), tubomanometry value (TMM), and the treatment plan (all p50 years), ABG

Parkinson’s disease (PD) is a neurodegenerative disease characterized by bradykinesia, rigidity, and tremor. Age is the main risk factor. Long noncoding RNAs (lncRNAs) are novel RNA molecules of more than 200 nucleotides in length. They may be involved in the regulation of many pathological processes of PD. PD has a variety of pathophysiological mechanisms, including alpha-synuclein aggregate, mitochondrial dysfunction, oxidative stress, calcium homeostasis, axonal transport, and neuroinflammation. Among these, the impacts of lncRNAs on the pathogenesis and progression of PD need to be highlighted. lncRNAs may serve as putative biomarkers and therapeutic targets for the early diagnosis of PD. This study aimed to investigate the role of lncRNAs in various pathological processes of PD and the specific lncRNAs that might be used as putative diagnostic biomarkers and therapeutic targets of PD.

The development of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is an ongoing and challenging research field. However, the dynamic motion of the binding site of EGFR has not been accurately depicted, hindering the improvement of EGFR TKI. For this reason, about 33 protein complexes (32 EGFR proteins plus 1 ErbB4 protein) were carefully curated and subsequently studied for dynamic movements of their binding sites by molecular dynamics simulations in this study. The analysis of root mean square deviation (RMSD) revealed that T790M mutation can make an impact on dynamic motion of binding sites; the RMSD value of the EGFR binding site was unrelated to inhibitory activity. The analysis of the radius of gyration (Rg) revealed that T790M can slightly shrink the value of Rg, thereby influencing the shape of the EGFR binding site. More interestingly, the Rg value can exhibit weak correlation with inhibitory activity of most inhibitors. The relationship between Rg and biological activity deserve our serious interest since the best scoring function, Xscore, cannot distinguish highly active EGFR inhibitors. The root mean square fluctuation (RMSF) analysis of key residues derived from binding sites indicated that the most flexible residue was ASP800 with a large RMSF value against the steady residue ALA743 with a small RMSF value, and two other residues (MET793 and LEU844) were supposed to be involved with molecular recognition. In short, the obtained results would be more effective for guiding the development of a novel EGFR kinase inhibitor.

Objective To study the antipyretic and anti-inflammatory constituents from the active fraction of Reduning (RDN) Injection. Methods In this study, the active fraction of RDN Injection was screened by the LPS-induced mouse endotoxin shock model. The chemical constituents were isolated by chromatography on HP-20 macroporous adsorptive resins, silica gel, ODS columns and reverse phase MPLC and HPLC repeatedly, and their structures were elucidated based on spectroscopic analysis (HR-ESI-MS, NMR, ECD) and chemical methods. Meanwhile, we evaluated the anti-inflammatory activities of the isolates by measuring their inhibitory effects on TNF-α production in LPS stimulated RAW 264.7 macrophages. Results The 95% ethanol eluate of RDN Injection by the macroporous adsorption resin column was proved to be the antipyretic and anti-inflammatory active fraction of this injection. A novel iridoid, named jasminoide A (1), and a new guaiane sesquiterpenoid, named (1R,7R,8S,10R)-7,8,11-trihydroxy-4-guaien-3-one (2), were isolated from Reduning injection, and compound 2 can inhibit TNF-α production with IC50 values of 72.24 µmol/L. Conclusion In this study, two new terpenoids were isolated from Reduning Injection, and compound 2 showed inhibitory activity against LPS-activated TNF-α production in RAW 264.7 cells in vitro.

Background Diabetic cognitive impairment (DCI) is a serious chronic complication caused by diabetes. The pathogenesis of DCI is complex, but brain nerve injury and brain nerve cell apoptosis are important pathological changes. Multimodal brain imaging is one of the most important techniques to study the neural mechanism of the brain. For the clinical treatment of DCI, there is no effective targeted Western medicine and a lack of clear drug intervention methods. Therefore, there is an urgent need to find effective complementary and alternative methods and clarify their mechanism. This research seeks to explore the multimodal brain imaging effect of “Adjust Zang-fu and Arouse Spirit” electroacupuncture for DCI. Methods This clinical research will be a randomized, sham-controlled pilot trial. Eligible participants will be randomly assigned to the intervention group (n = 60) and the control group (n = 30). The intervention group will be divided into the “Adjust Zang-fu and Arouse Spirit” electroacupuncture group (n = 30) and sham electroacupuncture group (n = 30). All participants will continue to receive routine hypoglycemic therapy. The treatment period is the same in both groups. The primary outcomes include functional magnetic resonance imaging (fMRI), magnetic resonance spectroscopy (MRS), Montreal Cognitive Assessment Scale (MoCA), and Clinical Dementia Rating (CDR). The secondary outcomes include blood glucose and blood lipid tests, Instrumental Activities of Daily Living Scale (IADL), Hachinski Ischemic Scale (HIS), Self-Rating Anxiety Scale (SAS), and Self-Rating Depression Scale (SDS). Outcomes will be assessed at baseline and before and after treatment, and adverse events will be examined. Inter- and intragroup analyses will be performed. Discussion This randomized controlled study, combined with multimodal brain imaging techniques and a clinical evaluation scale, was designed to explore the mechanism of “Adjust Zang-fu and Arouse Spirit” electroacupuncture in improving the central nervous system in DCI. Trial registration Chinese Clinical Trial Registration ChiCTR2000040268. Registered on 26 November 2020

Circular RNAs (circRNAs) have been implicated in the dysfunction of vascular smooth muscle cells (VSMCs), which is linked with the development of abdominal aortic aneurysm (AAA). Herein, we explored the precise action of circRNA fibronectin type III domain containing 3B (circ-FNDC3B) in VSMC injury triggered by angiotensin II (Ang-II).Circ-FNDC3B, microRNA (miR) -143-3p, and a disintegrin and metalloproteinase 10 (ADAM10) were quantified by quantitative real-time polymerase chain reaction or western blot assay. Ribonuclease R and subcellular localization assays were applied to characterize circ-FNDC3B. Cell viability, apoptosis, and proliferation were assessed by the Cell Counting Kit-8 assay, flow cytometry, and 5-Ethynyl-2' -Deoxyuridine assay, respectively. The levels of tumor necrosis factor alpha, interleukin-6, superoxide dismutase, and malonaldehyde were estimated by enzyme-linked immunosorbent assay. Direct relationship miR-143-3p and circ-FNDC3B or ADAM10 was verified by dual-luciferase reporter and RNA immunoprecipitation assays.Circ-FNDC3B was highly expressed in AAA tissues and Ang-II-treated VSMCs. Knocking down circ-FNDC3B alleviated Ang-II-induced VSMC injury. Mechanistically, circ-FNDC3B directly targeted miR-143-3p, and miR-143-3p was a downstream mediator of circ-FNDC3B in regulating cell injury induced by Ang-II. ADAM10 was directly targeted and inhibited by miR-143-3p. MiR-143-3p-mediated inhibition of ADAM10 relieved Ang-II-induced VSMC injury. Furthermore, circ-FNDC3B acted as a competing endogenous RNA for miR-143-3p to modulate ADAM10 expression.Our findings suggested that circ-FNDC3B silencing ameliorated cytotoxicity triggered by Ang-II in VSMCs at least partially depending on the regulation of the miR-143-3p/ADAM10 axis.

Objective This study aimed to probe the function of microRNA-181b-5p (miR-181b-5p)/protein inhibitor of activated STAT1 (PIAS1)/protein arginine methyltransferase 1 (PRMT1) axis in the progression of alcoholic fatty liver disease (AFLD). Methods A rat model of AFLD was established and treated with altered miR-181b-5p, PIAS1 or PRMT1 expression constructs to identify their effects on liver function, serum inflammation, liver tissue oxidative stress, hepatocyte apoptosis and pathological changes of liver tissue in rats using a series of assays. miR-181b-5p, PIAS1 and PRMT1 levels were detected, and the targeting relationship between miR-181b-5p and PIAS1 was confirmed. Results MiR-181b-5p and PRMT1 were elevated while PIAS1 was reduced in AFLD rat liver tissues, miR-181b-5p inhibition, PIAS1 overexpression or PRMT1 inhibition improved liver function, attenuated inflammation, oxidative stress, pathological changes and hepatocyte apoptosis in AFLD rat liver tissues. The impacts of miR-181b-5p inhibition on AFLD rats were reversed by PIAS1 silencing. PIAS1 was confirmed as a target gene of miR-181b-5p, and miR-181b-5p regulated PRMT1 expression through binding to PIAS1. Conclusion Inhibiting miR-181b-5p can promote the expression of PIAS1, thereby inhibiting PRMT1 and ultimately improving AFLD.

The objectives of the present study were to determine whether simvastatin (SIM) could reverse the harmful effects on titanium rod osseointegration in ovariectomized rats fed high-fat diet (HFD). Ovariectomized female Sprague–Dawley rats were randomly allocated to three groups and received SIM treatment plus HFD for 12 weeks. We then evaluated the microstructure parameters, histological parameters, biomechanical parameters, bone turnover, and blood lipid level. After 12 weeks of treatment, SIM can significantly improve bone formation around the titanium rod and osseointegration including higher values of maximum push-out force, bone area ratio (BAR), bone-to-implant contact (BIC), bone mineral density (BMD), bone volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), mean connective density (Conn.D) when compared with the HFD group. In addition, system administration of SIM showed positive effects on collagen type 1 cross-linked C-telopeptide (CTX-1), procollagen I N-terminal propeptide (PINP), total cholesterol (TC), triglycerides (TGL), low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol. Compared with the HFD group, lower values of CTX-1, P1NP, TC, TGL and LDL were observed in the SIM+HFD group (P

BACKGROUND Colorectal cancer (CRC) is considered to be a worldwide health problem because of its increasing incidence and prevalence. Surgery offers an opportunity for cure, but the postoperative recurrence rate is still high despite the advancement of chemotherapy. This study aimed to assess the efficacy and safety of prolonged capecitabine chemotherapy following CAPOX chemotherapy for stage III CRC after radical surgery. MATERIAL AND METHODS This study included 212 patients with stage III CRC undergoing open radical surgery from July 2010 to June 2015. Among those patients, 104 patients received prolonged capecitabine chemotherapy (prolonged group) following 8 cycles of CAPOX regimen chemotherapy, while the other 108 patients (control group) received no prolonged chemotherapy. The prolonged chemotherapy consisted of capecitabine (1000 mg/m² per day for 2 weeks) and was repeated every 3 weeks for 8 cycles at most. Long-term survival and toxicities were retrospectively compared. RESULTS Patient characteristics did not differ between the 2 groups. For all patients, no significant difference was found in the 3-year disease-free survival (DFS) (P=0.7775) or 3-year overall survival (OS) rates between the 2 groups (P=0.5787). The prolonged group had significantly higher frequency of hand-foot syndrome (P=0.0267) and paresthesia (P=0.0164). In further subgroup analyses, no benefit for 3-year DFS or 3-year OS of prolonged capecitabine chemotherapy was found in colon cancer or rectal cancer. CONCLUSIONS Prolonged capecitabine chemotherapy following CAPOX regimen chemotherapy failed to improve the survival of patients with stage III CRC after radical surgery.

Mechanical allodynia is a cardinal feature of pathological pain. Recent work has demonstrated the necessity of Aβ-low-threshold mechanoreceptors (Aβ-LTMRs) for mechanical allodynia-like behaviors in mice, but it remains unclear whether these neurons are sufficient to produce pain under pathological conditions. We generated a transgenic mouse in which channelrhodopsin-2 (ChR2) is conditionally expressed in vesicular glutamate transporter 1 (Vglut1) sensory neurons (Vglut1-ChR2), which is a heterogeneous population of large-sized sensory neurons with features consistent with Aβ-LTMRs. In naive male Vglut1-ChR2 mice, transdermal hindpaw photostimulation evoked withdrawal behaviors in an intensity- and frequency-dependent manner, which were abolished by local anesthetic and selective A-fiber blockade. Surprisingly, male Vglut1-ChR2 mice did not show significant differences in light-evoked behaviors or real-time aversion after nerve injury despite marked hypersensitivity to punctate mechanical stimuli. We conclude that optogenetic activation of cutaneous Vglut1-ChR2 neurons alone is not sufficient to produce pain-like behaviors in neuropathic mice. SIGNIFICANCE STATEMENT Mechanical allodynia, in which innocuous touch is perceived as pain, is a common feature of pathological pain. To test the contribution of low-threshold mechanoreceptors (LTMRs) to nerve-injury-induced mechanical allodynia, we generated and characterized a new transgenic mouse (Vglut1-ChR2) to optogenetically activate cutaneous vesicular glutamate transporter 1 (Vglut1)-positive LTMRs. Using this mouse, we found that light-evoked behaviors were unchanged by nerve injury, which suggests that activation of Vglut1-positive LTMRs alone is not sufficient to produce pain. The Vglut1-ChR2 mouse will be broadly useful for the study of touch, pain, and itch.

Neuropathic pain is a major health problem that affects up to 7–10% of the population worldwide. Currently, neuropathic pain is difficult to treat because of its elusive mechanisms. Here we report that orphan G protein-coupled receptor 151 (GPR151) in nociceptive sensory neurons controls neuropathic pain induced by nerve injury. GPR151 was mainly expressed in non-peptidergic C-fibre dorsal root ganglion neurons and highly upregulated after nerve injury. Importantly, conditional knockout of Gpr151 in adult nociceptive sensory neurons significantly alleviated chronic constriction injury-induced neuropathic pain-like behaviour but did not affect basal nociception. Moreover, GPR151 in DRG neurons was required for chronic constriction injury-induced neuronal hyperexcitability and upregulation of colony-stimulating factor 1 (CSF1), which is necessary for microglial activation in the spinal cord after nerve injury. Mechanistically, GPR151 coupled with P2X3 ion channels and promoted their functional activities in neuropathic pain-like hypersensitivity. Knockout of Gpr151 suppressed P2X3-mediated calcium elevation and spontaneous pain behaviour in chronic constriction injury mice. Conversely, overexpression of Gpr151 significantly enhanced P2X3-mediated calcium elevation and dorsal root ganglion neuronal excitability. Furthermore, knockdown of P2X3 in dorsal root ganglia reversed chronic constriction injury-induced CSF1 upregulation, spinal microglial activation and neuropathic pain-like behaviour. Finally, the coexpression of GPR151 and P2X3 was confirmed in small-diameter human dorsal root ganglion neurons, indicating the clinical relevance of our findings. Together, our results indicate that GPR151 in nociceptive dorsal root ganglion neurons plays a key role in the pathogenesis of neuropathic pain and could be a potential target for treating neuropathic pain.

Cardiac ischemia impairs angiogenesis in response to hypoxia, resulting in ventricular remodeling. Garcinoic acid (GA), the extraction from the plant garcinia kola, is validated to attenuate inflammatory response. However, the role of GA in heart failure (HF) and neovascularization after myocardial infarction (MI) is incompletely understood. The present study is striving to explore the role of GA and the potential mechanism of which in cardiac function after MI. SD rats were randomized into sham group, MI+vehicle group, and MI+GA group in vivo. Human umbilical endothelial cells (HUVECs) were cultured in vehicle or GA, and then additionally exposed to 2% hypoxia environment in vitro. MI rats displayed a dramatically reduced myocardial injury, cardiac function and vessel density in the peri-infarcted areas. GA delivery markedly improved cardiac performance and promoted angiogenesis. In addition, GA significantly enhanced tube formation in HUVECs under hypoxia condition. Furthermore, the expressions of pro-angiogenic factors HIF-1α, VEGF-A and bFGF, and pro-angiogenic proteins phospho-VEGFR2Tyr1175 and VEGFR2, as well as phosphorylation levels of Akt and eNOS were increased by GA treatment. In conclusion, GA preserved cardiac function after MI probably via promoting neovascularization. And the potential mechanism may be partially through upregulating the expressions of HIF-1α, VEGF-A, bFGF, phospho-VEGFR2Tyr1175 and VEGFR2 and activating the phosphorylations of Akt and eNOS.

Sociability is fundamental for our daily life and is compromised in major neuropsychiatric disorders. However, the neuronal circuit mechanisms underlying prosocial behavior are still elusive. Here we identify a causal role of the basal forebrain (BF) in the control of prosocial behavior via inhibitory projections that disinhibit the midbrain ventral tegmental area (VTA) dopamine (DA) neurons. Specifically, BF somatostatin-positive (SST) inhibitory neurons were robustly activated during social interaction. Optogenetic inhibition of these neurons in BF or their axon terminals in the VTA largely abolished social preference. Electrophysiological examinations further revealed that SST neurons predominantly targeted VTA GABA neurons rather than DA neurons. Consistently, optical inhibition of SST neuron axon terminals in the VTA decreased DA release in the nucleus accumbens during social interaction, confirming a disinhibitory action. These data reveal a previously unappreciated function of the BF in prosocial behavior through a disinhibitory circuitry connected to the brain's reward system.

The results of recent animal studies have suggested that cochlear synaptopathy may be an important factor involved in presbycusis. Therefore, here, we aimed to examine whether cochlear synaptopathy frequently exists in patients with presbycusis and to describe the effect of cochlear synaptopathy on speech recognition in noise. Based on the medical history and an audiological examination, 94 elderly patients with bilateral, symmetrical, sensorineural hearing loss were diagnosed as presbycusis. An electrocochleogram, auditory brainstem responses, auditory cortical evoked potentials, and speech audiometry were recorded to access the function of the auditory pathway. First, 65 ears with hearing levels of 41-50 dB HL were grouped based on the summating potential/action potential (SP/AP) ratio, and the amplitudes of AP and SP were compared between the two resulting groups. Second, 188 ears were divided into two groups: the normal SP/AP and abnormal SP/AP groups. The speech recognition abilities in the two groups were compared. Finally, the relationship between abnormal electrocochleogram and poor speech recognition (signal-to-noise ratio loss ≥7 dB) was analyzed in 188 ears. The results of the present study showed: (1) a remarkable reduction in the action potential amplitude was observed in patients with abnormal SP/AP ratios; this suggests that cochlear synaptopathy was involved in presbycusis. (2) There was a large proportion of patients with poor speech recognition in the abnormal SP/AP group. Furthermore, a larger number of cases with abnormal SP/AP ratios were confirmed among patients with presbycusis and poor speech recognition. We concluded that cochlear synaptopathy is not uncommon among elderly individuals who have hearing ability deficits, and it may have a more pronounced effect on ears with declining auditory performance in noisy environments.

Dysfunction of long noncoding RNA (lncRNA) is associated with tumorigenesis of various malignancies, including glioma. Previously, lncRNA ARRDC1 antisense RNA 1(ARRDC1-AS1) has been reported to be dysregulated in several tumors. However, the roles of ARRDC1-AS1 in glioma have not been investigated. In this study, we firstly reported that ARRDC1-AS1 expression was distinctly increased in both glioma specimens and cell lines, and high ARRDC1-AS1 expression was associated with advanced clinical progression and poor prognosis of glioma patients. Additionally, STAT1 could activate the transcription of ARRDC1-AS1. Functional studies revealed that knockdown of ARRDC1-AS1 suppressed the proliferation, migration and invasion of glioma cells. Mechanisms exploration indicated ARRDC1-AS1 served as a sponge of miR-432-5p to upregulate PRMT5 expressions. Rescue experiments indicated that knockdown of miR-432-5p reversed the inhibiting effects of ARRDC1-AS1 knockdown on glioma cells. Overall, our findings highlighted the importance of STAT1/ARRDC1-AS1/miR-432-5p/PRMT5 axis in glioma progression and offered novel strategies for glioma treatments.

Berberine (BBR), a kind of quaternary ammonium benzylisoquinoline alkaloids with multiple pharmacological activities, has been regarded as a promising lipid-lowering agent in the field of drug repurposing. Particularly, the chemical modification at the C-9 position of BBR can remarkably improve its lipid-lowering efficacy. In this study, thirteen novel BBR derivatives were rationally designed, synthesized, and evaluated by preliminary pharmacological tests. The results showed that most compounds exhibited more potent hypolipidemic activities when compared with BBR and simvastatin. Among these compounds, compound 2h-1 and 2h-2 exhibited better activity profiling in these four tests involving with inhibition of total cholesterol (TCHO), triglyceride (TG), and low-density lipoprotein cholesterol (LDLC) and the increase of high-density lipoprotein cholesterol (HDLC). Correspondingly, the BBR analogs with 9-O-cinnamic moiety probably exhibited potent lipid-lowering activity, and should be exploited as an important versatile template for the development of BBR-like lipid-lowering agents.

Qiwei Tongbi oral liquid (QWTB), a classical traditional Chinese medicine (TCM) formula, has a good therapeutic effect on rheumatoid arthritis (RA) and is widely used in China. To comprehensively elucidate the therapeutic mechanism of QWTB in the treatment of RA, the effects of QWTB on biomarkers and metabolic pathways in a rat model of kidney deficiency arthritis were investigated in this study. The effects of QWTB on pharmacodynamic indicators, including paw swelling, arthritis score; interleukin-1β, interleukin-6, interleukin-17 F, tumor necrosis factor-α, tartrate-resistant acid phosphatase 5b, bone alkaline phosphatase, bone-specific alkaline phosphatase, bone glaprotein, urea, and creatinine levels; and histopathology, suggested that QWTB significantly improved renal function, inhibited the inflammatory response, and reduced bone loss. In total, 39 differential metabolites were screened by comparing the endogenous components between blank and model rat plasma, among which 16 metabolites were altered by QWTB. The metabolism pathway analysis revealed that α-linolenic acid metabolism, phenylalanine metabolism, sphingolipid metabolism, histidine metabolism and glycerophospholipid metabolism were greatly disturbed. Thus, the biomarkers investigated included (1) α-linolenic acid, (2) hippuric acid, (3) phosphatidylethanolamine (15:0/22:2(13Z,16Z)), (4) phenylpyruvic acid, (5) sphinganine, and (6) urocanic acid. QWTB affected three abnormal biomarkers: (3), (4), and (6). Phenylphruvic acid, sphinganine and urocanic acid were significantly associated with pharmacodynamic indicators, as shown by Pearson correlation analysis. These results indicated that RA-related biomarkers had certain reliability and biological significance. In summary, QWTB regulated the metabolic disorders in rats with RA. Its therapeutic mechanism may involve the regulation of phenylalanine metabolism, histidine metabolism, and glycerophospholipid metabolism. The results of this study are useful for understanding the therapeutic mechanisms of TCM.

Background: Benign paroxysmal positional vertigo (BPPV) is a self-limiting and recurrent disease but the cost is considerable. The number of patients with BPPV increased significantly under the quarantine policy in Hangzhou. The unhealthy lifestyle risk factors of BPPV have not yet been investigated. Thus, the objective is to analyze whether an unhealthy lifestyle is a risk factor of BPPV.Methods: One hundred and sixty three patients with idiopathic BPPV aged 22–87 years (BPPV group), and 89 aged 23–92 years sex-matched control subjects (non-BPPV group) were enrolled in this study. All BPPV patients received a definitive diagnosis which excluded secondary BPPV. Non-BPPV cases excluded BPPV, sudden deafness, Meniere's disease, ear or craniofacial surgery, vestibular neuritis, and head trauma history. We obtained a blood lipids profile, serum uric acid, total bilirubin, and related diagnostic information through the electronic medical record system. To get the time of physical activities and recumbent positions, we asked the patient or their family from February 2020 to June 2020, and the rest of the patient's information was acquired by phone or WeChat.Data Analyses: The t-test or chi-squared test, univariate, and multiple logistic regression analyses were performed for the two groups. For each factor, odds ratios were calculated with 95% confidence intervals (CIs). Moreover, test equality of two or more receiver operating characteristic (ROC) analyses were applied to the physical activities, and recumbent position time; area under curve (AUC) measures were calculated with 95% CIs and compared with each other.Results: The BPPV group had unhealthy lifestyles such as poor physical activities, prolonged recumbent position time, and low rate of calcium or VD supplementation in univariate logistic regression analyses (P < 0.05). Poor physical activities and prolonged recumbent position time were independently associated with BPPV in multiple logistic regression models (OR = 18.92, 95% CI: 6.34–56.43, p = 0.00 and OR = 1.15, 95% CI: 1.01–1.33, p < 0.04). In the comparison of ROC curves of recumbent position time and physical activities in identifying BPPV, AUCs were 0.68 (0.61–0.74), and 0.68 (0.63–0.73), respectively.Conclusion: We conclude that poor physical activities and prolonged recumbent position time may be independent risk factors for BPPV patients, but hypertension, hyperuricemia, hyperlipidemia, hemoglobin, diabetes, serum bilirubin, CHD, and CI, may not be.

Triptolide (TP) has shown potential in rheumatoid arthritis (RA) treatment, but the narrow therapeutic window limits its clinical application. In clinical practice, the compatibility of Tripterygium wilfordii and Paeonia lactiflora is often used to attenuate the toxicity of TP, but its compatibility mechanism has not been fully elucidated. The aim of this study was to investigate the pharmacokinetics and tissue distribution of a combined regimen of TP and paeoniflorin (PF) after transdermal administration in male and female Sprague Dawley (SD) rats via a rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The results showed that after percutaneous administration of TP and PF, there was no significant difference in AUC (0-t) (area under the curve) of TP, the peak concentration decreased by 58.17%, and the peak time was delayed. The AUC (0-t) of PF increased significantly ( P P P P

Microwave radiation was adopted to accelerate glycation between ovalbumin (OVA) and d-glucose. We evaluated the digestibility of glycated OVA from the perspective of kinetics, using pepsin and trypsin as model enzymes. Hydrolysed protein concentrations, enzymolysis kinetics, and activation energy (Ea) were investigated. The results showed that, under the conditions of simulating human digestion, the hydrolysis rate of OVA by pepsin was faster than that by trypsin, but for digestive enzymes, the digestion efficiency of OVA hydrolyzed by trypsin was higher. It was found that the rate constant of enzymatic hydrolysis of OVA was independent of the initial concentration of OVA but related to the type of protease and temperature. The reaction rate constants of glycated OVAs were significantly higher than that of native OVA during enzymolysis. Ea required for glycated OVA enzymatic hydrolysis by pepsin decreased, while that required by trypsin enzymatic hydrolysis nearly doubled. Liquid chromatography high-resolution mass spectrometry revealed that sample 1 had three glycated sites (R111, K227, and K264), sample 2 had two glycated sites (K207 and K323), sample 3 had five glycated sites (R127, R159, K227, R340, and K370), sample 4 had three glycated sites (R85, R143, and K323), and sample 5 had two glycated sites (R51 and R59). These sites increased Ea required for enzymatic hydrolysis of glycated OVA by trypsin.

Background: Benign paroxysmal positional vertigo (BPPV) is self-limiting and recurrent but the cost is considerable. The recurrence of BPPV increased significantly under the quarantine policy in Hangzhou. The unhealthy lifestyle risk factors of the recurrence of BPPV have not yet been investigated. So, the objective is to analyze the unhealthy lifestyle risk factors of recurrent BPPV.Methods: A retrospective observational study was conducted in the Department of Neurology in Tongde Hospital of Zhejiang Province from December 2018 to March 2020. The study included 186 patients aged 23–86 years. All patients received the definitive diagnosis and canalith repositioning maneuvers (CRM) treatment and finally accomplished follow-up for one year. Demographic variables, potential recurrence risk factors, neurological examination, cranial computed tomography and lifestyle were assessed.Data Analyses: The t-test or chi-squared test was first performed for group comparison, then logistic regression analysis was performed to investigate the recurrence risk factors in all of the patients.Results: The 1-year recurrence rates of BPPV patients after reposition maneuvers were 36.02%, is significantly higher than other study especially in the first quarter of 2020 (38.8% of patients with BPPV recurrence). Logistic regression analysis shows that BPPV patients who was poor physical activities and prolonged recumbent position time have more recurrence risks. Poor physical activities (odds ratio =5.690, 95% confidence interval: 1.650-19.618, p Conclusion: We conclude that poor physical activities and prolonged recumbent position time may be independent risk factors for the recurrence of BPPV patients, but aging, Ménière’s disease, sudden deafness migraine, hypertension, hyperlipemia, diabetes, CHD, POCI, mental factors, and mental labor do not increase the recurrence risk.

The absolute difference (phase jumping) between two adjacent phases should be less than pi in order to accurately recover the phase signal with traditional phase unwrapping algorithm, which limits the capability of quantitative measurement for traditional PHI-OTDR. In this article, a new process of phase unwrapping with an auxiliary light in coherent PHI-OTDR is proposed, so the resolvable phase jumping is extended to a larger value beyond pi and the capability of phase unwrapping is improved. In this PHI-OTDR system, wrapped differential phases between a reference position and the subsequent positions of fiber are firstly acquired for all probe light pulses. And wrapped differential phases of interleaving pulse sequence are unwrapped using the traditional phase unwrapping algorithm. Then, positions where the differential phases are correctly unwrapped are obtained from the discontinuously linear profile of the phase change curves of the original probe light. Based on these positions, the information of perturbation can be correctly retrieved. In experiment, the new process of phase unwrapping with the auxiliary for PHI-OTDR is executed and a perturbation signal which induces a maximum phase jumping of 3.7154 rad is well reconstructed. More experimental results all demonstrate the validity of the proposed method.

Aims The long-term impact of sodium glucose cotransporter 2 (SGLT2) inhibitors on renal functions remains undefined. This study was undertaken to investigate the renal outcomes associated with SGLT2 inhibitors in patients with type 2 diabetes (T2DM) in the long term. Methods A systematic literature search of PubMed and ClinicalTrials.gov was conducted. Randomized controlled trials which reported renal outcomes at the study endpoint in patients with T2DM receiving treatments of SGLT2 inhibitors were included. Renal adverse events were determined using prespecified lists from the Medical Dictionary for Regulatory Activities or laboratory values. Odds ratio with 95% confidence interval (CI) was used for assessment of dichotomous data. The mean difference or standardized mean difference with 95% CI was used for assessment of continuous data. Random effects models were adopted to measure the pooled outcomes. Results Thirty-nine studies involving 35 trials were identified. Compared with placebo or other anti-diabetic medications, SGLT2 inhibitors were associated with significant lower incidence of composite renal outcome and acute renal failure or injury in patients with T2DM. The risk of progression of albuminuria also appeared to be decreased. No significant changes of estimated glomerular filtration rate levels or urine albumin-creatinine ratios were found in patients receiving SGLT2 inhibitors. Conclusions Overall renal safety and beneficial effects are indicated for SGLT2 inhibitors. Further confirmative data from large trials and real-world studies are needed.

In the past few decades, environmental pollution problems have become more and more serious because of development of modern industry and science technology. The real-time detection and identification of atmospheric pollutants, has aroused widespread concern. Differential Absorption Lidar (DIAL) technology has become a common method for atmospheric remote sensing pollution measurement. 9~11-m-band lasers have small scattering cross sections for the air pollution cloud particles, so the laser output energy is required to reach the Joule level. The system engineering is difficult to realize detection of air pollution clouds with technology. The developed remote sensing pollution detection system is used to detect the types, concentration, orientation and distance information of common industrial chemical pollution. It is mainly divided into two parts: DIAL channel and Front Range Detecting Lidar (FRDL) channel. This paper mainly discusses remote sensing of air pollution clouds using FRDL. The working principle of FRDL is to use the Doppler effect of aerosol on the laser backward Mie scattering to realize the measurement of the aerosol cloud. In July 2017, the verification test was completed at a certain place in the north of China. The simulated pollutant spraying device and sampler were set at 400m in front of the 5km target. The measured results are in agreement with the actual situation.

Background Wound-related complications are an inevitable issue faced by spinal surgeons. Negative pressure drainage remains the most commonly used method to prevent postoperative hematoma and related complications. This prospective, randomized, controlled study was conducted to evaluate the efficacy of compression therapy following posterior lumbar interbody fusion, with emphasis on pain, anemia, and inflammation. Methods Sixty consecutive patients who have undergone posterior lumbar interbody fusion in the age range 43–78 years, with an average age of 59 years, were selected and randomly assigned into two groups. Factors, such as drainage volume, visual analog scale (VAS) pain score for back pain, white blood cell (WBC) count, red blood cell (RBC) count, hemoglobin (Hb) levels, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels assessed on the 1st, 3rd, and 10th days postoperatively, were compared between the two groups. Results The average follow-up was 6 months, ranging from 3 to 11 months. Drainage volume, VAS score, and CRP levels on the 10th day after the surgery were found to be significantly lower in the treatment group than in the control group. RBC count and Hb levels on the 3rd and 10th postoperative days were observed to be significantly higher in the treatment group than in the control group (P Conclusion Compression therapy relieves pain, alleviates anemia, and the inflammatory response following posterior lumbar interbody fusion. Trial registration ChiCTR1800015825 on chictr.org.cn, April 23, 2018, the trial registry is Chinese Clinical Trial Registry.

BackgroundIn locoregionally advanced nasopharyngeal carcinoma (LANPC) patients, variance of tumor response to induction chemotherapy (ICT) was observed. We developed and validated a novel imaging biomarker to predict which patients will benefit most from additional ICT compared with chemoradiotherapy (CCRT) alone.MethodsAll patients, including retrospective training (n = 254) and prospective randomized controlled validation cohorts (a substudy of NCT01245959,n = 248), received ICT+CCRT or CCRT alone. Primary endpoint was failure-free survival (FFS). From the multi-parameter magnetic resonance images of the primary tumor at baseline, 819 quantitative 2D imaging features were extracted. Selected key features (according to their interaction effect between the two treatments) were combined into an Induction Chemotherapy Outcome Score (ICTOS) with a multivariable Cox proportional hazards model using modified covariate method. Kaplan-Meier curves and significance test for treatment interaction were used to evaluate ICTOS, in both cohorts.ResultsThree imaging features were selected and combined into ICTOS to predict treatment outcome for additional ICT. In the matched training cohort, patients with a high ICTOS had higher 3-year and 5-year FFS in ICT+CCRT than CCRT subgroup (69.3% vs. 45.6% for 3-year FFS, and 64.0% vs. 36.5% for 5-year FFS; HR = 0.43, 95% CI = 0.25–0.74,p = 0.002), whereas patients with a low ICTOS had no significant difference in FFS between the subgroups (p = 0.063), with a significant treatment interaction (pinteraction n = 73, ICT+CCRT 89.7% and 89.7% vs. CCRT 61.8% and 52.8% at 3-year and 5-year; HR = 0.17, 95% CI = 0.06–0.51,p n = 175,p = 0.31), with a significant treatment interaction (pinteraction = 0.019). Compared with 12.5% and 16.6% absolute benefit in the validation cohort (3-year FFS from 69.9 to 82.4% and 5-year FFS from 63.4 to 80.0% from additional ICT), high ICTOS group in this cohort had 27.9% and 36.9% absolute benefit. Furthermore, no significant survival improvement was found from additional ICT in both groups after stratifying low ICTOS patients into low-risk and high-risks groups, by clinical risk factors.ConclusionAn imaging biomarker, ICTOS, as proposed, identified patients who were more likely to gain additional survival benefit from ICT+CCRT (high ICTOS), which could influence clinical decisions, such as the indication for ICT treatment.Trial registrationClinicalTrials.gov,NCT01245959. Registered 23 November 2010.

Analysis errors can occur in the desorbing process of ginkgo diterpene lactone meglumine injection (GDMI) by a conventional analysis method, due to several factors, such as easily crystallized samples, solvent volatility, time-consuming sample pre-processing, fixed method, and offline analysis. Based on risk management, near-infrared (NIR) and mid-infrared (MIR) spectroscopy techniques were introduced to solve the above problems with the advantage of timely analysis and non-destructive nature towards samples. The objective of the present study was to identify the feasibility of using NIR or MIR spectroscopy techniques to increase the analysis accuracy of samples from the desorbing process of GDMI. Quantitative models of NIR and MIR were established based on partial least square method and the performances were calculated. Compared to NIR model, MIR model showed greater accuracy and applicability for the analysis of the GDMI desorbing solutions. The relative errors of the concentrations of Ginkgolide A (GA) and Ginkgolide B (GB) were 2.40% and 2.89%, respectively, which were less than 5.00%. The research demonstrated the potential of the MIR spectroscopy technique for the rapid and non-destructive quantitative analysis of the concentrations of GA and GB.

Background Splenic artery pseudoaneurysm (SAP) around the pancreatic head causing obstructive jaundice is an extremely rare complication but can be life threatening once occurs. This case report is to raise awareness of this catastrophic complication and share our experience of successful endovascular management. Methods A 47-year-old male with a history of chronic pancreatitis clinically presented with epigastric pain and jaundice. Proximal SAP complicated with obstructive jaundice was confirmed by laboratory and imaging investigations. The SAP was successfully treated by transarterial coil embolization, and the jaundice subsequently improved. Results Abdominal contrast-enhanced computed tomography 11 months after embolization showed complete occlusion and reduction in the volume of the SAP as well as normal biliary tract. Conclusions SAP complicated with obstructive jaundice should be managed timeously and aggressively once diagnosed, given its potential adverse consequences. Transarterial embolization using the isolation technique may be a safe and effective strategy for treating this disease.

Ginkgo diterpene lactones meglumine injection (GDLI) is a commercially available product used for neuroprotection. However, the pharmacokinetic properties of the prototypes and hydrolyzed carboxylic forms of the primary components in GDLI, i.e., ginkgolide A (GA), ginkgolide B (GB), and ginkgolide K (GK), have never been fully evaluated in beagle dogs. In this work, a simple, sensitive, and reliable method based on ultra-fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) was developed, and the prototypes and total amounts of GA, GB, and GK were determined in beagle dog plasma. The plasma concentrations of the hydrolyzed carboxylic forms were calculated by subtracting the prototype concentrations from the total lactone concentrations. For the first time, the pharmacokinetics of GA, GB, and GK were fully assessed in three forms, i.e., the prototypes, the hydrolyzed carboxylic forms, and the total amounts, after intravenous administration of GDLI in beagle dogs. It was shown that ginkgolides primarily existed in the hydrolyzed form in plasma, and the ratio of hydrolysates to prototype forms of GA and GB decreased gradually to a homeostatic ratio. All of the three forms of the three ginkgolides showed linear exposure of AUC to the dosages. GA, GB, and GK showed a constant half-life approximately 2.7, 3.4, and 1.2 h, respectively, which were consistent for the forms at three dose levels (0.3, 1.0, and 3.0 mg·kg-1) and after a consecutive injection of GDLI for 7 days (1.0 mg·kg-1).