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The ongoing COVID-19 pandemic is causing huge impact on health, life, and global economy, which is characterized by rapid spreading of SARS-CoV-2, high number of confirmed cases and a fatality/case rate worldwide reported by WHO. The most effective intervention measure will be to develop safe and effective vaccines to protect the population from the disease and limit the spread of the virus. An inactivated, whole virus vaccine candidate of SARS-CoV-2 has been developed by Wuhan Institute of Biological Products and Wuhan Institute of Virology. The low toxicity, immunogenicity, and immune persistence were investigated in preclinical studies using seven different species of animals. The results showed that the vaccine candidate was well tolerated and stimulated high levels of specific IgG and neutralizing antibodies. Low or no toxicity in three species of animals was also demonstrated in preclinical study of the vaccine candidate. Biochemical analysis of structural proteins and purity analysis were performed. The inactivated, whole virion vaccine was characterized with safe double-inactivation, no use of DNases and high purity. Dosages, boosting times, adjuvants, and immunization schedules were shown to be important for stimulating a strong humoral immune response in animals tested. Preliminary observation in ongoing phase I and II clinical trials of the vaccine candidate in Wuzhi County, Henan Province, showed that the vaccine is well tolerant. The results were characterized by very low proportion and low degree of side effects, high levels of neutralizing antibodies, and seroconversion. These results consistent with the results obtained from preclinical data on the safety.

Anterior commissure (AC) involvement is an unfavorable factor for transoral laser microsurgery (TLM) treatment of early glottic carcinoma (EGC). This study aimed to evaluate the therapeutic efficacy of TLM treatment for EGC with AC involvement.From 2008 to 2017, 177 patients with T1-T2 EGC with AC involvement were retrospectively included and divided into the TLM group (n=115) receiving COThe TLM group had significantly reduced hospital stay, hospitalization costs, and intraoperative blood loss as compared with the control group. The tracheotomy rate was significantly higher in the control group (96.8% vs. 0%). The 5-year overall survival (OS) was 89.6% and 85.5% in the TLM group and control group, respectively. Log-rank test showed no difference in survival rate between the two groups. There was no significant difference in laryngeal preservation rate and overall recurrence rate between groups. In postoperative vocal function evaluation, there were significant differences in the overall grade (G), the roughness (R), the breathiness (B), Voice Handicap Index-10 (VHI-10), Jitter, Shimmer, noise/harmonic ratio (NHR), maximum phonation time (MPT), phonation threshold pressure (PTP) between the two groups.For EGC with AC involvement, TLM has similar survival outcomes with the open surgery, but has better postoperative voice outcomes. Meanwhile, TLM can effectively reduce intraoperative blood loss, hospitalization time, hospitalization costs and postoperative complications.

To observe the effect of wheat-grain moxibustion at "Dazhui" (GV 14) on the expressions of Beclin-1 and GRP78 in spinal dorsal horn in rats with cervical spondylotic radiculopathy (CSR), and to explore the possible analgesic mechanism of wheat-grain moxibustion for CSR.A total of 48 SD rats were randomly divided into a sham operation group, a model group, a wheat-grain moxibustion group and a wheat-grain moxibustion+3-MA group, 12 rats in each group. The CSR model was prepared by spinal cord insertion method. Three days after modeling, the rats in the model group were intraperitoneally injected with 1 mL of 0.9% sodium chloride solution; the rats in the wheat-grain moxibustion group were treated with wheat-grain moxibustion at "Dazhui" (GV 14, 6 cones per time) on the basis of the model group; the rats in the wheat-grain moxibustion+3-MA group were intraperitoneally injected with 3-MA solution and wheat-grain moxibustion at "Dazhui" (GV 14, 6 cones per time). The three groups were intervened for 7 days, once a day. The gait score and mechanical pain threshold were observed before treatment and 7 days into treatment; after the treatment, the expressions of mRNA and protein of Beclin-1 in spinal dorsal horn were detected by real-time fluorescence quantitative PCR and immunohistochemistry; the expression of GRP78 protein in spinal dorsal horn was detected by Western blot method; the autophagosomes and ultrastructure in spinal dorsal horn neurons were observed by electron microscope.After the treatment, compared with the sham operation group, in the model group, the gait score was increased and the mechanical pain threshold was decreased (Wheat-grain moxibustion at "Dazhui" (GV 14) has analgesic effect on CSR rats. The mechanism may be related to moderately up-regulate the expression of Beclin-1, enhance autophagy and reduce endoplasmic reticulum stress.

Dangerous driving, e.g., using mobile phone while driving, can result in serious traffic problem and threat to safely. To efficiently alleviate such problem, in this paper, we design a intelligent monitoring system to detect the dangerous behavior in driving. The monitoring system is combined by camera, terminal server, target detection algorithm and voice reminder. Furthermore, we applied an efficiently deep learning model, namely mobilenet combined with single shot multi-box detector (mobilenet-SSD), to identify the behavior of driver. To evaluate the performance of proposed system, we construct a dangerous driving dataset which consists of 6796 images. The experimental results show that the proposed system can achieve accuracy of 99% in 100 testing images. It can be used for real-time monitoring of the driver’s status.

PURPOSE Few studies have explored the biomarkers for predicting the heterogeneous outcomes of patients with advanced pancreatic adenocarcinoma showing stable disease (SD) on the initial postchemotherapy computed tomography. We aimed to devise a radiomics signature (RS) to predict these outcomes for further risk stratification. MATERIALS AND METHODS Patients with advanced pancreatic adenocarcinoma and SD after chemotherapy were included. Pancreatic lesions on initial postchemotherapy computed tomography images were evaluated by radiomics analysis for predicting early death (≤ 1 year). RS was then internally and externally tested. The progression-free survival and objective response rate were compared between the low-risk and high-risk group of patients classified following RS. RESULTS Approximately 62.7% of patients receiving chemotherapy showed SD at first response evaluation in the primary cohort, which were 59.6% and 57.9% in internal and external testing cohorts, respectively. The RS predicted 1-year overall survival well, with areas under the receiver operating characteristic curve of 0.91 in the training cohort, 0.90 in the validation cohort, 0.84 in the internal testing cohort, and 0.87 in the external testing cohort. The high-risk group had a shorter median progression-free survival (7.3 months v 9.0 months, P = .016, in the training cohort; 5.9 months v 9.2 months, P = .026, in the internal testing cohort) and a lower objective response rate (2.2% v 24.0% in the training cohort) than the low-risk group. In addition, RS was not related to the clinical characteristics and chemotherapy regimens. CONCLUSION RS independently predicts the outcomes of patients with SD after chemotherapy well and can help to improve treatment decisions by identifying patients for whom current treatment may not be suitable.

N6-Methyladenosine (m6A), one of the post-transcriptional modifications of RNA, is important in hepatocellular carcinoma (HCC). However, the mechanism of its regulation remains elusive. We here show that exposure of HCC cells to sulfatide significantly reduced the total mRNA m6A modification. Interestingly, METTL3 protein was robustly acetylated and the binding of METTL3 to MTF1 mRNA, METTL14 or WTAP was weakened in cells treated with sulfatide. Further investigation of the METTL3 complex revealed recruitment of the deacetylase scaffold SIN3B, but a diminished level of histone deacetylase HDAC2, which might enhance the acetylation of METTL3. The m6A abundance in MTF1 mRNA was markedly decreased in cells after sulfatide treatment. The expression of MTF1, a zinc-dependent transcription factor, was significantly strengthened with reduced m6A modification. Sulfatide prolonged the half-life of MTF1 mRNA, while the mutation (A to C) on 7 methylation sites in the 3'UTR of MTF1 mRNA enhanced MTF1 mRNA stability. 3-deaza-adenosine, an m6A methylation inhibitor, significantly reduced the m6A modification of MTF1 mRNA but extended its half-life time. Importantly, overexpression of MTF1 prompted HCC cell proliferation and was associated with poor prognosis. In conclusion, the METTL3-METTL14-WTAP complex was regulated by acetylation induced by sulfatide to control MTF1 m6A methylation and its mRNA transcription, which was important for the tumor growth and migration of HCC.

To observe the effect of mild moxibustion (Moxi) at "Dazhui" (GV14) on neuropathic pain, expression of autophagy and apoptosis factor LC3 and Bax proteins and mRNAs in the spinal cord tissue in rats with cervical spondylotic radiculopathy (CSR), so as to explore its underlying mechanism underlying relief of CSR-induced pain.Forty rats (half male half female) were randomly divided into blank control, model, Moxi, Moxi+autophagy inhibitor 3-methyladenine (3-MA, Moxi+3-MA) groups, with 10 rats in each group. The CSR model was established by loose ligature of the local cervical nerve roots. Three days after modeling, mild Moxi was applied to GV14 for 10 min, once daily for 7 days. Rats of the Moxi+3-MA group received intraperitoneal injection of 3-MA(1 mL, 15 mg/kg+ saline) before Moxi, once daily for 7 consecutive days. Rats of the model and Moxi groups were also given normal saline (i.p., 1 mL), once daily for 7 days. The gait behavior score (1-3 points) was scaled according to the rats' pain reaction and foot paw contracture produced walking disorder and the mechanical pain threshold (MPT) was detected before and after the treatment. The expression of spinal cord LC3 and Bax proteins and mRNAs were detected by immunohistochemistry and quantitative RT-PCR, respectively.Compared with the blank control group, the gait disorder score, and percentage of Bax positive cells and expression of Bax mRNA were significantly increased (Mild Moxi at GV14 can relieve neuropathic pain in CSR rats, which may be related to its functions in up-regulating LC3 autophagy, thereby inhibiting the expression of Bax pro-apoptotic protein in spinal cord to reduce apoptosis and to repair nerve injury.

Direct moxibustion (DM) is reported to be useful for cervical spondylotic radiculopathy (CSR), but the analgesic mechanism remains unknown. Autophagy plays a protective role in neuronal apoptosis, Act A/Smads signaling pathway has been confirmed to be associated with the activation of autophagy. The study aimed to explore the effect of DM on autophagy in rats with CSR and the involvement of Act A/Smads signaling pathway.Rats were randomly divided into Sham, CSR, CSR + DM, CSR + DM + 3-MA (PI3K inhibitor), and CSR + DM + SB (Act A inhibitor) group. Three days after establishment of CSR model with a fish line inserted under the axilla of the nerve roots, DM at Dazhui (GV14) was performed six times once for seven consecutive days. Western blot and immunofluorescence staining were used to observe the expression of the neuronal autophagy molecule LC3II/I, Atg7, and Act A/Smads signaling molecule Act A, p-Smad2, and p-Smad3. Bcl-2/Bax mRNA expression was measured by real time PCR.DM improved the pain threshold and motor function of CSR rats and promoted the expression of Act A, p-Smad2, p-Smad3, LC3II/I, and Atg7 in the entrapped-nerve root spinal dorsal horn. DM reduced the expression of Bax mRNA and decreased the number of apoptotic neurons. 3-MA and Act A inhibitor SB suppressed the expression of above-mentioned proteins and reduced the protective effect of DM on apoptotic neurons.DM exerts analgesic effects by regulating the autophagy to reduce cell apoptosis and repair nerve injury, and this feature may be related to the Act A/Smads signaling pathway.

To investigate the clinicopathological and molecular features of colorectal cancer (CRC) with synchronous adenoma and to describe features of synchronous adenomas in CRC patients.Single-centre retrospective cohort of 180 patients were included. The clinicopathological and endoscopic data were collected. The expression mismatch repair (MMR) proteins were detected by immunohistochemistry. The determination of microsatellite instability (MSI) was performed by multiple fluorescence PCR, and the mutations of genes were detected by real-time PCR.Among all cases, 49 were diagnosed as CRC with synchronous adenoma, and 131 were diagnosed as solitary CRC. Some of the differences between the groups are: higher incidence was found in male (71.4 vs. 52.6%,Gender, a habit of drinking and other neoplastic diseases are risk factors for the development of a synchronous adenoma. With a low rate of BRAF mutations, the responses to monoclonal antibody and prognosis of patients with synchronous adenomas may be better than that of solitary CRC.

Data on average iodine requirements for the Chinese population are limited following implementation of long-term universal salt iodisation. We explored the minimum iodine requirements of young adults in China using a balance experiment and the ‘iodine overflow’ hypothesis proposed by our team. Sixty healthy young adults were enrolled to consume a sequential experimental diet containing low, medium and high levels of iodine (about 20, 40 and 60 μg/d, respectively). Each dose was consumed for 4 d, and daily iodine intake, excretion and retention were assessed. All participants were in negative iodine balance throughout the study. Iodine intake, excretion and retention differed among the three iodine levels (P < 0·01 for all groups). The zero-iodine balance derived from a random effect model indicated a mean iodine intake of 102 μg/d, but poor correlation coefficients between observed and predicted iodine excretion (r 0·538 for μg/d data) and retention (r 0·304 for μg/d data). As iodine intake increased from medium to high, all of the increased iodine was excreted (‘overflow’) through urine and faeces by males, and 89·5 % was excreted by females. Although the high iodine level (63·4 μg/d) might be adequate in males, the corresponding level of 61·6 μg/d in females did not meet optimal requirements. Our findings indicate that a daily iodine intake of approximately half the current recommended nutrient intake (120 μg/d) may satisfy the minimum iodine requirements of young male adults in China, while a similar level is insufficient for females based on the ‘iodine overflow’ hypothesis.

The platysma skin flap was used for laryngeal reconstruction after vertical partial laryngectomy to improve the postoperative voice quality of patients with T2 and T3 glottic laryngeal carcinoma. Sixty-nine patients with unilateral T2 and T3 glottic laryngeal carcinoma were included. Forty-six patients received vertical partial laryngectomy, and a platysma skin flap was used for laryngeal reconstruction. The other 23 patients underwent transoral laser microsurgery. Subjective and objective examinations were performed to evaluate laryngeal morphology after the surgery. Acceptable voice quality was achieved for 46 patients who underwent vertical partial laryngectomy. Flap vibrational waves occurred in 19 cases (41.3%). The platysma skin flap is an ideal tissue for the reconstruction of articulation structure in open surgery of T2 and T3 unilateral glottic laryngeal carcinoma.

Undifferentiation is a key feature of nasopharyngeal carcinoma (NPC), which presents as a unique opportunity for intervention by differentiation therapy. In this study, we found that SOX1 inhibited proliferation, promoted differentiation, and induced senescence of NPC cells, which depended on its transcriptional function. RNA-Seq-profiling analysis showed that multiple undifferentiated markers of keratin family, including KRT5, KRT13, and KRT19, were reduced in SOX1 overexpressed NPC cells. Interestingly, gene ontology (GO) analysis revealed genes in SOX1 overexpressed cells were enriched in extracellular functions. The data of LC/MS untargeted metabolomics showed that the content of retinoids in SOX1 overexpressed cells and culture medium was both higher than that in the control group. Subsequently, we screened mRNA level of genes in retinoic acid (RA) signaling or metabolic pathway and found that the expression of UDP-glucuronosyltransferases was significantly decreased. Furtherly, UGT2B7 could rescue the differentiation induced by SOX1 overexpression. Inhibition of UGTs by demethylzeylasteral (T-96) could mimic SOX1 to promote the differentiation of NPC cells. Thus, we described a mechanism by which SOX1 regulated the differentiation of NPC cells by activating retinoid metabolic pathway, providing a potential target for differentiation therapy of NPC.

Objectives: To assess long-term (2-year) biologic treatment patterns of psoriatic arthritis (PsA) patients who initiated adalimumab, certolizumab pegol, etanercept, golimumab, or ustekinumab.Method...

Aim and Objective: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a common chronic kidney disease that leads to End-Stage Renal Disease (ESRD). The key target of this therapy is to prevent the progression of kidney failure. Tolvaptan could slow kidney cyst growth and are proven highly effective. The aims of this analysis are to perform a systematic review, estimate and evaluate the efficacy and safety of tolvaptan in ADPKD patients. Materials and Methods: Randomized controlled trials of tolvaptan in ADPKD were identified in PubMed, Ovid, Web of Science and the Cochrane Library electronic database. The changes observed in kidney function, treatment efficiency and the incidence of adverse events between the tolvaptan and placebo groups were compared. Data were analyzed by the RevMan software. Results: Eight trials, including 7 double-blinded randomised controlled trials and 1 quasi RCT involving 1,536 patients were extracted. Significant differences in the annual rate of change in the total kidney volume TKV at any stages of CKD (MD = -3.32, 95%CI =-4.57,-2.07, I2 =70%) and the glomerular filtration rate (MD = 1.4, 95%CI = 0.83,1.97, I2 =0%) were observed between the tolvaptan group and the placebo group. Subgroup analysis of patients in different CKD stages also showed the same conclusion. There was an increase in the urine osmolality, and 24-hour urine volume in patients receiving tolvaptan. Tolvaptan reduced the rate of serious hypertension and kidney pain events in ADPKD patients. At higher doses, it increased the rate of adverse events (liver injuries, thirst, pollakiuria, and nocturia). There was no significant risk of bias in the included studies. Conclusions: Tolvaptan has a beneficial effect on ADPKD, but is associated with an increase in adverse events at high doses when compared with the placebo. Further RCTs on tolvaptan may be required to support this conclusion.

Although there has been increasing interest in aesthetical approaches for treating patients with papillary thyroid carcinoma (PTC), there have been no studies comparing the safety and effectiveness of gasless endoscopic selective lateral neck dissection (SLND) via the anterior chest approach (ACA) with that of conventional open surgery (OPEN) for papillary thyroid carcinoma. A total of 91 patients with PTC who underwent either gasless endoscopic thyroidectomy, central compartment neck dissection and SLND via the ACA or conventional open surgery between Nov. 2008 to Dec. 2018 were included. Primary outcomes and demographic data were compared between the two groups. Thirty-one patients were in the ACA group and 60 were in the OPEN group. The ACA group was younger and had a longer operative time but less intraoperative hemorrhage (P

The TS-1 particles grown on carbon nanotubes decorated nickel foam (denoted as MTS-1S) are successfully synthesized by a steam-assisted crystallization method that does not waste the gels and is mo...

Acute kidney injury (AKI) is a common clinical complication associated with high mortality in patients. Immune cells and cytokines have recently been described to play essential roles in AKI pathogenesis. Plasmacytoid dendritic cells (pDCs) are a unique DC subset that specializes in type I interferon (IFN) production. Here, we showed that pDCs rapidly infiltrated the kidney in response to AKI and contributed to kidney damage by producing IFN-α. Deletion of pDCs using DTR(BDCA2) transgenic (Tg) mice suppressed cisplatin-induced AKI, accompanied by marked reductions in proinflammatory cytokine production, immune cell infiltration and apoptosis in the kidney. In contrast, adoptive transfer of pDCs during AKI exacerbated kidney damage. We further identified IFN-α as the key factor that mediated the functions of pDCs during AKI, as IFN-α neutralization significantly attenuated kidney injury. Furthermore, IFN-α produced by pDCs directly induced the apoptosis of renal tubular epithelial cells (TECs) in vitro. In addition, our data demonstrated that apoptotic TECs induced the activation of pDCs, which was inhibited in the presence of an apoptosis inhibitor. Furthermore, similar deleterious effects of pDCs were observed in an ischemia reperfusion (IR)-induced AKI model. Clinically, increased expression of IFN-α in kidney biopsies was observed in kidney transplants with AKI. Taken together, the results of our study reveal that pDCs play a detrimental role in AKI via IFN-α.

Molybdenum carbide (Mo2C), a member of transition metal carbides (TMCs), has shown promise in water splitting. Although excellent hydrogen evolution reaction (HER) performance of Mo2C has been achieved both in acid and basic media, the intrinsic hydrogen evolution ability of two-dimensional (2D) Mo2C is still not clear due to the difficulty of calculating the actual active surface area involved in the HER. In this work, the HER activity of Mo2C nanosheets is measured on single 2D Mo2C, which is synthesized through low-temperature carbonization of 2D molybdenum dioxide (MoO2) nanosheets on a SiO2/Si substrate. The edge sites of Mo2C exhibit high catalytic activity with a small Tafel slope of 40.2 mV dec−1 and an overpotential of 152 mV for 10 mA cm−2 in alkaline media. Theoretical analyses reveal that the energy barriers for cleaving the OH–H bond in H2O on the edge of Mo2C are much smaller than those on the basal plane of Mo2C and the Mo site of the edge of Mo2C displays the optimal ΔGH for the H absorption.

Organic–inorganic hybrid perovskite nanowires with well-defined structures have attracted considerable attention for optoelectronic applications. Perovskite nanowires integrated into practical optoelectronic devices are often hindered by the poor crystalline quality. Herein, a ligand-assisted reprecipitation (LARP) strategy is employed to prepare ultralong and freestanding CH3NH3PbI3 nanowires on a large-scale. Oleylamine is adopted as an inhibitor, which can create a passivation layer on the surface of CH3NH3PbI3, to slow down the crystallization rate of CH3NH3PbI3 nanowires. With the low crystallization rate, several millimeters long and high-quality CH3NH3PbI3 nanowires with smooth surfaces can be synthesized on a large scale. Photodetectors fabricated on oleylamine assisted synthesized CH3NH3PbI3 nanowires exhibit high detectivity, which is five times higher than that of non-oleylamine assisted synthesized CH3NH3PbI3 nanowire photoanodes.

Hawthorn including many plants from the genus Crataegus (C.) is used for traditional medicines, herbal drugs, and dietary supplements all over the world. In China, C. pinnatifida Bge. var. major N, E. Br, and C. pinnatifida Bge. are two major species that are used as hawthorn. The purpose of this study is to assay the myocardial protection of hawthorn fruit processed with honey (MSZ) and screen the chemical basis of MSZ on this effect. Firstly, ultra-performance liquid chromatography-quadrupole time of flight-mass spectrometry (UPLC/Q-TOF-MS) was used to analyze the chemical constituents of the sliced dry fruit of hawthorn (SZ) and MSZ. Principal component analysis (PCA) was used to differentiate them. Orthogonal partial least squares-discriminate analysis (OPLS-DA) was applied to screen different compounds between SZ and MSZ, and 32 different compounds were selected. Then a pharmacodynamic test to investigate their protective effect against myocardial ischaemia was carried out. The results demonstrated that the protective effect of MSZ was better than that of SZ on the same dose. Finally, the chemical basis for the protective effect provided by MSZ against myocardial ischaemia was speculated based on correlation analysis. Taken together, all these results suggest that phenylpropanoids, organic acids, tannins, and flavonoids might be the chemical basis of MSZ protecting against myocardial ischaemia.

Transition metal dichalcogenides (TMDs), such as molybdenum diselenide (MoSe2), have poor alkaline hydrogen evolution activities due to their unfavorable hydrogen adsorption and dissociation properties. In this work, we report a Mo2C/MoSe2 hybrid catalyst seamlessly grown on Mo foil. The Mo2C/MoSe2/Mo electrode exhibits outstanding activity for the hydrogen evolution reaction (HER) with a low overpotential of 51 mV at 10 mA cm−2 in 1 M KOH, significantly outperforming the performances of its MoSe2 and Mo2C counterparts and most reported TMD electrocatalysts in alkaline solution. Moreover, the Mo2C/MoSe2/Mo electrode also possesses good catalytic HER performance in acid. Density functional theory (DFT) calculations reveal that metal-induced gap states formed in the interface region of Mo2C and MoSe2 can make the interfacial semiconducting MoSe2 transform into metallic MoSe2. The transformation is beneficial to speeding up charge transfer between the interfaces, promoting H atom adsorption and desorption kinetics, and therefore enhancing the catalytic performance.

Despite the increasing number of inflammatory bowel disease (IBD) patients using traditional Chinese medicine (TCM), relatively few studies have examined their experiences with TCM in the Chinese healthcare context. The aim of this study was to explore these experiences from the perspective of IBD patients. Adopting a qualitative descriptive method, IBD patients from several comprehensive hospitals in Hangzhou, Zhejiang were recruited through purposive sampling. Data were collected using semistructured interviews and analyzed by a conventional content analysis method. The results are presented thematically. Fourteen IBD patients participated in the study. They often used TCM, such as Chinese herbal medicine, retention enemas of Chinese medicine, and acupuncture, as a complementary therapy instead of as an alternative to conventional therapies. Three themes emerged from the analysis: triggers for initiating TCM, the experienced efficacies of TCM, and disturbances caused by TCM use. The IBD patients initiate TCM treatment due to the unsatisfactory effects of conventional therapies and TCM culture. However, the efficacies of TCM are subjective and slow acting and vary across individuals. There are communication gaps between physicians and patients concerning TCM. Thus, healthcare professionals are encouraged to gain more knowledge on these therapies and employ a participatory decision-making style based on this understanding.

Mitochondrial defects are a hallmark of early pathophysiology in Alzheimer's disease, with pathologically phosphorylated tau reported to induce mitochondrial toxicity. Mitophagy constitutes a key pathway in mitochondrial quality control by which damaged mitochondria are targeted for autophagy. However, few details are known regarding the intersection of mitophagy and pathologies in tauopathy. Here, by applying biochemical and cell biological approaches including time-lapse confocal imaging in live tauopathy neurons, combined with gene rescue experiments via stereotactic injections of adeno-associated virus particles into tauopathy mouse brains, electrophysiological recordings and behavioural tests, we demonstrate for the first time that mitochondrial distribution deficits at presynaptic terminals are an early pathological feature in tauopathy brains. Furthermore, Parkin-mediated mitophagy is extensively activated in tauopathy neurons, which accelerates mitochondrial Rho GTPase 1 (Miro1) turnover and consequently halts Miro1-mediated mitochondrial anterograde movement towards synaptic terminals. As a result, mitochondrial supply at tauopathy synapses is disrupted, impairing synaptic function. Strikingly, increasing Miro1 levels restores the synaptic mitochondrial population by enhancing mitochondrial anterograde movement and thus reverses tauopathy-associated synaptic failure. In tauopathy mouse brains, overexpression of Miro1 markedly elevates synaptic distribution of mitochondria and protects against synaptic damage and neurodegeneration, thereby counteracting impairments in learning and memory as well as synaptic plasticity. Taken together, our study reveals that activation of the Parkin pathway triggers an unexpected effect-depletion of mitochondria from synaptic terminals, a characteristic feature of early tauopathy. We further provide new mechanistic insights into how parkin activation-enhanced Miro1 degradation and impaired mitochondrial anterograde transport drive tauopathy-linked synaptic pathogenesis and establish a foundation for future investigations into new therapeutic strategies to prevent synaptic deterioration in Alzheimer's disease and other tauopathies.

This study aimed to illustrate the association of four major chronic noncommunicable diseases (cardiovascular diseases, cancer, respiratory diseases, and diabetes) with life expectancy (LE) of Chinese residents in 2019 and to provide an evidence base for the scientific prevention and treatment of chronic diseases in China. The abbreviated life and cause-eliminated life tables were compiled according to the Jiang Qing Lang method recommended by WHO (World Health Organization) to calculate LE and cause-eliminated life expectancy (CELE) in 2019. The disease that had the greatest association with the LE of Chinese residents was cardiovascular disease (CVD), with the LE increasing by 8.13 years after removing CVD deaths. This was followed by cancer (2.68 years), respiratory diseases (0.88 years), and diabetes (0.24 years). The four major chronic noncommunicable diseases (NCDs) were the main diseases affecting the health of Chinese residents. CVD should be prevented and treated as the key disease among the chronic diseases, while women and rural people should be the major focus of health knowledge promotion. All residents should be encouraged to develop a good understanding of self-protection and of how to achieve a healthy lifestyle in order to reduce the occurrence of death and to improve their quality of life and health in general.

Desmoplasia is a hallmark of intrahepatic cholangiocarcinoma (ICC), which constitutes a barrier to infiltration of lymphocyte, but not myeloid cells. Given that dense desmoplastic stroma has been reported to be a barrier to infiltration of lymphocyte, but not myeloid cells. We here investigated whether fibroblastic FAP influenced ICC progression via non-T cell-related immune mechanisms. We demonstrated fibroblastic FAP expression was critical for STAT3 activation and CCL2 production, and ICC-CAFs were the primary source of CCL2 in human ICC microenvironment by using ICC-Fbs from six ICC patients. Fibroblastic knockdown of FAP significantly impaired the ability of ICC-CAFs to promote ICC growth, MDSCs infiltration and angiogenesis, which was restored by adding exogenous CCL2. Furthermore, interestingly, the tumor-promoting effect of fibroblastic FAP is dependent on MDSCs via secretion of CCL2, as depletion of Gr-1+ cells reversed the restoring effects of exogenous CCL2 on tumor growth and angiogenesis. In vitro migration assay confirmed that exogenous CCL2 could rescue the impaired ability of ICC-Fbs to attract Gr-1+ cells caused by fibroblastic FAP knockdown. In contrast, fibroblastic FAP knockdown had no effect on ICC cell proliferation and apoptotic resistance. Depletion MDSCs by anti-Gr-1 monoclonal antibody in subcutaneous transplanted tumor model abrogated tumor promotion by ICC-CAFs suggested that the pro-tumor function of Fibroblastic FAP relied on MDSCs. Mechanical, flow cytometry and chamber migration assay were conducted to find Fibroblastic FAP was required by the ability of ICC-CAFs to promote MDSC migration directly. Moreover, fibroblastic FAP knockdown had no effect on cell proliferation and apoptotic resistance. Here, we revealed the T-cell independent mechanisms underlying the ICC-promoting effect of fibroblastic FAP by attracting MDSCs via CCL2, which was mainly attributed to the ability of FAP to attract MDSCs and suggests that specific targeting fibroblastic FAP may represent a promising therapeutic strategy against ICC.

Background To explore the therapeutic effect of topical 5-Aminolevulinic Acid photodynamic therapy (ALA-PDT) on laryngeal papillomatosis (LP) treatment. Methods 13 patients with LP underwent topical ALA-PDT after tumor resection (CO2laser or/and microdebrider resection). All patients were irradiated 3–4 times. After ALA-PDT treatment, the laryngoscopic examination was performed every 1–2 months to observe the therapeutic effect. Results All 13 patients were followed up for more than 1 year. Eleven cases (84.6%) showed no recurrence; two cases (15.4%) had relapses. One child developed III° inspiratory dyspnea caused by laryngeal mucosal edema and need endotracheal intubation again. Four patients had adhesion of the anterior commissure of the vocal cord. The detection rate of HPV infections was 76.9% and two patients had multiple HPV subtype co-infection. Conclusions The preliminary effect of topical ALA-PDT significantly reduces recurrence and improves the cure rate of LP. Further research on this treatment is still required.

Enhancing glucagon-like peptide 1 (GLP-1) signaling with a dipeptidyl peptidase IV (DPP-4) inhibitor might exert protective effects on Alzheimer's disease (AD). We found that intragastric administration of Gramcyclin A (10, 20 and 40 mg/kg), a novel DPP-4 inhibitor, for 3 months significantly reversed cognitive decline in APP/PS1/tau triple transgenic mice in a dose-dependent manner. Gramcyclin A treatment markedly reduced Aβ plaques as well as the insoluble and soluble forms of Aβ40 and Aβ42 in the hippocampus of APP/PS1/tau mice. Treatment with Gramcyclin A remarkedly decreased the level of microglia and suppressed neuroinflammation in the hippocampus of APP/PS1/tau mice. Moreover, Gramcyclin A treatment could increase brain glucose uptake in APP/PS1/tau mice, as detected by 18-fluoro-2-deoxyglucose (

To compare the clinical effect of acupuncture combined with wheat-grain moxibustion and oral sertraline hydrochloride dispersible tablets in the treatment of mild to moderate postpartum depression.Sixty patients with mild to moderate postpartum depression were randomly divided into an observation group and a control group, 30 cases in each group. Both groups were treated with psychotherapy. The control group was treated with oral sertraline hydrochloride dispersible tablets, 50 mg each time, once a day; the observation group was treated with acupuncture at Qihai (CV 6), Zusanli (ST 36), Xuehai (SP 10), Hegu (LI 4), Sanyinjiao (SP 6), Taixi (KI 3), etc. combined with wheat-grain moxibustion at Xinshu (BL 15), Pishu (BL 20), Ganshu (BL 18) and Shenshu (BL 23), once every other day, 3 times a week. Both groups were treated for 4 weeks as a course, with 2 consecutive courses of treatment. Before and after treatment and follow-up of 3 months after the end of treatment, the Hamilton depression scale (HAMD), Edinburgh postnatal depression scale (EPDS) and World Health Organization quality of life-BREF (WHOQOL-BREF) score of the two groups were compared, and the clinical effect was assessed.After treatment and during follow-up, the HAMD and EPDS scores of the two groups were lower than before treatment (Acupuncture combined with wheat-grain moxibustion can improve the depressive symptoms of patients with mild to moderate postpartum depression and improve their quality of life, and the clinical effect is more lasting and stable than oral sertraline hydrochloride dispersible tablets.

ObjectiveTo assess annual healthcare resource utilization including inpatient admission and outpatient visits, employment status, and sickness absence associated with myasthenia gravis (MG).BackgroundMG is a rare, chronic and debilitating autoimmune neuromuscular disease characterized by muscle weakness and fatigue that leads to hallmark symptoms including ptosis, dysphagia, dyspnea and limb weakness. Nearly 10% of patients are estimated to have treatment-refractory MG.Design/MethodsData were linked from four longitudinal nationwide population-based registries in Sweden. Patients with = 1 diagnosis of MG (ICD-10 G70.0) from 01/01/2001 to 12/30/2017 were selected. Date of 1st MG diagnosis in the national patient register was designated as index date. The healthcare resource use, employment status, and sickness absence for all cause and associated with MG within 1-year post-index period were evaluated.ResultsA total of 4,339 patients with newly diagnosed MG were identified from 2001 and 2017. Mean (±SD) age at index date was 59.8 (±19.5) years; 54% were female. During the first year post-MG diagnosis, 50.6% of patients) had = 1 MG-related inpatient admission and 23.6% spent >1 month as an inpatient. Most patients (89.3%, n = 3,875) had = 1 specialist visits for MG and 16.1% had >5 visits during 1-year post-index period. 58.9% of patients had = 1 all-cause inpatient admission and 97.5% of patients used = 1 outpatient specialist services in the same period. Among patients of working age with =1-year follow-up (n = 2,006), 37.3% of them were not employed; among those in employment (n = 1,250), 44.6% reported = 1 sickness absences within 1-year post-index period.ConclusionsPatients with MG require considerable care both for MG and comorbidities over a period of years. An important sub-population of patients (e.g., those with MG crisis) may be the intensive users of both inpatient and outpatient care. Future research needs to detail treatment pattern and outcomes in this population.

Herein, we report a facile solid-state synthesis strategy for the synthesis of a three-dimensional (3D) macroporous framework molybdenum disulfide-carbide (MoS2-Mo2C) heterojunction. The MoS2-Mo2C/Mo electrode exhibits excellent HER activity with low overpotentials of 56 and 446 mV at current densities of 10 and 1000 mA cm-2, respectively, in alkaline electrolytes.

Upregulation of P2X3 receptor (P2X3R) has been strongly implicated in nociceptive signaling including bone cancer pain (BCP). The present study, using rat bone cancer model, aimed to explore the role of P2X3R in regulating rat pain behavior under the intervention of electroacupuncture (EA). The BCP model was successfully established by injection with MRMT-1 breast cancer cell into the medullary cavity of left tibia for 3 × 10(4) cells/3 μL PBS in rats as revealed by obvious bone destruction, decreased paw withdrawal thresholds (PWTs), and reduced paw withdrawal latencies (PWLs). Western blot analyses showed that P2X3R expression was significantly upregulated in ipsilateral lumbar 4–6 (L4-6) dorsal root ganglia (DRG), but the difference not seen in spinal cord dorsal horn (SCDH). With the in-depth study of P2X3R activation, we observed that intrathecal injection of P2X3R agonist α,β-meATP aggravated MRMT-1 induced BCP, while injection of P2X3R inhibitor A-317491 alleviated pain. Subsequently, we demonstrated that BCP induced mechanical allodynia and thermal hyperalgesia were attenuated after EA treatment. Under EA treatment, total P2X3R protein expression in ipsilateral DRGs was decreased, and it is worth mentioning that decreased expression of P2X3R membrane protein, which indicated that both the expression and membrane trafficking of P2X3R were inhibited by EA. The immunofluorescence assay showed that EA stimulation exerted functions by reducing the expression of P2X3R-positive cells in ipsilateral DRGs of BCP rats. Ca(2+) imaging analysis revealed that the EA stimulation decreased the percentage of α,β-meATP responsive neurons in DRGs and inhibited calcium influx. Notably, the inhibitory effect of EA on mechanical allodynia and nociceptive flinches was abolished by intrathecal injection of α,β-meATP. These findings demonstrated EA stimulation ameliorated mechanical allodynia and thermal hyperalgesia in rat model of MRMT-1-induced BCP. EA exerts analgesic effect on BCP by reducing the overexpression and functional activity of P2X3R in ipsilateral DRGs of BCP rats. Our work first demonstrates the critical and overall role of P2X3R in EA’s analgesia against peripheral sensitization of MRMT-1-induced BCP and further supports EA as a potential therapeutic option for cancer pain in clinic.

Objective: To examine the incremental mental health care resource utilization (MHRU) and barriers to receiving mental health services among adults with a major depressive episode (MDE) and suicidal ideation or behavior with intent. Methods: Data from adult participants in the 2017 National Survey on Drug Use and Health were used to identify 3 cohorts: MDE (determined by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [DSM-5] criteria) with suicidal ideation or behavior with intent (MDSI), MDE, and non-MDE. MHRU and barriers to receiving mental health services were compared among cohorts using logistic regression models. Results: The MDSI cohort had significantly higher odds (adjusted odds ratio [95% confidence interval]) of receiving mental health-related inpatient care, outpatient care, prescription medications, and any treatment versus the MDE cohort (10.2 [7.1-14.6], 2.4 [1.7-3.4], 2.4 [1.8-3.3], and 2.6 [1.8-3.7], respectively) and the non-MDE cohort (40.3 [27.3-59.5], 20.0 [14.5-27.7], 17.2 [12.9-22.9], and 19.6 [14.1-27.1], respectively). Compared to the MDE cohort, the MDSI cohort was significantly more likely to report barriers to receiving mental health services (2.6 [2.0-3.4]), with the largest differences between cohorts related to fear of negative impact (3.9 [2.8-5.4]). Additionally, 30.6% of the MDSI cohort and 47.0% of the MDE cohort did not receive any mental health treatment in the past year. Conclusions: Although respondents in the MDSI cohort reported substantially higher MHRU across all categories, they also reported greater barriers to receiving care than those in the MDE cohort. This study documents the extensive burden and unmet need in the MDSI population.

The ecological health assessment of lakes, reservoirs and wetlands can provide decision-making basis for ecosystem restoration and management. We selected 20 typical lakes, reservoirs and wetlands sampling points in Tianjin, based on physical, chemical, and biological community indicators data (zooplankton, phytoplankton, benthos, fish, large aquatic plants, riparian plants) obtained during the survey from August to September 2018. We constructed an index of ecological integrity (IEI) including physical integrity, chemical integrity, and biological integrity to evaluate their ecological health. The reference points were selected based on three aspects using standardized methods: habitat environmental quality index (QHEI), water quality status, and disturbance of human activities. The analytic hierarchy process was used to calculate the weight of the three indicators. The evaluation results of the ecological integrity of typical lakes, reservoirs and wetlands in Tianjin were finally obtained. The results showed that: 1) Among all the samples, "healthy" points accounted for 5.0%, "good" points accounted for 20.0%, "general" points accounted for 35.0%, "worse" points accounted for 30.0%, and "poor" points accounted for 10.0%. Ecological health status of typical lakes, reservoirs and wetlands in Tianjin was at a general level, with a trend that the west was better than the east with significant spatial differences. 2) Reference points were selected based on the combination of habitat score, water quality conditions, and human activity disturbance. Water quality indicators could reduce subjectivity when selecting reference points and promote the application of ecological integrity evaluation. 3) The applicability verification results showed that IEI could better characterize the health status of each point, and the discrimination efficiency was obvious, which was suitable for evaluating the ecological health of lakes, reservoirs and wetlands.对湖库湿地进行生态健康评价,可为湖库湿地生态系统修复和管理提供决策依据。本文以天津市为例,选取20个典型的湖库湿地采样点,基于2018年8—9月期间调查获取的物理、化学和生物群落指标(浮游动物、浮游植物、底栖动物、鱼类、水生大型植物、河岸带植物)数据,构建包含物理完整性、化学完整性和生物完整性在内的生态完整性指数(IEI)对采样点生态健康状况进行评价。根据栖息地环境质量(QHEI)、水质状况和人类活动干扰3方面选取参照点,采用标准化方法筛选候选指标,应用层次分析法计算各指标权重,最终得出天津市典型湖库湿地生态完整性评价结果。结果表明: 1)所有样点中,“健康”点位占5.0%,“较好”点位占20.0%,“一般”点位占35.0%,“较差”点位占30.0%,“差”点位占10.0%。天津市典型湖库湿地生态健康状况整体处于一般水平,呈现出西部优于东部的趋势,空间差异显著;2)基于栖息地评分、水质状况与人类活动干扰相结合选取参照点是可行的,依据水质指标可降低选择参照点时的主观性;3)适用性验证结果表明,IEI可较好表征各点位的健康状况,区分效率明显,适用于评价研究区湖库湿地生态健康状况。.

To observe the effect of auricular acupuncture on reduction rate of sertraline hydrochloride, and to explore the long-term efficacy of auricular acupuncture in patients with depression.Seventy-two patients with depression were randomly divided into an observation group (36 cases, 1 case dropped off) and a control group (36 cases, 2 cases dropped off). The patients in the control group were treated with conventional dosage reduction method, that is, the dosage of sertraline hydrochloride was reduced by 25% every week until the dosage was stopped completely on the premise of no aggravation of depressive symptoms. Based on the conventional dosage reduction method used in the control group, the patients in the observation group were treated with auricular acupuncture at Xin (COThe dosage of sertraline hydrochloride in the observation group was less than that in the control group after 2, 3, 4 weeks of dosage reduction and during follow-up (Auricular acupuncture could effectively reduce the dosage of sertraline hydrochloride, improve the dosage reduction rate, reduce the incidence of withdrawal syndrome and reduce the risk of long-term recurrence in patients with depression.

IntroductionUnexpected premature delivery and separation from preterm infants are common problems that parents of preterm infants must handle with. Parents of preterm infants may suffer from severe psychological distress. Family-centred care (FCC) can effectively ease parents’ psychological distress and strengthen connections between parents and their preterm infants. The purpose of this systematic review will be to systematically review and evaluate the impacts of FCC interventions on the mental health of parents of preterm infants and the parent–infant relationship.Methods and analysisThis protocol for this systematic review will be conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol. We will search databases including PubMed, Embase, The Cochrane Library, CINAHL, Web of Science, PsycINFO, Scopus and ProQuest, CNKI, SinoMed and Wanfang Data from 1 July 2012 to 1 July 2022. An additional search of OpenGrey will be conducted to identify grey literature. Randomised controlled trials related to FCC inventions for preterm infants≤37 weeks’ gestational age and their parents will be included, and the outcome measures will be parental mental health and parent–infant interaction. Two reviewers will independently conduct title and abstract screening, full-text screening, data extraction and study quality assessment. Risk of bias for the studies will be evaluated using the Cochrane Collaboration Risk of Bias V.2.0. Any disagreements will be solved by a third reviewer to reach a consensus. If appropriate, a meta-analysis will be conducted to assess the effect of FCC on parental mental health and parent–infant relationship.Ethics and disseminationResearch ethics approval will not be required for this review since it will not involve the collection of primary data and will only use published literature. The results will be disseminated in a peer-reviewed journal through publication or by presentation at relevant academic conference.PROSPERO registration numberCRD42022299203.

Silicosis is an occupational disease caused by inhalation of silica dust, which is hallmarked by progressive pulmonary fibrosis associated with poor prognosis. Wnt/β-catenin signaling is implicated in the development of fibrosis and is a therapeutic target for fibrotic diseases. Previous clinical studies of patients with pneumoconiosis, including silicosis, revealed an increased concentration of circulating WNT3A and DKK1 proteins and inflammatory cells in bronchoalveolar lavage compared with healthy subjects. The present study evaluated the effects of adenovirus-mediated transduction of

Background and aims We previously demonstrated that cancer-associated fibroblasts (CAFs) promote tumor growth via recruiting of myeloid-derived suppressor cells (MDSCs). 5-lipoxygenase (5-LO) is highly expressed in myeloid cells and critical for synthesizing leukotriene B4 (LTB4), which is involved in tumor progression via acting its receptor Leukotriene B4 receptor type 2 (BLT2). In this study, we investigated whether and how CAFs regulate MDSC function to enhance cancer stemness, the driving force of the cancer aggressiveness and chemotherapy refractoriness, in highly desmoplastic intrahepatic cholangiocarcinoma (ICC). Approach and results RNA-sequencing analysis revealed enriched metabolic pathways but decreased inflammatory pathways in cancer MDSCs compared with blood MDSCs from ICC patients. Co-injection of ICC patient-derived CAFs promoted cancer stemness in an orthotopic ICC model, which was blunted by MDSC depletion. Conditioned media (CM) from CAF-educated MDSCs drastically promoted tumorsphere formation efficiency and stemness marker gene expression in ICC cells. CAF-CM stimulation increased expression and activity of 5-LO in MDSCs while 5-LO inhibitor impaired the stemness-enhancing capacity of MDSCs in vitro and in vivo. Furthermore, IL-6 and IL-33 mainly expressed by CAFs mediated hyperactivated 5-LO metabolism in MDSCs. We identify the LTB4-BLT2 axis as the critical downstream metabolite signaling of 5-LO in promoting cancer stemness, as treatment with LTB4 that were elevated in CAF-educated MDSCs or blockade of BLT2 that was preferentially expressed in stem-like ICC cells significantly reduced stemness-enhancing effects of CAF-educated MDSCs. Finally, BLT2 blockade augmented chemotherapeutic efficacy in ICC patient derived-xenograft (PDX) models. Conclusions Our study reveals a previously unrecognized role for CAFs in orchestrating the optimal cancer stemness-enhancing microenvironment by educating MDSCs and suggests 5-LO/LTB4-BLT2 axis as promising therapeutic targets for ICC chemoresistance by targeting cancer stemness.

Common spatial pattern (CSP) is one of the most popular feature extraction techniques that performs well in the field of brain-computer interface (BCI). However, the classical CSP based on the squared Frobenious norm is known to be sensitive to noise and prone to overfitting. In recent years, efforts have been made to solve the problem of robust and sparse modeling. Therefore, we describe the formulation of a CSP criterion by using the L21-norm and add the L21-norm regularization term. The regularized version of the L21-norm-based common spatial pattern is termed RCSP-L21 in this paper. An iterative algorithm is designed to obtain the spatial filters of the regularized objective function. Experimental results on EEG dataset IIa of BCI Competition IV verify the effectiveness of our new method.